SAS for Biochemistry (BIO 024) Module 9.pdf

Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: _____________________________________________________________ Class number: _______ Section: ____________...

Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule:_____________________________________ Date:________________ Lesson title: LIPID METABOLISM Materials: Lesson Objectives: by the end of this module, you should Pen, SAS be able to … References: 1. Identify the metabolic pathways and the intermediate ▪ stoker, H. S. (2017).Biochemistry (3rd ed.). (M. compounds of lipid metabolism. Finch, Ed.) Belmont CA, USA, 2. Explain the importance of the metabolic processes of ▪ Ferrier, D. (2017). Lippincott's Illustrated lipid metabolism in relation to its clinical significance. Biochemistry (7 ed.). Lippincott Williams & Wilkins Productivity Tip: Today, I want you to get a tape measure and practice less to no carbohydrate but fat rich diet while having short physical exercises. Now, wonder how you provided yourself with energy even consuming less to no carbohydrates. You might want to make a quick search on keto diet. Measure your waistline again after few days to see if there’s a difference. Somehow, this module will help you understand how you generate energy and consume it from lipid sources. A. LESSON PREVIEW/REVIEW 1) Introduction (1 min) Obesity is a disorder of body weight regulatory systems characterized by an accumulation of excess body fat, results when energy (caloric) intake exceeds energy expenditure. Knowing such that excess energy derived from carbohydrates and proteins beyond normal daily needs however, if not mobilized when not used, is stored in lipid molecules (adipose tissue). Though, in primitive societies, in which daily life required a high level of physical activity and food was only available intermittently, a genetic tendency favoring storage of excess calories as fat may have had a survival value. Today, however, the sedentary lifestyle and abundance and wide variety of palatable, inexpensive foods in industrialized societies has undoubtedly contributed to an obesity epidemic. The body mass index (BMI) is easy to determine and highly correlated to body fat; overweight (BMI ≥ 25 kg/m2 ) and obese (BMI > 30 kg/m2 ). The anatomic distribution of body fat has a major influence on associated health risks. Excess fat located in the central abdominal area is associated with greater risk for hypertension, insulin resistance, diabetes, dyslipidemia,, coronary heart disease, arthritis and cancer. A person’s weight is determined by genetic and environmental factors. Particularly alarming is the explosion of obesity in children and adolescents, which has shown a three-fold increase in prevalence over the last two decades. Obesity has increased globally. In fact, by some estimates, there are more obese than undernourished individuals worldwide. In this module, it is by far our concern to understand how are lipids playing extremely important role in cellular metabolism as they represent as the source of an energy-rich fuel stored in large amounts in adipose (fat) tissue from digestion to metabolic pathways. Because 98% of total dietary lipids are triacylglycerols (fats and oils, this module focuses on triacylglycerol metabolism. This will also include diagrammatic representation of the relationship of lipid and carbohydrate metabolism in relation to the Lippincott, 7th ed This document is the property of PHINMA EDUCATION Page |1  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule:_____________________________________ Date:________________ development of diabetes as one of the major contributor of cardiovascular diseases. (Stoker, 3rd ed) 2) Activity 1: What I Know Chart, part 1 (3 mins) Instructions: "In this chart, reflect on what you know now. Do not worry if you are sure or not sure of your answers. This activity simply serves to get you started on thinking about our topic. Answer only the first column, "What I know" based on the question of the second column. Leave the third column "What I learned" blank at this time. What I Know Questions: What I Learned (Activity 4) 1.What do you think is the mechanism of relationship between lipids and the development of diabetes? 2.With our fat reserves, how many days you think we can survive starvation given enough amount of water? 3.What is your estimate on the amount of energy provided by fat (TAG) compared to sugar (glucose)? B.MAIN LESSON: Activity 2: Content notes (70 min). Instructions: Make your own side notes upon looking at this module. It would help if you also watch videos to get a full recap of the metabolic pathways we are about to discuss. Digestion and Absorption of Lipids (Stoker, 3rd ed.) This document is the property of PHINMA EDUCATION Page |2  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule:_____________________________________ Date:________________ Nice to know! Like all lipids, triacylglycerols (TAGs) are insoluble in water. Hence water-based salivary enzymes in the mouth have little effect on them. The major change that The saliva of infants contains a lipase TAGs undergo in the stomach is physical rather than chemical. The churning action that can hydrolyze TAGs, so digestion of the stomach breaks up triacylglycerol materials into small globules, or droplets, begins in the mouth for nursing which float as a layer above the other components of swallowed food. The resulting infants. Because mother’s milk is material is called chyme. Chyme is a thick semi-liquid material made up of partially already a lipid-in-water emulsion, digested food and gastric secretions (hydrochloric acid and several enzymes). emulsifications by stomach churning High-fat foods remain in the stomach longer than low-fat foods. The conversion of is a much less important factor in an high-fat materials into chyme takes longer than the breakup of low-fat. materials. infant’s processing of fat. Mother’s This is why a high-fat meal causes a person to feel “full” for a longer period of time. milk also contains a lipase that Lipid digestion also begins in the stomach. Under the action of gastric lipase supplements the action of the salivary enzymes, hydrolysis of TAGs occurs. Normally, about 10% of TAGs undergo lipases the infant itself produces. After hydrolysis in the stomach, but regular consumption of a high-fat diet can induce the weaning, infants cease to produce production of higher levels of gastric lipases. The arrival of chyme from the stomach salivary lipases. triggers in the small intestine, through the action of the hormone cholecystokinin, the release of bile stored in the gallbladder. The bile, which contains no enzymes, acts as an emulsifier.Colloid particle formation through bile emulsifi cation “solubilizes” the triacylglycerol globules, and digestion of the TAGs resumes. The major enzymes involved at this point are the pancreatic lipases, which hydrolyze ester linkages between the glycerol and fatty acid units of the TAGs. Complete hydrolysis does not usually occur; only two of the three fatty acid units are liberated, producing a monoacylglycerol and two free fatty acids. Occasionally, enzymes remove all three fatty acid units, leaving a free glycerol molecule. With the help of bile, the free fatty acids and monoacylglycerols produced from hydrolysis are combined into tiny spherical droplets called micelles. A fatty acid micelle is a micelle in which fatty acids and/or monoacylglycerols and some bile are present. Fatty acid micelles are very small compared to the original triacylglycerol globules, which contain thousands of triacylglycerol molecules. Micelles, containing free fatty acid and monoacylglycerol components, are small enough to be readily absorbed through the membranes of intestinal cells. Within the intestinal cells, a “repackaging” occurs in which the free fatty acids and monoacylglycerols are reassembled into triacylglycerols. The newly formed triacylglycerols are then combined with membrane lipids (phospholipids and cholesterol) and water-soluble proteins to produce a type of lipoprotein called a chylomicron. A chylomicron is a lipoprotein that transports triacylglycerols from intestinal cells, via the lymphatic system, to the bloodstream. Triacylglycerols constitute 95% of the core lipids present in a chylomicron. Chylomicrons are too large to pass through capillary walls directly into the bloodstream. Consequently, delivery of the chylomicrons to the bloodstream is accomplished through the body’s lymphatic system. Chylomicrons enter the lymphatic system through tiny lymphatic vessels in the intestinal lining. They enter the bloodstream through the thoracic duct (a large lymphatic vessel just below the collarbone), where the fluid of the lymphatic system flows into a vein, joining the bloodstream. Once the chylomicrons reach the bloodstream, the TAGs they carry are again hydrolyzed to produce glycerol and free fatty acids. TAG release from chylomicrons and their ensuing hydrolysis is mediated by lipoprotein lipases. These enzymes are located on the lining of blood vessels in muscle and other tissues that use fatty acids for fuel and in fat synthesis. The fatty acid and glycerol hydrolysis products from TAG hydrolysis are absorbed by the cells of the body and are either broken down to acetyl CoA for energy or stored as lipids (they are again repackaged as TAGs). This document is the property of PHINMA EDUCATION Page |3  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule:_____________________________________ Date:________________ SUMMARY: Key concept map for metabolism of dietary lipids. apo = apolipoprotein; TAGs = triacylglycerols. Lippincott, 7th ed This document is the property of PHINMA EDUCATION Page |4  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule:_____________________________________ Date:________________ Triacylglycerol Storage and Mobilization An adipocyte is a triacylglycerol-storing cell. Adipose tissue is tissue that contains large numbers of adipocyte cells, located primarily directly beneath the skin (subcutaneous), particularly in the abdominal region, and in areas around vital organs. Functions of Adipose tissue: ▪ storage location for the chemical energy inherent in TAGs, ▪ subcutaneous adipose tissue as an insulator ▪ provides organs with protection against physical shock. Adipose cells are among the largest cells in the body. They differ from other cells in that most of the cytoplasm has been replaced with a large triacylglycerol droplet (Figure 25.4). This droplet accounts for nearly the entire volume of the cell. As newly formed TAGs are imported into an adipose cell, they form small droplets at the periphery of the cell that later merge with the large central droplet. Use of the TAGs stored in adipose tissue for energy production is triggered by several hormones, including epinephrine and glucagon. Hormonal interaction with adipose cell membrane receptors stimulates production of cAMP from ATP inside the adipose cell. In a series of enzymatic reactions, the cAMP activates hormone- sensitive lipase (HSL) through phosphorylation. HSL is the lipase needed for triacylglycerol hydrolysis, a prerequisite for fatty acids to enter the bloodstream from an adipose cell. This cAMP activation process is illustrated in Figure 25.5. The overall process of tapping the body’s triacylglycerol energy reserves (adipose tissue) for energy is called triacylglycerol mobilization. Triacylglycerol mobilization is the hydrolysis of triacylglycerols stored in adipose tissue, followed by release into the bloodstream of the fatty acids and glycerol so produced. Triacylglycerol mobilization is an ongoing process. On the average, about 10% of the TAGs in adipose tissue are replaced daily by new triacylglycerol molecules. Triacylglycerol energy reserves (fat reserves) are the human body’s major source of stored energy. Energy reserves associated with protein, glycogen, and glucose are small to very small when compared to fat reserves. Table 25.1 shows relative amounts of stored energy associated with the various types of energy reserves present in the human body This document is the property of PHINMA EDUCATION Page |5  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule:_____________________________________ Date:________________ Nice to know! Triacylglycerol reserves would enable the average person to survive starvation for about 30 days, given suffi cient water. Glycogen reserves (stored glucose) would be depleted within 1 day. GLYCEROL METABOLISM During triacylglycerol mobilization, one molecule of glycerol is produced for each triacylglycerol completely hydrolyzed. After entering the bloodstream, glycerol travels to the liver or kidneys, where it is converted, in a two-step process, to dihydroxyacetone phosphate. 1st step: phosphorylation 2nd step: glycerol’s secondary of a primary hydroxyl alcohol group (C-2) is oxidized group of the glycerol to form ketone. Pathways for production of glycerol 3-phosphate in liver and adipose tissue. (Note: glycerol 3-phosphate can also be generated by glyceroneogenesis) ADP =adenosine diphosphate Lippincott, 7th ed Dihydroxyacetone phosphate is an intermediate in both glycolysis and gluconeogenesis. It can be converted to pyruvate, then acetyl CoA, and finally carbon dioxide, or it can be used to form glucose. Dihydroxyacetone phosphate formation from glycerol represents the first of several situations we will consider wherein carbohydrate and lipid metabolism are connected. (see diagram of interrelationship next page). This document is the property of PHINMA EDUCATION Page |6  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule:_____________________________________ Date:________________ This document is the property of PHINMA EDUCATION Page |7  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule:_____________________________________ Date:________________ Oxidation of Fatty Acids There are three parts to the process by which fatty acids are broken down to obtain energy. 1st: Activation fatty acid must be activated by boding to coenzyme A Occur at the outer mitochondrial membrane. Reactants are the fatty acid, coenzyme A, and a molecule of ATP. ▪ Acyl CoA- the activated fatty acid–CoA molecule refers to a randomlength fatty acid carbon chain that is covalently bonded to coenzyme A. ▪ Acetyl CoA- refers to a two-carbon chain covalently bonded to coenzyme A. fatty acid must be transported into mitochondrial matrix 2nd: Transport shuttle mechanism Acyl CoA is too large to pass through the inner mitochondrial membrane to the mitochondrial matrix, where the enzymes needed for fatty acid oxidation are located. A shuttle mechanism involving the molecule carnitine effects the entry of acyl CoA into the matrix (Figure 25.6). The acyl group is transferred to a carnitine molecule, which carries it through the membrane. The acyl group is then transferred from the carnitine back to a CoA molecule. This document is the property of PHINMA EDUCATION Page |8  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule:_____________________________________ Date:________________ fatty acid must be repeatedy oxidized,cycling through a 3rd:β-oxidation series of four reactions, to produce CoA,FADH2, and NADH. In the mitochondrial matrix, a sequence of four reactions repeatedly cleaves two carbon units from the carboxyl end of the acyl CoA molecule. This is called β-oxidation pathway because the second carbon from the carboxyl end of the chain, the beta carbon, is the carbon atom that is oxidized. The β-oxidation pathway is a repetitive series of four biochemical reactions that degrades acyl CoA to acetyl CoA by removing two carbon atoms at a time, with FADH2 and NADH also being produced. Each repetition of the four-reaction sequence generates an acetyl CoA molecule and an acyl CoA molecule that has two fewer carbon atoms. For a SATURATED (full of single bond) fatty acid Details about Steps 1–4 of the b-oxidation pathway follow. Step 1: First Dehydrogenation. Hydrogen atoms are removed from the α and β carbons, creating a double bond between these two carbon atoms. FAD is the oxidizing agent, and a FADH2 molecule is a product. The enzyme involved is stereospecific in that only trans double bonds are produced. Step 2: Hydration. A molecule of water is added across the trans double bond, producing a secondary alcohol at the b-carbon position. Again, the enzyme involved is stereospecific in that only the L- hydroxy isomer is produced from the trans double bond. The enzyme involved in this hydration will also hydrate a cis double bond, but the product then is the D isomer. D isomer formation is of importance when considering how unsaturated fatty acids are oxidized, a topic discussed later in this section Step 3: Second Dehydrogenation. Removal of two hydrogen atoms converts the b-hydroxy group to a keto group, with NAD+ serving as the oxidizing agent. The required enzyme exhibits absolute stereospecifi city for the L isomer. It is now apparent why the name for this series of reactions is the b-oxidation pathway. The b-carbon atom has been oxidized from a -CH2- group to a ketone group. This document is the property of PHINMA EDUCATION Page |9  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule:_____________________________________ Date:________________ Step 4: Thiolysis. The fatty acid carbon chain is broken between the a and b carbons by reaction with a coenzyme A molecule. The result is an acetyl CoA molecule and a new acyl CoA molecule that is shorter by two carbon atoms than its predecessor. The new acyl CoA molecule (now shorter by two carbons) is recycled through the same set of four reactions again. This yields another acetyl CoA, a two- carbonshorter new acyl CoA, FADH2, and NADH. Recycling occurs again and again, until the entire fatty acid is converted to acetyl CoA. Thus the fatty acid carbon chain is sequentially degraded, two carbons at a time. SUMMARY The fatty acids normally found in dietary triacylglycerols contain an even number of carbon atoms. Thus the number of acetyl CoA molecules produced in the β- oxidation pathway is equal to half the number of carbon atoms in the fatty acid. The number of repetitions of the b- oxidation pathway that are needed to produce the acetyl CoA is always one less than the number of acetyl CoA molecules produced because the last repetition produces two acetyl CoA molecules as a C4 unit splits into two C2 units. C18 fatty acid → 9 acety1 CoA (8 repetitive sequences) C14 fatty acid → 7 acety1 CoA (6 repetitive sequences) This document is the property of PHINMA EDUCATION P a g e | 10  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule:_____________________________________ Date:________________ UNSATURATED FATTY ACIDS: Their oxidation through the β-oxidation pathway requires two additional enzymes besides those needed for oxidation of saturated fatty acids. These two—an epimerase that can change a D configuration to an L configuration and a cis–trans isomerase—are needed for two reasons. First, the double bonds in naturally occurring unsaturated fatty acids are nearly always cis double bonds, which yield on hydration a D-hydroxy product rather than the L-hydroxy product needed for Step 3 of the pathway. The epimerase enzyme effects a confi guration change from the D form to the L form. Second, the double bonds in naturally occurring unsaturated fatty acids often occupy odd- numbered positions. The hydratase in Step 2 of the pathway can effect hydration of only an even-numbered double bond. The cis– trans isomerase produces a trans-(2,3) double bond from a cis-(3,4) double bond. The Step 2 hydratase can then work on the trans-(2,3) double bond in the normal fashion. ATP Production from Fatty Acid Oxidation Figure 25.7 shows that for each four-reaction sequence except the last one, one FADH2 molecule, one NADH molecule, and one acetyl CoA molecule are produced. In the final four-reaction sequence, two acetyl CoA molecules are produced in addition to the FADH2 and NADH molecules. Eight repetitions of the b-oxidation pathway are required for the oxidation of stearic acid, an 18-carbon acid. These eight repetitions of the pathway produce 9 acetyl CoA molecules, 8 FADH2 molecules, and 8 NADH molecules. Further processing of these products through the common metabolic pathway (citric acid cycle, electron transport chain, and oxidative phosphorylation) leads to ATP production as follows: This gross production of 122 ATP must be decreased by the ATP needed to activate the fatty acid before it enters the b- oxidation pathway. The activation consumes two high-energy phosphate bonds of an ATP molecule. For accounting purposes, this is equivalent to hydrolyzing 2 ATP molecules to ADP. Thus the net ATP production from oxidation of stearic acid is 120 ATP (122 minus 2). Nice to know! ATP COMPARISON:. fatty acid glucose (6C) vs oxidation 4x > stearic acid (18C) complete glucose oxidation This document is the property of PHINMA EDUCATION P a g e | 11  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule:_____________________________________ Date:________________ lipids are 33% more efficient than carbohydrates for energy storage w/ equal no. of carbons On an equal-mass basis, fatty acids produce 2.5 times as much energy per gram as carbohydrates (glucose); means that, in terms of calories consumed, the fatty acids “do 2.5 times as much damage” to a person on a diet. GENERALIZATIONS ABOUT “FUEL” USE: (see next page) Skeletal muscle uses glucose Cardiac muscle depends first (from glycogen) when in an on fatty acids and secondarily active state. In a resting state, on ketone bodies, glucose, and it uses fatty acids. lactate. Brain function is maintained by glucose and ketone bodies. The liver uses fatty acids as Fatty acids cannot cross the the preferred fuel. blood–brain barrier and thus are unavailable. Ketone Bodies Ordinarily, when there is adequate balance between lipid and carbohydrate metabolism, most of the acetyl CoA produced from the β-oxidation pathway is further processed through the citric acid cycle. ▪ The first step of the citric acid cycle involves the reaction between oxaloacetate and acetyl CoA. ▪ Sufficient oxaloacetate must be present for the acetyl CoA to react with. ▪ Oxaloacetate concentration depends on pyruvate produced from glycolysis; pyruvate can be converted to oxaloacetate by pyruvate carboxylase. ▪ Body conditions upset the lipid–carbohydrate balance required for acetyl CoA generated by fatty acids to be processed by the citric acid cycle. Under these conditions, the problem of inadequate oxaloacetate supplies arises, which is compounded by the body’s using oxaloacetate that is present to produce glucose through gluconeogenesis (2) (3) (1) diabetic conditions in which the prolonged fasting conditions, dietary intake high in fat and low in body cannot adequately process including starvation, where carbohydrates glucose even though it is glycogen supplies are exhausted. present;& Intertissue relationships during starvation. This document is the property of PHINMA EDUCATION P a g e | 12  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule:_____________________________________ Date:________________ Lippincott, 7th ed This document is the property of PHINMA EDUCATION P a g e | 13  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule:_____________________________________ Date:________________ This document is the property of PHINMA EDUCATION P a g e | 14 Lippincott, 7th ed  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule:_____________________________________ Date:________________ Question! Answer! Well, the excess What happens when acetyl CoA is diverted to the oxaloacetate supplies are too formation of ketone bodies low for all acetyl CoA present to be processed through the citric acid cycle? KETONE BODY! Is one of three substances (acetoacetate, β- hydroxybutyrate, and acetone) produced from acetyl CoA when an excess of acetyl CoA from fatty acid degradation accumulates because of triacylglycerol–carbohydrate metabolic imbalances. Uses: serve as sources of energy for various tissues and are very important energy sources in heart muscle and the renal cortex. Ketogenesis Ketogenesis is the metabolic pathway by which ketone bodies are synthesized from acetyl CoA. Items to consider about this process prior to looking at the actual steps in this four-step process are: 1. The primary site for the process is liver mitochondria. 2. The first ketone body to be produced is acetoacetate. This production occurs in Step 3 of ketogenesis. 3. Some of the acetoacetate produced in Step 3 is converted to the second ketone body, β-hydroxybutyrate, in Step 4 of ketogenesis. 4. The acetoacetate and β-hydroxybutyrate synthesized by ketogenesis in the liver are released to the bloodstream where acetone, the third ketone body, is produced. 5. Acetoacetate is somewhat unstable and can spontaneously or enzymatically lose its carboxyl group to form acetone. Thus the ketone body acetone is not actually a product of the metabolic pathway ketogenesis. 6. The ketone body acetone present in the bloodstream is a volatile substance that is mainly excreted by exhalation. Its sweet odor is detectible in the breath of a diabetic. 7. The amount of acetone present is usually small compared to the concentrations of the other two ketone bodies. Figure 25.8 Ketogenesis involves the production of Reaction steps in the process of ketogenesis are: ketone bodies from acetyl CoA This document is the property of PHINMA EDUCATION P a g e | 15  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule:_____________________________________ Date:________________ Step 1: First condensation. Two acetyl CoA molecules combine to produce acetoacetyl CoA, a reversal of the last step of the b- oxidation pathway via a condensation reaction. Step 2: Second condensation. Acetoacetyl CoA reacts with a third acetyl CoA and water to produce 3-hydroxy-3-methylglutaryl CoA (HMG- CoA) and CoA-SH. Step 3: Chain cleavage. HMG-CoA is cleaved to acetyl CoA and acetoacetate. Step 4: Hydrogenation. Acetoacetate is reduced to β-hydroxybutyrate. The reducing agent is NADH. For acetoacetate to be used as a fuel—it must first be activated. Acetoacetate is activated by transfer of a CoA group from succinyl CoA (a citric acid cycle intermediate). The resulting acetoacetyl CoA is then cleaved to give two acetyl CoA molecules that can enter the Nice to know! citric acid cycle Heart muscle and the renal cortex use acetoacetate in preference to glucose. The brain adapts to the utilization of acetoacetate with starvation or diabetes. 75% of the fuel needs of the brain are obtained This document is the property of PHINMA EDUCATION P a gprolonged from acetoacetate during e | 16 starvation.  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule:_____________________________________ Date:________________ Ketosis Under normal metabolic conditions (an appropriate glucose–fatty acid balance), the concentration of ketone bodies in the blood is very low—about 1 mg/100 mL. Abnormal metabolic conditions, produce elevated blood ketone levels, levels 50– 100 times greater than normal. ▪ Ketonemia- excess accumulation of ketone bodies in blood (20 mg/100 mL) is called At a level of 70 mg/100 mL, ▪ Ketonuria- the renal threshold is exceeded and ketone bodies are excreted in the urine, ▪ Ketosis –the overall accumulation of ketone bodies in the blood and urine. Ketosis is often detectable by the smell of acetone on a person’s breath; acetone is very volatile and is excreted through the lungs. o Mild ketosis - result of such dieting include headache, dry mouth, and sometimes acetone-smelling breath. True for fasting situation. o Ketoacidosis – extremely serious ketosis that can develop to persons with uncontrolled Type 1 diabetes. Two of the three ketone bodies— acetoacetate and b-hydroxybutyrate—are acids; a carboxyl group is present in their structure. At elevated levels, the presence of these two ketone bodies can cause a significant decrease in blood pH. This change in blood acidity, if left untreated, leads to heavy breathing (acidic blood carries less oxygen) and increased urine output that can lead to dehydration or ultimately can cause coma and death. ▪ Aka metabolic acidosis to distinguish it from respiratory acidosis, which is not linked to ketone bodies Biosynthesis of Fatty Acids: Lipogenesis Lipogenesis is the metabolic pathway by which fatty acids are synthesized from acetyl CoA. As was the case for the opposing processes of glycolysis and gluconeogenesis, lipogenesis is not simply a reversal of the steps for degradation of fatty acids (the β-oxidation pathway). In general, fatty acid biosynthesis (lipogenesis) occurs any time dietary intake provides more nutrients than are needed for energy requirements. The primary lipogenesis sites are the liver, adipose tissue, and mammary glands. The mammary glands show increased synthetic activity during periods of lactation. Differences between the synthesis and degradation of fatty acids: Differences in β-oxidation pathway: Degradation of fatty Lipogenesis: synthesis of fatty acids features acids 1.Cell site cell cytosol mitochondrial matrix 2.Enzymes are collected into a multienzyme complex called are not physically associated, so the fatty acid synthase making the steps close reaction steps are independent. together. 3.Intermediate bonded to ACP (acyl carrier protein) CoA carrier 4.Dependency to reducing agent NADPH oxidizing agents FAD and NAD+ 5.Sources of 2 acetyl CoA is used to form malonyl ACP, which CoA derivatives are involved in all steps carbon units becomes the carrier of the two carbon units The Citrate–Malate Shuttle System Acetyl CoA is the starting material for lipogenesis. Because acetyl CoA is generated in mitochondria and lipogenesis occurs in the cytosol, the acetyl CoA must first be transported to the cytosol. It exits the mitochondria through a transport system that involves citrate ion. The outer mitochondrial matrix is freely permeable to acetyl CoA, as well as many other substances such as citrate, malate, and pyruvate. The inner mitochondrial membrane, however, is not permeable to acetyl CoA. An indirect shuttle system involving citrate solves this problem. See Figure 25.10. Mitochondrial acetyl CoA reacts with oxaloacetate (the first step of the citric acid cycle) to produce citrate, which is then transported through the inner mitochondrial membrane by a citrate transporter (a membrane protein structure). This document is the property of PHINMA EDUCATION P a g e | 17  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule:_____________________________________ Date:________________ Once in the cytosol, the citrate undergoes the reverse reaction to its formation to regenerate the acetyl CoA and oxaloacetate, with ATP involved in the process. The acetyl CoA so generated becomes the “fuel” for lipogenesis; the oxaloacetate so generated reacts further to produce malate, in an NADH dependent change. The malate reenters the mitochondrial matrix through a malate transporter and is then converted to oxaloacetate, which can then react with another acetyl CoA molecule to form citrate and the shuttle process repeats itself. ACP Complex Formation Studies show that all intermediates in fatty acid biosynthesis (lipogenesis) are bound to acyl carrier proteins (ACP-SH) rather than coenzyme A (CoA-SH). This applies even to the C2 acetyl group. An acyl carrier protein can be regarded as a “giant coenzyme A molecule.” Involved in the ACP structure are the 2-ethanethiol and pantothenic acid components present in CoA-SH, which are attached to a polypeptide chain containing 77 amino acid residues. Two simple ACP complexes are needed to start the lipogenesis process. They are acetyl ACP, a C2-ACP, and malonyl ACP, a C3-ACP. Additional malonyl ACP molecules are needed as the lipogenesis process proceeds. Cytosolic acetyl CoA is the starting material for the production of both of these simple ACP complexes. Acetyl ACP is produced by the direct reaction of acetyl CoA with an ACP molecule. The reaction to produce malonyl ACP requires two steps. The first step is a carboxylation reaction with ATP involvement This document is the property of PHINMA EDUCATION P a g e | 18  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule:_____________________________________ Date:________________ This reaction occurs only when cellular ATP levels are high. It is catalyzed by acetyl CoA carboxylase complex, which requires both Mn2+ ion and the B vitamin biotin for its activity. The malonyl CoA so produced then reacts with ACP to produce malonyl ACP. Chain Elongation Four reactions that occur in a cyclic pattern within the multienzyme fatty acid synthase complex constitute the chain elongation process used for fatty acid synthesis. The reactions of the first turn of the cycle, in general terms, are shown in Figure 25.11. Specific details about this series of reactions This document is the property of PHINMA EDUCATION P a g e | 19  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule:_____________________________________ Date:________________ Step 1: Condensation. Acetyl ACP and malonyl ACP condense together to form acetoacetyl ACP. Step 2: First hydrogenation. The keto group of the acetoacetyl complex, which involves the b- carbon atom, is reduced to the corresponding alcohol by NADPH. Step 3: Dehydration. The alcohol produced in Step 2 is dehydrated to introduce a double bond into the molecule (between the a and b carbons). Step 4: Second hydrogenation. The double bond introduced in Step 3 is converted to a single bond through hydrogenation. As in Step 2, NADPH is the reducing agent. Further cycles of the preceding four- step process convert the four- carbon acyl group to a six-carbon acyl group, then to an eight-carbon acyl group, and so on (Figure 25.12). Elongation of the acyl group chain through this procedure, which is tied to the fatty acid synthase complex, stops upon formation of the C16 acyl group (palmitic acid). Different enzyme systems and different cellular locations are required for elongation of the chain beyond C16 and for introduction of double bonds into the acyl group (unsaturated fatty acids) This document is the property of PHINMA EDUCATION P a g e | 20  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule:_____________________________________ Date:________________ Unsaturated Fatty Acid Biosynthesis Production of unsaturated fatty acids (insertion of double bonds) requires molecular oxygen (O2). In an oxidation step, hydrogen is removed and combined with the O2 to form water. In humans and animals, enzymes can introduce double bonds only between C-4 and C-5 and between C-9 and C-10. Thus the important unsaturated fatty acids linoleic (C18 with C-9 and C-12 double bonds) and linolenic (C18 with C-9, C-12, and C-15 double bonds) cannot be biosynthesized. They must be obtained from the diet. (Plants have the enzymes necessary to synthesize these acids.) Acids such as linoleic and linolenic, which cannot be synthesized by the body but are necessary for its proper functioning, are called essential fatty acids. Lipogenesis can be used to convert glucose to fatty acids via acetyl CoA. The reverse process, conversion of fatty acids to glucose, is not possible within the human body. Fatty acids can be broken down to acetyl CoA, but there is no enzyme present for the conversion of acetyl CoA to pyruvate or oxaloacetate, starting materials for gluconeogenesis. Plants and some bacteria do possess the needed enzymes and thus can convert fatty acids to carbohydrates. Relationships Between Lipogenesis and Citric Acid Cycle Intermediates The intermediates in the last four steps of the citric acid cycle are all C4 molecules.In the fi rst cycle of the four repetitive reactions in lipogenesis, all of the carbon chains attached to ACP are C4 chains. Several relationships exist between these two sets of C4 entities. The last four intermediates of the citric acid cycle bear the following relationship to each other Saturated C4 diacid → unsaturated C4 diacid → hydroxy C4 diacid → keto C4 diacid The intermediate C4 carbon chains of lipogenesis bear the following relationship to each other Keto C4 monoacid → hydroxy C4 monoacid → unsaturated C4 monoacid → saturated C4 monoacid Note two important contrasts in these compound sequences: 1.The citric acid intermediates involve C4 diacids, and the lipogenesis intermediates involve C4 monoacids. 2.The order in which the various acid derivative types are encountered in lipogenesis is the reverse of the order in which they are encountered in the citric acid cycle Figure 25.13 Structural relationships between C4 citric acid cycle intermediates and C4 lipogenesis intermediates. C4 citric acid cycle intermediates are diacid derivatives, and C4 lipogenesis intermediates are monoacid derivatives. The same derivative types are This document is the property of PHINMA EDUCATION present in both series of intermediates. P a g e | 21  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule:_____________________________________ Date:________________ Fate of Fatty Acid Generated Acetyl CoA What happens to the acetyl-CoA obtained from fatty acid oxidation? Several different options are available for its use. These options include the following: 1. The acetyl-CoA can be further processed through the common metabolic pathway (CAC, ETC, and oxidative phosphorylation) to obtain ATP. 2. The acetyl-CoA can undergo conversion to ketone bodies. Such ketone bodies can be reconverted, when needed, back to acetyl-CoA, which can then be processed for ATP production. 3. The acetyl-CoA can be stored in the body in the form of triacylglycerols by reconverting via lipogenesis the acetyl-CoA to fatty acids that are then converted to triacylglycerols. 4. The acetyl-CoA can be used as the starting material for the production of lipids other than fatty acids that the body needs. A specific example of such “other lipid” production is the biosynthesis of cholesterol. Cholesterol is a necessary component of cell membranes. It is also the precursor for bile salts, sex hormones, and adrenal hormones. The biosynthesis of cholesterol, a C27 molecule, occurs primarily in the liver. Biosynthesis of cholesterol consumes 18 molecules of acetyl CoA and involves at least 27 separate enzymatic steps. The rate-determining step in the formation of cholesterol occurs early in its biosynthesis. It involves the formation of the C6 intermediate mevalonate; in a multistep sequence, three acetyl CoA molecules are condensed together to produce this C6 species This document is the property of PHINMA EDUCATION P a g e7th |ed22 Lippincott,  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule:_____________________________________ Date:________________ 5. It is also important to note what cannot happen to the acetyl CoA obtained from fatty acid oxidation. In humans and animals, it cannot be used for the net synthesis of glucose. Good to know! ▪ Pyruvate or oxaloacetate is the needed starting material for glucose production via gluconeogenesis. ▪ Humans and animals do not possess the enzymes needed to convert acetyl CoA to pyruvate. (By contrast, plants do contain the two additional enzymes needed.) ▪ Pyruvate can be converted to acetyl CoA in a reaction sequence that is irreversible. ▪ Acetyl CoA cannot be converted to pyruvate. ▪ In Step 1 of gluconeogenesis, pyruvate is converted to oxaloacetate ▪ Oxaloacetate is also produced in the last reaction of the citric acid cycle. However, use of such oxaloacetate in glucose production cannot lead to a net increase in glucose. In each round of the citric acid cycle, two carbon atoms enter. the cycle (as acetyl CoA) and two carbon atoms leave the cycle (as CO 2). Thus there is no gain in carbon atoms in a turn of the cycle. The oxaloacetate produced in the last step of the cycle is not newly formed oxaloacetate but, rather, regenerated oxaloacetate; in Step 1 of the citric acid cycle oxaloacetate is consumed, and in Step 8 it is regenerated. Thus no net increase in oxaloacetate production occurs during the citric acid cycle because there is no net increase in carbon atoms processed; as a result, no net increase in glucose production can occur using oxaloacetate. B Vitamins and Lipid Metabolism Collectively, for the processes of β- oxidation, ketogenesis, and lipogenesis, as is shown in Figure 25.15, four of the eight B vitamins are needed. These are: niacin (as NAD+, NADH, and NADPH), riboflavin (as FAD), pantothenic acid (as CoA, acetyl-CoA, and ACP), and biotin. CLINICAL CORRELATION: DIABETES and FAT METABOLISM Metabolic changes in type 1 diabetes :The metabolic abnormalities of type 1 diabetes mellitus result from a deficiency of insulin which profoundly affects metabolism in three tissues: liver, muscle, and adipose tissue. 1. Hyperglycemia and ketoacidosis: Elevated levels of blood glucose and ketones are the hallmarks of untreated type 1 diabetes mellitus. Hyperglycemia is caused by increased hepatic production of glucose, combined with diminished peripheral utilization (muscle and adipose have the insulin-sensitive GLUT-4). Ketosis results from increased mobilization of fatty acids from adipose tissue, combined with accelerated hepatic fatty acid β-oxidation and synthesis of 3-hydroxybutyrate and aceto - acetate. [Note: Acetyl coenzyme A from β-oxidation is the substrate for ketogenesis and the allosteric effector of pyruvate carboxylase, a gluconeogenic enzyme.] Diabetic ketoacidosis (DKA, a type of metabolic acidosis) occurs in 25–40% of those newly diagnosed with type 1 diabetes, and may recur if the patient becomes ill (most commonly with an infection) or does not comply with therapy. DKA is treated by replacing fluid and electrolytes, and administering short-acting insulin to gradually correct hyperglycemia without precipitating hypoglycemia. 2. Hypertriacylglycerolemia: Not all the fatty acids flooding the liver can be disposed of through oxidation or ketone body synthesis. These excess fatty acids are converted to triacylglycerol, which is packaged and secreted in very- low-density lipoproteins. Chylomicrons are synthesized from dietary lipids by the intestinal mucosal cells following a meal. Because lipoprotein degradation catalyzed by lipoprotein lipase in the capillary beds of muscle and adipose This document is the property of PHINMA EDUCATION P a g e | 23  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule:_____________________________________ Date:________________ tissue is low in diabetics (synthesis of the enzyme is decreased when insulin levels are low), the plasma chylomicron and VLDL levels are elevated, resulting in hypertriacylglycerolemia. Figure 25.9: Intertissue relationships in type 1 diabetes. Lippincott, 7th ed Metabolic changes in type 2 diabetes: The metabolic abnormalities of type 2 diabetes mellitus are the result of insulin resistance expressed primarily in liver, muscle, and adipose tissue (Figure 25.10). 1. Hyperglycemia: Hyperglycemia is caused by increased hepatic production of glucose, combined with diminished peripheral use. Ketosis is usually minimal or absent in type 2 patients because the presence of insulin—even in the presence of insulin resistance—diminishes hepatic ketogenesis. [Note: Metformin, an oral agent for the treatment of type 2 diabetes, inhibits hepatic gluconeogenesis]. 2. Dyslipidemia: In the liver, fatty acids are converted to triacylglycerols, which are packaged and secreted in VLDL. Chylomicrons are synthesized from dietary lipids by the intestinal mucosal cells following a meal. Because lipoprotein degradation catalyzed by lipoprotein lipase in adipose tissue (and muscle) is low in diabetics, the plasma chylomicron This document is the property of PHINMA EDUCATION P a g e | 24  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule:_____________________________________ Date:________________ and VLDL levels are elevated, resulting in hypertriacylglycerolemia (see Figure 25.10). Low HDL levels are also associated with type 2 diabetes. Lippincott, 7th ed ). This document is the property of PHINMA EDUCATION P a g e | 25  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule:_____________________________________ Date:________________ Key concept map for diabetes. Lippincott, 7th ed This document is the property of PHINMA EDUCATION P a g e | 26  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule:_____________________________________ Date:________________ Activity 3: Skill building activities (25 mins + 5 minutes checking) MATCHING TYPE: DIGESTION: Match column A with column B. Write the letter before each number. COLUMN A COLUMN B A- Small intestine _____1.Interaction with bile occurs. B- Stomach _____2.Monoacylglycerols are produced. _____3.Chyme is produced. C- Intestinal cells _____4.Gastric lipases are active. D- Lymphatic system _____5.Micelles are repackaged MULTIPLE CHOICE: 1. Which of the following statements about digestion of 7. In triacylgycerol mobilization, triacylglycerol undergo dietary triacylglycerols in adults is correct? a. Hydrolysis a. It begins in the mouth b.Oxidation b. It occurs to a small extent (10%) in the stomach c.Phosphorylation c. It occurs only in the small intestine d.Isomerization d. No correct response. 8.Not a product of triacylglycerol mobilization 2. The semi-liquid material chyme is formed in the a.Fatty acids a. Mouth b.Glycerol b. Stomach c.ATP c. Small intestine d.No correct response d. Intestinal cells 9.The first stage of glycerol metabolism is a two-step 3. The major function of bile released during triacylglycerol process in which glycerol is converted to digestion to a.Pyruvate b. Facilitate the formation of chyme b.Glucose 6-phosphate c. Act as an enzyme c.Glycerol 3-phosphate d. Act as an emulsifier d.Dihydroxyacetone phosphate e. Transport fats 10.What is the intermediate compound in in two-step 4. The two major products of triacylglycerol digestion in the first stage of glycerol metabolism small intestine are fatty acids and a.Glycerol 2-phosphate a. Glycerol b.Glycerol 3-phosphate b. Monoacylglycerol c.Dihydroxyacetone phosphate c. Acetyl CoA d.No correct response d. Glucose 11. After the 1st stage of glycerol metabolism, the 5. Lipoproteins that transport TAG from intestinal cells to remaining stages is the same as the bloodstream a.Glucose pathway a. Chymes b.Glycogen pathway b. Chylomicrons c.Fatty acid pathway c. Fatty acid micelles d.Protein pathway d. Low density lipoprotein 12.In the oxidation of fatty acids, what two molecules 6. Hormone sensitive lipase needed for triacylglycerol are needed to initially activate a fatty acid molecule? mobilization is activated by a.Acetyl CoA and ATP a. cAMP b.CoA ad acyl CoA b. Epinephrine c.CoA and ATP c. adipocytes d.No correct reponse d. Adenyl cyclase This document is the property of PHINMA EDUCATION P a g e | 27  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule:_____________________________________ Date:________________ 13. In the oxidation of fatty acids, what molecule shuttles 19.Net ATP production during β-oxidation process is always activated fatty acid molecules across the inner 2 less than gross ATP production because ATP is consumed mitochondrial membrane? in fatty acid a.Citrate a.Activation b.Carnitine b.Transport c.CoA c.Both d.Acetyl CoA d.No correct response 14.The correct sequence for the four reactions of the β- 20. Not a ketone body oxidation pathway in terms of the “type of reaction a.Β-hydroxybutyrate occuring” is b.Acetoacetate a.Dehydrogenation, dehydrogenation, hydration, thiolysis c.Acetic acid b.Dehydrogenation, hydration, dehydrogenation, thiolysis d.Acetone c.Hydration, dehydrogenation, thiolysis, dehydrogenation 21.How many acetyl CoA molecules are used as reactants in d.Thiolysis, dehydrogenation, hydration, dehydrogenation the process of ketogenesis? 3.How many turns for β-oxidation pathway to process a a.1 C16 saturated fatty acids? b.2 a.7 c.3 b.8 d.4 c.16 22.The correct sequence for the four reactions of ketogenesis d.17 in terms of the “type of reaction occuring” is 15.How many turns for β-oxidation pathway to process a a.Condensation, condensation, hydrogenation, cleavage C16 unsaturated fatty acids? b.Condensation, cleavage, condensation, hydrogenation a.7 c.Condensation, condensation, cleavage, hydrogenation b.8 d.Condensation, hydrogenation, condensation, cleavage c.16 d.17 23.The characterization C4 + C2 C6 applies to which step 16.How many acetyl CoA molecules are produced when in the process of ketogenesis? C18 fatty acids is completely processed through β- a.Step 1 oxidation pathway? b.Step 2 a.8 c.Step 3 b.9 d.Step 4 c.18 24.How many units of acetyl CoA are produced when d.36 acetoacetyl CoA undergous cleavage using a thiolase? 17. How many FADH2 and NADH molecules are a.1 produced, respectively, during the one turn of the fatty b.2 acid β-oxidation pathway? c.3 a.1 and 1 d.4 b.1 and 2 25.The process of lipogenesis occurs in the c.2 and 1 a.Mitochondrial matrix d.2 and 2 b.Cell nucleus 18..Net ATP production during β-oxidation process is c.Cell cytosol always 2 less than gross ATP production because ATP is d.Ribosomes consumed in fatty acid a.Activation c.Both b.Transport d.No correct response This document is the property of PHINMA EDUCATION P a g e | 28  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: _____________________________________________________________ Class number: _______ Section: ____________ Schedule:_____________________________________ Date:________________ Activity 4: What I Know Chart, part 2 (2 mins) Instruction: To review what was learned from this session, please go back to Activity 1 and answer the “What I Learned” column. Notice and reflect on any changes in your answers. Activity 5: Check for understanding (15 mins) Instruction: Now it’s time for you to figure this one out on your own! Take time to read, analyze, and understand the following questions. For this instance, you will not have the chance to check if you have the correct answers since there are no more keys to correction. WRITE the letter of your choice before each number Good luck! 1. Which one of the following is elevated in plasma during 6. Which of these is able to cross the inner the absorptive (fed) period as compared with the mitochondrial membrane? postabsorptive (fasted) state? a. Acetyl–CoA a. Glucagon. b. Fatty acyl–carnitine b. Acetoacetate. c. Fatty acyl–CoA c. Chylomicrons. d. Malonyl–CoA 7. What is the correct order of function of the d. Free fatty acids.. following enzymes of β oxidation? 2. Relative or absolute lack of insulin in humans would result 1. β-Hydroxyacyl-CoA dehydrogenase in which one of the following reactions in the liver? 2. Thiolase a. Increased glycogenesis 3. Enoyl-CoA hydratase b. Decreased gluconeogenesis from lactate. 4. Acyl-CoA dehydrogenase c. Decreased glycogenolysis. a. 1,2,3,4 d. Increased formation of 3-hydroxybutyrate. b. 3,1,4,2 3. A young girl with a history of severe abdominal pain was c. 4,3,1,2 taken to her local hospital at 5 a.m. in severe distress. d. 1,4,3,2 Blood was drawn, and the plasma appeared milky, with the 8. If the 16-carbon saturated fatty acid palmitate is triacylglycerol level in excess of 2,000 mg/dl (normal = 4– oxidized completely to carbon dioxide and water (via the β-oxidation pathway and the citric acid cycle), and 150 mg/dl). The patient was placed on a diet severely all of the energy-conserving products are used to drive limited in fat, but supplemented with medium-chain fatty ATP synthesis in the mitochondrion, the net yield of acids. ATP per molecule of palmitate is: Which of the following lipoprotein particles are most likely a. 7. responsible for the appearance of the patient’ plasma? b. 8. a. Chylomicrons. c. 122. b. Very-low-density lipoproteins. d. 108. c. Low-density-lipoproteins. 9. Urine of a person contains abnormal quantities of d. High-density-lipoproteins. ________ during prolonged fasting 4. Name the most active organs in the animal body which a. amino acids have the ability to synthesize triacylglycerol? b. ketones c. glucose a. Spleen d. fats b. Kidney 10. Ketogenesis occurs primarily in ______ of liver c. Liver and intestines cells d. Adipose tissues a. Mitochondria 5. Triacylglycerol stored in the body as cytoplasmic lipid b. Cytosol droplets. Lipolysis is the hydrolysis of triacylglycerol. c. Endoplasmic reticulum a. Both statements are TRUE d. Golgi apparatus b. Both statements are FALSE c. Only the first statement is TRUE d. Only the first statement is FALSE This document is the property of PHINMA EDUCATION P a g e | 29  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: ____________________________________________________________ Class number: _______ Section: ____________ Schedule: ____________________________________ Date: _______________ Activity 6: Thinking about Learning (5 mins) A. Work Tracker: You are done with this session! Let’s track your progress. Shade the session number you just completed. P1 P2 1 2 3 4 5 6 7 8 9 10 B. Think about your Learning: Tell me about your thoughts! Today’s topic is all about the Lipid Metabolism. 1. What interests you about the lesson today? 2. Do you have questions in mind that you are interested to be discussed? Please write it down. ___________________________________________________________ ___________________________________________________________ ___________________________________________________________ ________________________________________________________ ___________________________________________________________ __________________________________________________________ KEY TO CORRECTION: ACTIVITY 3: MATCHING MCQ MCQ MCQ MCQ MCQ TYPE: 1.B 6.A 11.A 16.A 21.C 1.A 2.B 7.A 12.C 17.A 22.C 2.A 3.C 8.C 13.B 18.A 23.B 3.B 4.A 9.D 14.B 19.A 24.B 4.B 5.B 10.B 15.A 20.C 25.A 5.C This document is the property of PHINMA EDUCATION P a g e | 30  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: ____________________________________________________________ Class number: _______ Section: ____________ Schedule: ____________________________________ Date: _______________ RATIONALE: ACTIVITY 3 MCQ 1. B:Adult dieatry triacylglycerol digestion occurs to a small extent (10%) in the stomach. The saliva of infants contains a lipase that can hydrolyze TAGs, so digestion begins in the mouth for nursing infants. Because mother’s milk is already a lipid-in-water emulsion, emulsifications by stomach churning is a much less important factor in an infant’s processing of fat. Mother’s milk also contains a lipase that supplements the action of the salivary lipases the infant itself produces. After weaning, infants cease to produce salivary lipases.Carbohydrates digestion are the ones that begins in the mouth. Protein digestion occurs in the small intestine. Triacylglycerol mobilization is the hydrolysis of triacylglycerols stored in adipose tissue, followed by release into the bloodstream of the fatty acids and glycerol so produced. Triacylglycerol mobilization is an ongoing process. On the average, about 10% of the TAGs in adipose tissue are replaced daily by new triacylglycerol molecules. 2. B: Stomach is where semi-liquid material chyme is formed. 3. C: Act as an emulsifier is major function of bile released during triacylglycerol digestion. Bile is the greenish-yellow fluid (consisting of waste products, cholesterol, and bile salts) that is secreted by the liver cells to perform 2 primary functions: To carry away waste. To break down fats during digestion. 4. A: Glycerol: The two major products of triacylglycerol digestion in the small intestine are fatty acids and Glycerol 5. B: Chylomicrons: Chylomicrons transport lipids absorbed from the intestine to adipose, cardiac, and skeletal muscle tissue, where their triglyceride components are hydrolyzed by the activity of the lipoprotein lipase, allowing the released free fatty acids to be absorbed by the tissues. 6. A: Hormone sensitive lipase needed for triacylglycerol mobilization is activated by cAMP. Adipose cells are among the largest cells in the body. They differ from other cells in that most of the cytoplasm has been replaced with a large triacylglycerol droplet (Figure 25.4). This droplet accounts for nearly the entire volume of the cell. As newly formed TAGs are imported into an adipose cell, they form small droplets at the periphery of the cell that later merge with the large central droplet. Use of the TAGs stored in adipose tissue for energy production is triggered by several hormones, including epinephrine and glucagon. Hormonal interaction with adipose cell membrane receptors stimulates production of cAMP from ATP inside the adipose cell. In a series of enzymatic reactions, the cAMP activates hormone-sensitive lipase (HSL) through phosphorylation. HSL is the lipase needed for triacylglycerol hydrolysis, a prerequisite for fatty acids to enter the bloodstream from an adipose cell. This cAMP activation process is illustrated in Figure 25.5. This document is the property of PHINMA EDUCATION P a g e | 31  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: ____________________________________________________________ Class number: _______ Section: ____________ Schedule: ____________________________________ Date: _______________ 7. A: Hydrolysis: triacylglycerol undergoes hydrolysis in TAG mobilization. Triacylglycerol (TAG) stored in adipose tissue can be rapidly mobilized by the hydrolytic action of lipases, with the release of fatty acids (FA) that are used by other tissues during times of energy deprivation. Unlike synthesis of TAG, which occurs not only in adipose tissue but also in other tissues such as liver for very-low-density lipoprotein formation, hydrolysis of TAG, lipolysis, predominantly occurs in adipose tissue. Until recently, hormone-sensitive lipase was considered to be the key rate-limiting enzyme responsible for regulating TAG mobilization. 8. C: ATP. The two major products of triacylglycerol digestion in the small intestine are fatty acids and Glycerol. 9. D: The first stage of glycerol metabolism is a two-step process in which glycerol is converted to Dihydroxyacetone phosphate: 10. B: Glycerol 2-phosphate. Refer to no. 9. 11. A: Glucose pathway 12. C: CoA and ATP: 1st step of fatty acid oxidation 13. B: Carnitine: shuttles activated fatty acid molecules across the inner mitochondrial membrane during fatty acid oxidation. The carnitine shuttle, a transport chain that consists of three enzymatic reactions, helps fatty acids to pass the mitochondrial membrane. Carnitine acyltransferases (CrATs, COTs, CPTs) are part of the carnitine shuttle. The first step of the carnitine shuttle is the activation of fatty acids. This document is the property of PHINMA EDUCATION P a g e | 32  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: ____________________________________________________________ Class number: _______ Section: ____________ Schedule: ____________________________________ Date: _______________ 14. B: Dehydrogenation, hydration, dehydrogenation, thiolysis 15. A: 7: The fatty acids normally found in dietary triacylglycerols contain an even number of carbon atoms. Thus, the number of acetyl CoA molecules produced in the β-oxidation pathway is equal to half the number of carbon atoms in the fatty acid. The number of repetitions of the b-oxidation pathway that are needed to produce the acetyl CoA is always one less than the number of acetyl CoA molecules produced because the last repetition produces two acetyl CoA molecules as a C4 unit splits into two C2 units. But for unsaturated fatty acids their oxidation through the β-oxidation pathway requires two additional enzymes besides those needed for oxidation of saturated fatty acids. These two—an epimerase that can change a D configuration to an L configuration and a cis–trans isomerase—are needed for two reasons. 16. A: 8 please refer to question number 15. 17. A: 1 and 1 18. A: Net ATP production during β-oxidation process is always 2 less than gross ATP production because ATP is consumed in fatty acid Activation 19. A: Net ATP production during β-oxidation process is always 2 less than gross ATP production because ATP is consumed in fatty acid Activation 20. C: Acetic acid is not a ketone body. Ketone bodies are: Β-hydroxybutyrate, Acetoacetate, Acetone 21. C: 3 This document is the property of PHINMA EDUCATION P a g e | 33  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: ____________________________________________________________ Class number: _______ Section: ____________ Schedule: ____________________________________ Date: _______________ For number 21 22. C: Ketogenesis is the biochemical process through which organisms produce ketone bodies by breaking down fatty acids and ketogenic amino acids. Condensation, condensation, cleavage, hydrogenation 23. B: Step 2 24. B. 2 25. A: Mitochondial matrix. Although lipogenesis occurs in the cytoplasm, the necessary acetyl CoA is created in the mitochondria and cannot be transported across the mitochondrial membrane. This document is the property of PHINMA EDUCATION P a g e | 34  Course Code: BIO 024 (Biochemistry/Biomolecules) Student Activity Sheet Module #9 Name: ____________________________________________________________ Class number: _______ Section: ____________ Schedule: ____________________________________ Date: _______________ SUGGESTED VIDEOS: Lipid digestion and absorption: https://www.youtube.com/watch?v=80Edf1o_vDM Lipid digestion and absorption on the 7th minutes to 9:15th minutes: https://www.youtube.com/watch?v=BVxeeiR7JB0 Lipid metabolism general overview: https://www.youtube.com/watch?v=ppqpUVaasNc Beta-oxidation Part 1: https://www.youtube.com/watch?v=__jS-pjzb5k Beta-oxidation Part 2: https://www.youtube.com/watch?v=ZufZvbhPpws Ketone bodies and ketogenesis: https://www.youtube.com/watch?v=AK9Q2ClI8y4 Lipogenesis: https://www.youtube.com/watch?v=s_sFNG_coSs This document is the property of PHINMA EDUCATION P a g e | 35