MT Clinical Chemistry 1 Lecture Notes PDF

MT CLINICAL CHEMISTRY 1 6317 LECTURE SHIFT 1 F CARBOHYDRATES UNIT 3: CARBOHYDRATE...

MT CLINICAL CHEMISTRY 1 6317 LECTURE SHIFT 1 F CARBOHYDRATES UNIT 3: CARBOHYDRATES GENERAL DESCRIPTION AND ITS METABOLISMS Compounds containing C, H and O Sources: All of them contain Book: Bishop’s Clinical Chemistry : Principles, Techniques, ○ C=O and -OH functional groups Correlations (8th Edition) Are hydrates of aldehyde or ketone derivatives Ppt: Carbohydrates and its Metabolism Prof Name’s Discussion: Dr. Vincent Thomas Alferos, Dr. John ETYMOLOGY AND STRUCTURE OF CARBOHYDRATES Henrick Uy, Ma’am Vivian Asuncion OUTLINE CARBOHYDRATES 1 Classification Of Carbohydrates 2 Monosaccharides, Disaccharides, And Polysaccharides 3 Chemical Properties Of Carbohydrates 4 Fate Of Glucose 4 Carbohydrate Digestion 4 Glucose Metabolism 6 Substances containing carbon, hydrogen, and oxygen Pathways Of Glucose Metabolism 6 Usually has one water molecule per carbon CARBOHYDRATE METABOLISM REGULATION 13 Carbohydrates are actually hydrated carbons HYPERGLYCEMIA 18 Most common carbohydrate in our body would be the Laboratory Findings In Hyperglycemia 18 DIABETES MELLITUS (DM) 19 hexoses (6-Carbon molecules) Criteria For Testing For Prediabetes And Diabetes 19 The image above shows an aldohexose wherein there is an Criteria For The Diagnosis Of Diabetes Mellitus 20 aldehyde group attached to one end making it D-glucose Criteria For Testing And Diagnosis Of Gdm 21 Similarities And Differences Of Dm1 And Dm2 21 CLASSIFICATION OF CARBOHYDRATES Classification Of Dm 21 Size of the carbon chain Type 1 Diabetes 22 Location of the CO functional group Methods Of Detecting Type 1 Diabetes Mellitus Autoantibodies 23 ○ Is it in between two carbons or on the terminal side? Type 2 Diabetes 23 Number of sugar units Other Types Of Diabetes 24 ○ The simplest being the monosaccharides Impaired Fasting Glucose And Impaired Glucose Tolerance 24 Stereochemistry of the compound Gestational Diabetes Mellitus (Gdm) 25 ○ Isomers Testing For Gdm 25 Screening And Diagnosis Of Gdm 25 Pathophysiology Of Diabetes Mellitus 26 SIZE OF CARBON CHAIN When To Test For Dm? 27 Trioses (3-Carbon Chain) When To Test For Type 2 Dm? 27 ○ Usually would be the intermediary in the metabolism Maturity-Onset Diabetes Of The Young (Mody) 27 ○ Simplest form of carbohydrates HYPOGLYCEMIA 28 ○ Ex: Glyceraldehyde Classification Of Hypoglycemia 29 Tetroses (4-Carbon Chain) Genetic Defects In Carbohydrate Metabolism 29 Glycogen Storage Diseases 31 Pentoses (5-Carbon Chain) Glycogenolysis 32 ○ Seen in our nucleic acids OTHER CAUSES OF HYPOGLYCEMIA 32 ○ Examples: LABORATORY TESTING FOR CARBOHYDRATES 32 Ribose Methods Of Glucose Measurement 33 Xylose Self-Monitoring Of Blood Glucose 34 Hexoses (6-Carbon Chain) Diagnostic Tests For Dm 34 ○ Most of what we have in the body would be the hexoses Fasting Blood Sugar 34 Methods Of Diagnosis 38 ○ Examples: Methods Of Glucose Determination 38 Fructose Enzymatic Methods 38 Glucose Other Useful Compounds For Dm Diagnosis: Ketones 40 Galactose Other Useful Compounds For Dm Diagnosis: Islet Autoantibody 41 Other Useful Compounds For Dm Diagnosis: Insulin 41 Insulin Detection 41 QUESTIONS 42 _____________________________________________________ 1  UNIT 3: CARBOHYDRATES AND ITS METABOLISMS LOCATION OF THE CO FUNCTIONAL GROUP Aldose (aldehyde) ○ Terminal carbon group (O=CH-) ○ Aldehyde group ○ Example: Glucose Ketose (ketone) ○ Carbonyl group in the middle linked to carbon atoms (C=O) ○ Ketone group ○ Example: Fructose The Fischer projection shows the aldehyde/ketone at the top of the drawing The Haworth projection represents the compound in a cyclic form ○ Formed when the functional group reacts with an alcohol group of the same sugar to form a hemiketal or hemiacetal ring NUMBER OF SUGAR UNITS Difference of starch and glycogen: Monosaccharides ○ Both would be composed of the same unit of ○ Fructose carbohydrates monosaccharides: glucose ○ Galactose ○ The bonds they are forming. Disaccharides Although the connecting bond in starch is alpha, ○ Lactose - glucose + galactose linked by β-1,4 the one that digests it is the alpha-amylase. glycosidic bond Starch and cellulose is quite similar: ○ Sucrose ○ Starch ○ Maltose - made of 2 glucose units and are linked by a Presence of alpha-glycosidic bond glycosidic bond ○ Cellulose Oligosaccharides - 2-10 monosaccharide units Presence and component of dietary fibers Polysaccharides - above 10 units Humans are unable to digest some plants ○ Starch because because we don’t have the cellulase ○ Glycogen - storage form of glucose in the body Usually found in our plants which are not exactly Linear: connected by an alpha 1,4 bond digestible Branch: connected by an alpha 1,6 bond They are still dietary requirements because they form the bulk of the stool. BASED ON NUMBER OF SUGAR UNITS Stereochemistry of the compound ○ Allows for different various spatial arrangements around each asymmetric carbon (stereoisomers) Enantiomers on the other hand, are non-superimposable ○ D or L type Assigned according to the configuration of the highest numbered asymmetric carbon called configurational atom or chiral center Beta-Lactose Most sugars in humans are in D-type In the penultimate carbon, the You can find the hydroxyl group on the fifth carbon on the alpha and beta configuration right side; while in L isomers, this can be found on the left will be determined by hydroxyl side. whether pointing upwards or downwards 2  UNIT 3: CARBOHYDRATES AND ITS METABOLISMS BASED ON STEREOCHEMISTRY MONOSACCHARIDES, DISACCHARIDES, AND POLYSACCHARIDES This chaining of sugars relies on the formation of glycosidic bonds that are bridges of oxygen atoms. When carbohydrate molecules join, a water molecule is produced. When they split, one molecule of water is used to form the individual compounds. This reaction is called hydrolysis. MONOSACCHARIDES Simple sugars that cannot be hydrolyzed to a simpler form. Can contain three, four, five, and six or more carbon atoms. Glucose, fructose, and galactose are the most common examples. Stereoisomers - they have asymmetric carbons ○ Purpose of asymmetric carbons is to allow for different DISACCHARIDES spatial arrangements Formed when two monosaccharide units are joined by a Chiral carbons - carbons with four different groups glycosidic linkage. attached to it During hydrolysis, disaccharides will be split into two General formula for each asymmetric carbon: 2n monosaccharides by disaccharide enzymes (e.g., lactase). possible isomers where n is the number of chiral carbons Maltose, lactose, and sucrose are the most common ○ Example 1: Glyceraldehyde with only 1 chiral carbon examples. would have 21 = 2 possible isomers - D and L-glyceraldehyde OLIGOSACCHARIDES ○ Example 2: For D-glucose, there are 4 chiral carbons so 24 = 16 possible isomer Enantiomers - mirror images of each other D and L-glucose would be mirror images of one another The determinant is found on the penultimate carbon ○ It is the asymmetric carbon farthest from the carbonyl group The chaining of 2 to 10 sugar units, whereas ○ If -OH group is on the right side - D-glucose polysaccharides are formed by the linkage of many ○ If -OH group is on the left side - L-glucose monosaccharide units. Majority of the glucose in our body is in the D-form because During hydrolysis, polysaccharides will yield more than 10 L-forms cannot be acted upon by hexokinase which is an monosaccharides. enzyme used in the glycolytic pathway. Starch and glycogen are the most common examples. L-forms are then converted to D-forms to be utilized by the body D-Glucose CHEMICAL PROPERTIES OF CARBOHYDRATES ○ In linear form Some carbohydrates are reducing substances; to be a ○ Dextrorotatory reducing substance, the carbohydrate must contain a ketone Hydroxyl (-OH) is on the right side or aldehyde group. Called “dextrose” during the old days Examples of reducing substances include: glucose, maltose, This glucose is most abundant in our body that fructose, lactose, and galactose. can be utilized. Carbohydrates can form glycosidic bonds with other L-glucose carbohydrates and with noncarbohydrates. ○ Levorotatory Non-reducing carbohydrates do not have an active ketone or Hydroxyl (-OH) is on the left side aldehyde group; they will not reduce other compounds. o This glucose still needs to be isomerized to its The most common non-reducing sugar is sucrose—table dextrorotatory form. sugar. 3  UNIT 3: CARBOHYDRATES AND ITS METABOLISMS HAWORTH PROJECTION OF SUCROSE SMALL INTESTINE Source of disaccharidases that still need to be digested on the brush border of the small intestine because it is where disaccharidases are formed Example of disaccharides: ○ Fructose + glucose = sucrose ○ Glucose + galactose = lactose (milk and dairy products) ○ Glucose + glucose = maltose FATE OF GLUCOSE During acute diarrhea (infectious or non-infectious) and the Salivary amylase and pancreatic amylase are responsible small intestine is scratched, we are advised not to take milk for the digestion of nonabsorbent polymers to dextrins and products because we would acquire lactose intolerance. We disaccharides. are unable to digest lactose because of the lactase which is When disaccharides are converted to monosaccharides, they eroded. We give medications to grow back the small intestine are absorbed by the gut and transported to the liver by the lining. hepatic portal venous blood supply. Remember: Humans can absorb monosaccharides (glucose, Glucose metabolization is catalyzed by the enzyme galactose, fructose). hexokinase. Glucose-6-phosphate can enter the Peristalsis continue even to duodenum (entry to small Embden-Meyerhof pathway or the hexose monophosphate intestine) pathway (HMP) or can be converted to glycogen. When the food ends up here (aka chyme) the pancreas will secrete several enzymes, including pancreatic amylase CARBOHYDRATE DIGESTION Disaccharide will be broken down to monosaccharides More ingested CHO are polymers ○ Starch (Ex: rice, bread) LIVER ○ Glycogen (Ex: meat which is also a rich source of carbohydrates) GLUCOSE Only CHO that can be directly used for energy or storage MOUTH ○ Final product Chewing (mastication) ○ A process of breaking down food into smaller MODES OF DIGESTION components ○ Mechanical digestion: some starch will be broken down Mechanical: chewing; muscular action that break down food to dextrin and some into disaccharidases mass to smaller portions Salivary glands secrete amylase, which digest starch Chemical: enzymes reaction that breaks down food nutrients chemically into simpler compounds/form Convert polysaccharides to dextrin and disaccharides ○ Enzymes needed: Amylase + Starch -> Dextrin + disaccharide Maltase: released by the intestinal mucosa Sucrase: hydrolyze sucrose to glucose and fructose Lactose is hydrolyzed to glucose and galactose STOMACH Monosaccharides are absorbed by the gut and transported Peristalsis: muscular wave-like, pushes down the food into to the liver by the hepatic portal the stomach; provides mechanical digestion ○ Other monosaccharides like galactose and fructose must The acid condition halts the action of amylase be converted first to glucose 20-30% starch are converted to disaccharide & dextrin After glucose enters the cells it is shunted into one of the 3 The macromolecules nutrient that is chemically digested in metabolic pathways, before it will be converted to energy, the mouth via oral digestion. Subsequently, it will be releasing CO2 and water denatured in the stomach. glucose is dependent on the availability of substrates and In the stomach, your pancreatic amylases will take place nutritional status of the cell and peristaltic movement will continue up to the small Ultimate goal of the cell is to convert glucose into CO2 and intestine. glucon ○ Pancreatic amylases: ultimately breaks food down into Once the sugars enter, the glucose can be converted into disaccharidases and dextrin glucose and stored as liver glycogen Human body is not capable of producing starch (only plants INTESTINES and other photosynthetic organisms can) Pancreatic amylases will try to convert your disaccharides into monosaccharides 4  UNIT 3: CARBOHYDRATES AND ITS METABOLISMS CARBOHYDRATE DIGESTION GLUCOSE METABOLISM Nervous tissue cannot concentrate or store carbohydrates; therefore, it is critical to maintain a steady supply of glucose to the tissue. The concentration of glucose in the ECF (extracellular fluid) must be maintained. When the concentration falls below a certain level, the nervous tissue is incapable of maintaining normal function. PATHWAYS OF GLUCOSE METABOLISM Embden Meyerhof Pathway (tricarboxylic acid cycle) ○ Glucose is broken down into two three-carbon molecules of pyruvic acid ○ Other substrates: Glycerol Fatty acids Ketones ○ ATP: Used = 2 Produced = 4 NET gain = 2 Hexose Monophosphate Shunt ○ Detour of glucose-6-phosphate from the glycolytic pathway to become 6-phosphogluconate Glycogenesis Digestion starts in the mouth since salivary amylase is ○ Only when the body’s energy requirements are being met present If the suffix is -genesis, it means “formation.” While a person is chewing rice and breaking it down into The glucose will be converted to glycogen smaller components, the salivary gland is stimulated to Remember that the reverse process (glycogenolysis) release salivary amylase of this occurs in the liver and is also accomplished in Rice contains starch which is a polysaccharide. the same tissues (liver, muscles, and other cells). Amylase will act upon starch producing dextrin and ○ Only in the liver disaccharide. The chain of starch is reduced into dextrin and WHEN GLUCOSE IS LOW... disaccharide The food bolus passes through the esophagus Then it reaches the stomach through peristalsis The mechanical digestion through peristalsis triggers the release of hydrochloric acid ○ This triggers the inactivation of the salivary amylase (the amylase is slightly alkaline) Both pathways are used to provide glucose in the body. ○ 20-30% of the starch is converted to disaccharides When do we use each pathway and dextrin At what condition? Eventually it will reach the small intestine, where the majority of absorption in the duodenum occurs Glycogenolysis Pancreas will then release enzymes, pancreatic Breaking down the stored glycogen amylase and bicarbonate to counteract the hydrochloric Gluconeogenesis acid during the chemical digestion in the stomach Outsourcing glucose from non-carbohydrate sources ○ This provides an environment for the pancreatic like protein and lipids amylase (alkaline in nature) to work During the first 24 hours of fasting the body uses glycogen The amylase further breaks down the disaccharides and as the source of glucose production. dextrins If fasting is done for more than 24 hours, there is a Eventually reaching the brush border of the intestine, possibility that your body’s glycogen content can be contains the villi and the surface area that aids digestion, depleted; your body then resorts to other forms of and the disaccharidases (ex. Lactase, maltase) generating glucose from other resources in the body such After the process, monosaccharides will remain to be as fatty acids, glycerol, and ketone bodies. used as energy 5  UNIT 3: CARBOHYDRATES AND ITS METABOLISMS We can last up to how many days without eating, but we still For each of the molecules to enter the glycolytic cycle (fatty have at least energy to move. During the fast, the glucose acids, amino acids, galactose etc), phosphorylation may is supplied in the extracellular fluid of the liver (which occur which needs ATP has glycogen). There is lysis of glycogen that can be 2 ATP serves as an investment for the cycle, one to convert converted to glucose to provide the body with energy. glucose to glucose-6-phosphate and also one to produce When the fasting period is longer than 1 day, glucose is fructose 1,6-diphosphate. synthesized from other sources such as stored fats (our The net production via glycolysis is 2ATP stored fats get converted to release energy, there is also a In the case of excess glucose, it will be stored via tendency that ketone bodies will be produced in this process glycogenesis (glycogen synthase - rate limiting step) because the body will use up the stored fats which will lead Glucose is broken down into two three-carbon molecules to a formation of ketones). This is the concept of Keto diet. of pyruvic acid ○ You avoid eating Carbs and try to only eat fats Other substrates that can enter the pathway are ○ Due to the absence of carbs, the body will then use fats ○ Glycerol (from triglycerides) to produce glucose ○ Fatty acids (from triglycerides) ○ However, this can cause a complication called ○ Ketones (from glycolysis) Ketoacidosis. A higher concentration of ketones are It ends with the production of pyruvate, which is converted produced because of the high amount of fats taken in to Acetyl-CoA ○ Ketones are blood acids Acetyl-CoA will enter the Tricarboxylic Acid Cycle ○ Tricarboxylic Acid Cycle: is the final step where the EMBDEN MEYERHOF PATHWAY body produces energy ○ Ways where you can get Acetyl-CoA: Lipids -> Fatty Acids Protein -> Amino Acids Ketones The up and down arrows signify that the process is reversible When glucose levels are high, your body produces insulin, and will cause the glucose to enter the cell Organs that are insulin dependent include the liver, skeletal muscle, and fat The action of Hexokinase traps the glucose inside the cell, using ATP, and converts the glucose to glucose-6-phosphate through phosphorylation It is converted to fructose-6-phosphate and phosphorylated again to form fructose-1,6-diphosphate with the aid of the enzyme, phosphofructokinase ○ The enzyme is a turning point and determines whether glycolysis will be inhibited or not Then the fructose-1,6-diphosphate is split to form 2 molecules of glyceraldehyde-3-phosphate It is then converted to 3-Phosphoglycerol phosphate and generates 2 NADH and 2 ATP and then 3-phosphoglycerate is formed To fuel metabolism, ATP from the glucose is harvested It 3-phosphoglycerate is converted to via the embden meyerhof pathway and alternatively the phosphoenolpyruvate and then the phosphate group will hexose monophosphate shunt or the pentose phosphate be removed with the aid of pyruvate kinase to form pathway pyruvate, generating 2 ATP Glucose will undergo glycolysis to produce pyruvate If oxygen is present, the pyruvate will enter the tricarboxylic which can transition to form ATP, but with the absence of acid cycle and converts to Acetyl-CoA with the aid of oxygen, lactase will be produced causing lactic acidosis. Lactate dehydrogenase It is also through the pyruvate that amino acids enter However, if oxygen is absent, the environment is bioenergetics (but they are reserved) Anaerobic. Thus, your pyruvate will be converted into your Lipids enter the glycolytic pathway through glycerol being lactate. converted to 3-phosphoglycerol If you could notice in the figure, it has arrows moving Fatty acids from the triacylglyceride which is also forward and backward. Meaning, there is a reverse in the energy-forming can enter through Acetyl-CoA glycolytic pathway, which is your gluconeogenesis (Conversion of Pyruvate/ Acetyl-CoA to Glucose). 6  UNIT 3: CARBOHYDRATES AND ITS METABOLISMS If you’ve noticed, those on the side pathways, the one on HEXOSE MONOPHOSPHATE SHUNT the right of Glucose 6-P04 is your hexose monophosphate shunt which is used to generate your pentoses. And aside from generating your pentoses such as your ribose which can be used to synthesize your nucleic acids. Or these pentoses can enter the glycolytic pathway through Fructose 6-PO4. What if you’re in a high-energy state? Your Glucose 6-PO4 would be converted to your Glucose 1-PO4 and would be acted upon by your glycogen synthase to form your glycogen. Detour of glucose-6-phosphate from the glycolytic Remember which state of the body will stimulate the pathway to become 6-phosphogluconic acid through formation or breakdown of glycogen oxidation. This permits the formation of Lipids/ Triglycerides is “tri,” so it has three (3) fatty acids + ribose-5-phosphate and NADP in its reduced form glycerol/glyceride. (NADPH). The glycerol can enter the glycolytic pathway through the NADPH is important to erythrocytes that lack mitochondria 3-Phosphoglycerate. When the need arises, we could (incapable of the TCA cycle). The reducing power of create glucose from non-glucose sources (known as NADPH is for the protection of the cell from oxidative and gluconeogenesis) free radical damage. Without NADPH, the lipid bilayer The Fatty Acids can enter the Acetyl-CoA. If it lacks energy, membrane of the cell and critical enzymes will be it will enter the Krebs Cycle. If it lacks glucose, it will enter destroyed, resulting in cell death. gluconeogenesis to generate glucose. HMP shunt permits pentoses, such as ribose, to enter the The Proteins/ Amino acids can enter through pyruvate glycolytic pathway. (glucogenic amino acids), acetyl CoA (through ketogenic Some of the 6-phosphogluconate are converted to ribose amino acids), or they can be transaminated for forming and some enter to the glutathione reductases which are your α-keto acids (through the Krebs cycle) metabolic function in the kidney There are a lot of side pathways. If our body lacks a Glucose will act upon Hexokinase to produce substrate, it can derive another substrate to form glucose. Glucose-6-phosphate which in the presence of Basically, it has plans A, B, C to generate your energy. Glucose-6-phosphate dehydrogenase and at the same What should we master in this diagram? Know what time there is a production of your NADP+ and NADPH, metabolic pathway would be stimulated given if you’re in a there is a production of 6-phosphogluconate. high/low energy state or what metabolic pathway would be This 6-phosphogluconate is important in several active if you’re in a starvation phase,etc. biosynthetic reactions. This pathway requires oxygen and is called the aerobic Example of biosynthetic reaction: pathway. ○ It may end up in the production of ribose (which is Glycerol released from the hydrolysis of triglycerides can important in the nucleic acid production.) enter at 3-phosphoglycerate. ○ Also, in the conversion of the NADP+ to NADPH. Fatty acids and ketones and some amino acids are NADPH is important to convert your glutathione and converted/catabolized to acetyl-CoA as part of the TCA reduce it because reduced glutathione has a very cycle. potent antioxidant activity. Other amino acids enter as pyruvate or as deaminated ○ Glutathione is very important to prevent the oxidation α-oxoacids. of hemoglobin. Because if hemoglobin becomes Gluconeogenesis is the conversion of amino acids by the oxidized, they are no longer capable of combining with liver and other specialized tissue (i.e. kidney) into oxygen. substrates that can be converted to glucose. It G6PD is used for the conversion of glucose-6-phosphate to encompasses the conversion of glycerol, lactate, and 6-phosphogluconate. pyruvate to glucose. Hexose Monophosphate Shunt (HMS) is also called your Anaerobic glycolysis is important to tissues (i.e. muscle) Pentose phosphate that have important energy requirements without an Pentose product of HMS: Ribose adequate oxygen supply. These tissues can derive ATP ○ Ribose is a pentose from glucose by converting pyruvic acid into lactic acid. ○ Ribose pentose pathway The lactic acid diffuses from the muscle cells to enter the ○ Ribose can enter the glycolytic pathway through your systemic circulation and is then taken up and used by the Fructose 6-PO4, or it can be used to synthesize your liver. nucleic acids ○ Sugar of your nucleic acids The first enzyme for your hexose monophosphate shunt or pentose phosphate pathway is your 7  UNIT 3: CARBOHYDRATES AND ITS METABOLISMS glucose-6-phosphate dehydrogenase (G6PD) that PENTOSE PHOSPHATE PATHWAY (SHUNT) converts your glucose-6-phosphate to your (YOUTUBE VIDEO) 6-phosphogluconate Also known as the Hexose Monophosphate shunt So, in this step, we won’t focus on G6PD. But instead, we Occurs in virtually all cell types and tissues will focus on the reducing equivalents that we get from the ○ Liver - 30% glucose metabolized by PPP. The liver G6PD reaction. also uses this pathway to protect itself from oxidative NADP+ (Oxidized Form) can generate a reduced form of stress due to drug metabolism your NADP ○ RBCs - use this to maintain oxidative capacity What’s the importance of NADP? The presence of your ○ Muscles don’t use this pathway often reduced NADPH is a protective mechanism, especially in Occurs in the cytoplasm the red blood cells. Produces NADPH ○ Red blood cells don't have organelles, or its organelles ○ NADPH is necessary for several pathways are absent, specifically, its mitochondria. Thus, it Fatty acid synthesis (50% of NADPH usually goes cannot undergo Krebs Cycle. Meaning, the RBC does to this) not have any protection against oxidative damage. Oxidative stress homeostasis ○ When your RBC is exposed to the oxidants, your Cytochrome P450 enzymes reduced glutathione will serve as a sacrifice that Produces trioses, hexoses, and pentoses prevents the oxidant from damaging the red blood ○ Pentoses are necessary for nucleotide synthesis cells. Pathway: ○ With the presence of your NADPH, you can generate reduced glutathione (2G-SH). If it’s oxidized, it will turn into GS-SG. GS-SG would now be worthless since it no longer has antioxidant properties. The only way to regain its antioxidant property is through the Glutathione reductase, which makes use of your NADPH. Redox reaction: If a substance is reduced, there must also be a substance to be oxidized in exchange. In this case, NADPH is to be oxidized to gain your reduced glutathione which has ○ Begins with Glucose-6-Phosphate (G6P) being antioxidant activity. shunted from the glycolysis pathway by the enzyme If there is an absence of G6PD, you won’t be able to Glucose-6-Phosphate Dehydrogenase (G6PD) generate the reducing equivalence (NADPH). Once the ○ G6PD converts G6P into reduced glutathione is oxidized, it won’t be able to generate Glucono-1,5-lactone-6-Phosphate the antioxidant activity of the reduced glutathione since the NADP+ is reduced to NADPH during this process NADPH is already absent. With that, there is no protector This is the rate limiting step for this pathway in the cell’s antioxidant activity of your reduced glutathione. Low levels of NADPH can activate G6PD, but high levels With that, your cells will be destroyed of it can inhibit the enzyme ○ G6PD is a newborn screening test to be screened ○ Glucono-1,5-lactone-6-Phosphate can be converted for inborn error of metabolism. into 6-Phosphogluconate, and then into ○ Those patients with G6PD deficiency are not allowed Ribulose-5-Phosphate to be exposed to aerosols, Lysol, oxidative drugs The conversion of 6-Phosphogluconate into (antimalarial drugs), flavabins, mothballs since these Ribulose-5-Phosphate is done by the enzyme can cause oxidant damage. 6-Phosphogluconate Dehydrogenase ○ There would be destruction of RBC to the exposed During this conversion, another NADP+ is converted into individuals that are lacking G6PD resulting in NADPH hemolytic anemia in their G6PD deficiency. From Ribulose-5-Phosphate, it can be converted to Xylulose-5-Phosphate (first bullet) or Ribose-5-Phosphate (second bullet). ○ Ribulose-5-Phosphate is then converted to Xylulose-5-Phosphate by the enzyme Ribulose-phosphate 3-epimerase This can be further converted into Fructose-6-Phosphate which can go back to the 8  UNIT 3: CARBOHYDRATES AND ITS METABOLISMS glycolysis pathway to be used for the generation Once the cell has a reduced glutathione, it can take the of ATP glutathione and utilize it by the enzyme glutathione NOTE: It’s clever how the cells can do this, if it peroxidase needs NADPH, it can just redirect to pentose ○ By doing so, it can reduce and process the hydrogen phosphate pathway then back to glycolysis peroxide into 2 H2O, so it can actually process pathway to get ATP as well something that's potentially dangerous and toxic to the ○ Ribulose-5-Phosphate is then converted to cell into something that's not Ribose-5-Phosphate by the enzyme Ribose ○ we can convert hydrogen peroxide into two water phosphate isomerase molecules is can be further converted into Mechanism by which a cell reduces its oxidative 5-phosphoribosyl-1-pyrophosphate (PRPP) stress; very important particularly in erythrocytes (molecule that determines pyrimidine or purine or red blood cells synthesis) which can be directed to erythrocytes depend critically on the pentose 5-phosphoribosyl-1-pyrophosphate (PRPP) can phosphate pathway for NADPH generation and be directed into Pyrimidine Synthesis or Purine oxidative stress capacity Synthesis This pathway is critical for erythrocytes In cells that have nucleotides, it can be broken One of the major malfunctions of this pathway occurs in the down into Ribose-5-Phosphate can be redirected first step or first enzyme: to glycolysis pathway, either for ATP generation or Glucose 6-Phosphate Dehydrogenase Glucose generation ○ Deficiency of glucose 6-phosphate dehydrogenase can ○ NOTE: A lot of these are reversible (not necessarily occur one-directional). Recall: glucose 6-phosphate dehydrogenase is The pathway can proceed in multiple directions the first rate limiting step of the pentose depending on what the cell needs. If it needs ATP, phosphate pathway it can go to the glycolysis pathway; if it’s going to 7.5% of world population deficient (one of the create nucleotides for nucleotide synthesis, it can most prevalent genetic disorders in the world) go to PRPP synthesis. 35% prevalence in certain areas of Africa For example: Ribose-5-Phosphate can be Some theories say that being deficient in this redirected into the glycolysis pathway through enzyme may be protective against malaria Ribulose-5-Phosphate, to Xylulose-5-Phosphate, x-linked recessive inheritance (typically males then Fructose-6-Phosphate. are the most affected) ○ REMEMBER: This pathway generates two NADPH ○ May cause the following: and substrates for nucleotide synthesis. Hemolytic Anemia After ingestion of anti-malarial medications The Pentose Phosphate Pathway generates NADPH, which is Can occur even after eating some fava beans important for oxidative stress homeostasis. (condition: favism) Things such as Oxidant stress (from drugs or metabolism) Any type of abnormal stress that can occur on can create hydrogen peroxide (superoxide/free the cell can actually cause a hemolytic radicals/oxidative stress). anemia because the cells are a little more The cell deals with this by way of NADPH. sensitive as they are deficient in this enzyme Neonatal hyperbilirubinemia (jaundice) Note: neonatal jaundice which is normal is called physiologic jaundice, which occurs between two to three days of birth or two to three days of age If the baby is becoming jaundiced within the first 24 hours of birth then you may want to check to see if this enzyme is deficient or not Once NADPH is generated from the pentose phosphate pathway, it can be utilized by an enzyme known as glutathione reductase ○ Oxidizes NADPH to NADP+ In the meantime, it’ll actually reduce oxidized glutathione into reduced glutathione 9  UNIT 3: CARBOHYDRATES AND ITS METABOLISMS GLYCOGENESIS PATHWAY Glycogenolysis is the process by which glycogen is converted back to glucose-6-phosphate for entry into the glycolytic pathway. GLYCOGENESIS (YOUTUBE VIDEO) Glyco means glycogen Genesis means formation ○ Basically the two words combined means “glycogen formation.” When we take a meal full of carbohydrates, it gets broken down to glucose and then glucose will be stored somewhere in the body which is the liver/muscle. The process of glucose converting to glycogen is “Glycogenesis” Glycogen is the storage form of glucose which is stored in the liver. This happens when the cell’s energy requirements are being met When your body is in a high energy state the extra energy is stored in the form of glucose. It is only in the liver that conversion of your glycogen can happen as well as for it to be glucose again (which is due to the presence Glycogen phosphorylase) Glucose is converted to Glucose-6-phosphate which is The liver also synthesizes glucose-6-phosphatase (which catalyzed by hexokinase (enzyme). without this enzyme, the glucose will be trapped in the Glucose-6-phosphate will be converted to glycolytic pathway.) Glucose-1-phosphate. The reaction is catalyzed by Our livers can give glycogen through the phosphoglucomutase. glucose-6-phosphate because of fasting. Glucose-1-phosphate is then converted to UDP Glucose. Glucose-6-phosphate is converted to This reaction is catalyzed by UDP Glucose phosphorylase. glucose-1-phosphate which is then converted to uridine ○ UDP Glucose is important for addition of pre-formed diphosphoglucose then to glycogen by glycogen synthase. glycogen polymers (which is denoted as “n”) The liver and the muscles are capable of the synthesis of UDP Glucose will be then converted to Glycogen (n) + glycogen. Hepatocytes are capable of releasing glucose UDP Glucose. from glycogen or other sources to maintain the blood Glycogen (n) + UDP Glucose will then be converted to glucose concentration. This is because the liver Glycogen (n + 1). synthesizes the enzyme glucose-6-phosphatase. Without this, glucose is trapped in the glycolytic pathway. Muscle cells do not synthesize glucose-6-phosphatase so they are incapable of dephosphorylating glucose. Once glucose enters a muscle cell, it remains as glycogen unless it is catabolized. Glycogen created in the muscle cells cannot transfer to other parts when fasting. Glycogenin ○ It is the reason why the preformed glycogen polymer appears 10  UNIT 3: CARBOHYDRATES AND ITS METABOLISMS ○ Structure: a dimer with subunit A and subunit B First phase: Glucose is converted into ○ The terminal position has a tyrosine group Glyceraldehyde-3-phosphate ○ Glucose moieties (UDP glucose) will attach to Since phosphate is involved, this means that at this tyrosine and more glucose moieties will attach to each point, energy is consumed rather than produced other continuously to form chain Second phase: Glyceraldehyde-3-phosphate is converted into pyruvate Energy is produced in this phase ○ Glycolysis reactions FIRST PHASE 1. Glucose is converted into glucose-6-phosphate Hexokinase (enzyme) catalyses this step Hexo: 6; Kinase: the group of enzymes that catalyses phosphorylation reactions ATP is consumed and converted into ADP, hence energy is consumed 2. Glucose-6-phosphate is converted into fructose-6-phosphate Isomerase (enzyme) catalyses this step Regulation (Glycogen synthase) This is a simple rearrangement of the molecule ○ Rate limiting enzyme for the last step in the pathway 3. Fructose-6-phosphate is converted into ○ Can have allosteric modification Fructose-1,6-bisphosphate ○ Has 2 forms: Catalysed by phospho-fructo kinase A form - not phosphorylated; active Another ATP is consumed and converted into ADP, B form - phosphorylated; inactive hence energy is consumed again at this step ○ Inactive to active form conversion is catalyzed by the 4. Fructose-1,6-bisphosphate is split into phosphoprotein phosphatase (which is regulated by glyceraldehyde-3-phosphate and dihydroxyacetone other hormones) phosphate Insulin activates phosphatase Catalyzed by aldolase Glucagon, epinephrine, and G6P hinders Up until this point, energy is consumed phosphatase Lipogenesis ○ Active to inactive form conversion is triggered by ○ Formation of fatty acids from carbohydrates glycogen synthase kinase (GSK) ○ If there is an excess of carbohydrates (this is also the Insulin inhibits GSK (active form doesn’t not get reason why we gain weight) converted) ○ Pathway from lipids to carbohydrate metabolism, excess glucose can enter into producing your lipids through lipo Link: https://www.youtube.com/watch?v=qza0_10DvtE genetic pathways (reversible) Lipolysis OTHER PATHWAYS ○ Decomposition of fats. Fatty acids can then be used for Glycolysis energy. This can also be source of glucose ○ Glucose is burned and converted into pyruvate or lactate for the production of energy SECOND PHASE ○ Pyruvate is the natural pathway for glycolysis ○ However, during starvation, lactate can be produced. GLYCERALDEHYDE-3-PHOSPHATE TO High lactate concentration would indicate starvation. This DIHYDROXYACETONE PHOSPHATE means that the carbohydrate intake is insufficient ○ Glyco: glucose; Lysis: breakdown ○ Is a metabolic pathway that involves a systematic breakdown of glucose to produce energy Glyceraldehyde-3-phosphate and dihydroxyacetone ○ Glycolysis occurs in the cytosol phosphate are isomers and can be interconverted into ○ Glucose (6 carbon molecule) is broken down into two each other by the enzyme isomerase pyruvate (3 carbon molecule) ○ But since glyceraldehyde 3-phosphate is further ○ This produces energy in the form of ATP and NADH utilized in the process of glycolysis, the equilibrium of ○ The pyruvate undergoes several other metabolic this isomerization reaction is always towards the pathways to produce more energy glyceraldehyde 3-phosphate ○ Two phases of Glycolysis: Every molecule of glucose is split into two molecules 11  UNIT 3: CARBOHYDRATES AND ITS METABOLISMS ○ Every reaction of the second phase happens twice and 3-PHOSPHOGLYCERATE TO 2-PHOSPHOGLYCERATE produces twice the products GLYCERALDEHYDE-3-PHOSPHATE TO 1-3 BISPHOSPHOGLYCERATE 3-phosphoglycerate is converted to 2-phosphoglycerate ○ This is a simple rearrangement reaction that happens with the help of the enzyme phosphoglycerate mutase Glyceraldehyde-3-phosphate is converted to 1-3 2-PHOSPHOGLYCERATE TO PHOSPHOENOLPYRUVATE bisphosphoglycerate ○ This involves the addition of a phosphate group at the first position of the phosphoglycerate ○ the enzyme that catalyzes this reaction is the glyceraldehyde-3-phosphate dehydrogenase A nicotinamide adenine dinucleotide (NAD), which is the coenzyme, is reduced to NADH, which is further utilized in the electron transport chain to produce more energy This reaction also utilizes a molecule of inorganic phosphate 2-phosphoglycerate is converted to 1-3 BISPHOSPHOGLYCERATE TO 3 PHOSPHOGLYCERATE phosphoenolpyruvate ○ The enzyme involved is enolase Magnesium ions are utilized in this reaction PHOSPHOENOLPYRUVATE TO PYRUVATE = 1-3 bisphosphoglycerate is converted to 3 phosphoglycerate by the enzyme phosphoglycerate kinase Phosphoenol pyruvate is converted to pyruvate by the ○ This kinase enzyme transfers the phosphate group at enzyme pyruvate kinase the first position of phosphoglycerate to adenosine The phosphate group at the phosphoenolpyruvate is diphosphate transferred to ADP and converted to ATP In this process a molecule of ATP is generated NET REACTION OF GLUCOSE One molecule of six carbon glucose splits into two molecules of three carbon compound pyruvate There is a net utilization of two ADP's 12  UNIT 3: CARBOHYDRATES AND ITS METABOLISMS ○ Since four ADP's are used in the second phase Control of blood glucose is under two major hormones: ○ Two ADP's are produced in the first phase insulin and glucagon, both produced by the pancreas. Their Two molecules of inorganic phosphate are utilized actions oppose each other. Two NAD+ are reduced to NADH molecules Other hormones and neuroendocrine substances also exert ○ During the conversion of glyceraldehyde 3-phosphate some control over blood glucose concentrations, permitting to 1-3 bisphosphoglycerate the body to respond to increased demands for glucose or to survive prolonged fasts. TABLE 14.1 PATHWAYS IN GLUCOSE METABOLISM ○ It also permits the conservation of energy as lipids when Pathway Description excess substrates are ingested. Metabolism of glucose molecule to Insulin Glycolysis pyruvate or lactate for production of ○ For regulation energy ○ Primary hormone responsible for glucose in the cell Formation of glucose-6-phosphate from ○ The hormone that decreases glucose in the blood Gluconeogenesis noncarbohydrate sources (such as amino Glucagon acids) ○ For regulation ○ Elevates glucose levels to bring it back to its normal Breakdown of glycogen to glucose for use Glycogenolysis value as energy Somatostatin Conversion of glucose to glycogen for Glycogenesis ○ Regulation of insulin and glucagon storage ○ Acts like a paracrine Conversion of carbohydrates to fatty Lipogenesis Epinephrine acids Cortisol Lipolysis Decomposition of fat Thyroxine Growth Hormone Dietary glucose and other carbohydrates either can be used by the liver and other cells for energy or can be stored as glycogen for later use. If glucose is low, the liver will use glycogen and other substrates to elevate blood glucose concentration (i.e. glycerol from triglycerides, lactic acid from skin and muscles, and amino acids). If lipolysis of triglycerides is unregulated, ketone bodies are formed, which can be used by the brain as a source of energy through the TCA cycle. The synthesis of glucose from amino acids is gluconeogenesis. This is used in conjunction with the formation of ketone bodies when glycogen stores are depleted—conditions normally associated with starvation. The principal pathway for glucose oxidation is through the Embden-Meyerhof pathway. (D - pancreas) Alpha cells in the pancreas are the source NADPH can be synthesized through the HMP shunt, which is of glucagons a side pathway from the anaerobic glycolytic pathway Majority of the cells are the Beta cells which produces and secretes insulin and is responsive to hyperglycemia CARBOHYDRATE METABOLISM REGULATION Delta cells produces the somatostatin and regulates The liver, pancreas, and other endocrine glands are all alpha and beta cells from secreting excess hormones involved in controlling the blood glucose concentrations within Pancreatic islets has endocrine functions a narrow range. Pancreatic peptide (PP) cells targets pancreatic acinar cells In carbohydrate metabolism regulation, only the endocrine Epsilon cells has something to do with satiety portion of the pancreas is focused on since the exocrine portion of it is for digestion. The endocrine portion of the pancreas is composed of alpha cells that produce glucagon, the beta cells which produce insulin, and the delta cells which stimulate the production of somatostatin. During a brief fast, glucose is supplied to the ECF from the liver through glycogenolysis. When the fasting period is longer than 1 day, glucose is synthesized from other sources through gluconeogenesis. 13  UNIT 3: CARBOHYDRATES AND ITS METABOLISMS INSULIN GLUCAGON BETA CELLS of the islets of Langerhans in the pancreas Primary hormone responsible for the entry of glucose into the cell Glucagon is the primary hormone responsible for Stimulus is hyperglycemia increasing glucose levels. If there is an increase in blood glucose levels, beta cells will ALPHA CELLS of the islets of Langerhans in the pancreas release insulin, this will cause the glucose level to return to Released during stress and fasting states normal. It enhances glycogenolysis in the liver Insulin will open up other cells and create glucose ○ If glycogen are lysed, the concentration of glucose will transporters so that it can enter the cells increase Cells will be bound by lipid membranes ○ If there is a decrease in blood glucose level, glucagon Glucose cannot pass through hydrophobic lipid membrane will be released from the alpha cells which would then It decreases plasma glucose levels by increasing the return the glucose level to normal transport entry of glucose in muscle and adipose tissue by Glucagon is a hyperglycemic agent because it causes the way of nonspecific receptors. increase of glucose concentration in the extracellular fluid Insulin is normally released when glucose levels are high It increases both glycogenolysis and gluconeogenesis and is not released when glucose levels are decreased. Glucagon can stimulate glycogenolysis. You’ll breakdown Insulin is the only hormone that decreases glucose levels. some of your glycogen stores and your liver will release Therefore, Insulin is a Hypoglycemic Agent some of this glucose into your blood. Remember that our Mechanism of Action brain cannot store so much glycogen so it is highly ○ Insulin increases the movement of glucose into the dependent on the glucose in our blood. That is why cells instead of the glucose remaining in the neurologic dysfunction is one of the earliest manifestations extracellular fluid of hypoglycemia. ○ It also increases and/or enhances glucose metabolism Remember, ATP is required to maintain the resting (glycolysis), lipogenesis, and glycogenesis (formation membrane potentials of our nervous tissue. So if there is of glucagon in the liver) little ATP, the sodium potassium ATPase pump won’t have ○ Particularly, it inhibits glycogenolysis anything to use therefore, your resting membrane potential Glycogenolysis: is the biochemical pathway in of our excitable tissues will become aberrant. The glucagon which glycogen breaks down into will try to help that by increasing the blood glucose levels to glucose-1-phosphate and glycogen normal that is why it’s hyperglycemic. ○ These are the actions of insulin to lower the glucose level in the extracellular fluid 14  UNIT 3: CARBOHYDRATES AND ITS METABOLISMS THE ACTION OF HORMONES SOMATOSTATIN Increases glycogenesis & glycolysis: glucose → glycogen → pyruvate → Insulin acetyl-CoA Increases lipogenesis Decreases glycogenolysis Increases glycogenolysis: glycogen → glucose Glucagon Increases gluconeogenesis: fatty acids → acetyl-CoA → ketone, proteins → amino acids “Supporting actor” From the DELTA CELLS of the islets of Langerhans in the INSULIN VS. GLUCAGON pancreas Regulates the alpha and beta cell secretion. It is somehow inhibitory. Increases plasma glucose ○ Regulates (inhibits) insulin and glucagon, growth hormone, and other endocrine hormones ○ Acts as a referee between insulin and glucagon EPINEPHRINE If there is an increase in glucose, pancreatic beta cell receptors will sense this and more insulin will be secreted. That insulin will then cause some of the glucose to enter the liver as well as the other cells, it will lower down the blood glucose. So glucose is converted to glycogen (storage form). If the glucose is low, it would be sensed by the pancreatic receptors, producing more glucagon. Liver will break down glycogen, releasing glucose to return your glucose level to normal. Hypoglycemia triggers alpha cells. The alpha cells secreting the glucagon will trigger glycogenolysis releasing some of the liver glucose into our bloodstream. Insulin and glucagon are antagonists Negative feedback maintains glucose concentration (homeostasis). Occurs when glucose levels are normal so glucagon and insulin production stops. Imbalance of glucose concentration may lead to various diseases (e.g. kidney disease, retinopathy, neuropathy, etc.) The pancreas will detect changes in glucose levels and will release hormones (insulin/ glucagon) to bring glucose concentrations back to normal From adrenal medulla (deeper portion of the adrenal gland) Increases blood glucose ○ Inhibits insulin ○ Increases glycogenolysis (Just like glucagon) ○ Promotes lipolysis (Lipids can be utilized as energy) Released in times of stress (to increase energy production; also known as adrenaline rush) Adrenal glands are located on the superior portion of the kidneys 15  UNIT 3: CARBOHYDRATES AND ITS METABOLISMS Adrenal medulla secretes epinephrine in response to decreasing blood glucose levels so it is a stress response. The hormones in the adrenal cortex also affects blood sugar control (see Cortisol). Aldosterone (glomerulosa of cortex) is responsible for salt control; reabsorb sodium & secrete potassium CORTISOL Primary stress hormone From adrenal cortex on stimulation of ACTH (Adrenocorticotropic Hormone; from the anterior pituitary gland) From the zona fasciculata of our adrenal cortex. The release of cortisol can either be from the ACTH or from hypoglycemia. It counter regulates hypoglycemia by increasing the glucose level of the blood. Decreased levels of cortisol stimulate the anterior pituitary to release ACTH. ACTH, in turn, stimulates the adrenal cortex to release From thyroid gland, stimulated by the production of cortisol. thyroid-stimulating hormone (TSH) Increases plasma glucose Increases plasma glucose ○ decreases intestinal entry into the cell (so it ○ Increases glycogenolysis, gluconeogenesis, and accumulates in the extracellular fluid) intestinal absorption of glucose ○ increases gluconeogenesis, liver glycogen, lipolysis, Thyroxine is a metabolic hormone, an increased and glycogenolysis metabolism would require a lot of energy so to source out the energy, it breaks down our glycogen stores, even our THYROXINE lipid and protein sources. Mechanism: People with hyperthyroid get thin very fast. There was a time when thyroid hormones (Bangkok pills containing thyroxine) increased metabolism. Increasing the breakdown of glycogen in the liver and the muscles, gluconeogenesis which also the breakdown of lipid stores, and intestinal absorption of glucose because it causes rapid peristaltic movement that is why some people get diarrhea. 16  UNIT 3: CARBOHYDRATES AND ITS METABOLISMS GROWTH HORMONE Delta Islets Somatostatin of Increases Inhibiting insulin Langerhans Note: insulin is the only hormone able to decrease blood glucose, whereas other hormones cause hyperglycemia. DISEASES ASSOCIATED WITH CARBOHYDRATES Hyperglycemia Hypoglycemia Blood sugar is considered too low if it is lower than 50 mg/dL when fasting There are also individuals who Blood sugar is categorized have 60 mg/dL blood sugar but too high if it is higher than are considered normal. 100 mg/dL when fasting Usually happens to individuals that follow crash diets (i.e. those who starve themselves or From anterior pituitary gland those who skip meals). Growth Hormone is responsive to hypoglycemia. Growth It tends to occur if you have not hormone secretion increases when you have eaten. But in a few cases, it hypoglycemia. also can occur after a meal Since your growth hormone wants to build up your body, It is more likely to occur after (postprandial hypoglycemia) if and with decreased glucose that will not be accomplished. meals you have had a gastric bypass Instead, the growth hormone will try to increases plasma surgery. Postprandial glucose by: Both have the same hypoglycemia can occur if your ○ Decreasing entry of glucose into the cells manifestations: neurologic body produces too much insulin ○ Increases glycolysis function and weakness. To (higher than you body needs) Its release from the pituitary is stimulated by decreased differentiate (without the after a meal. glucose levels and inhibited by increased glucose. capillary blood glucose test), ask the patient if they If a patient has a tumor such as CARBOHYDRATE METABOLISM REGULATION already had a meal. an insulinoma, it causes Hormone Source Effect Mechanism uncontrolled production of Increasing glycolysis, insulin, causing hypoglycemic Beta Islets entry of glucose episodes. Insulin of Decreases Inhibiting Langerhans In diabetics, it occurs when the glycogenolysis injection of insulin is over than Increasing Alpha Islets the body needs. Again, it is glycogenolysis in Glucagon of Increases more common in type-1 than in liver and Langerhans gluconeogenesis type-2. Inhibiting insulin In diabetes, it occurs when Adrenal secretion, the cells of the body are less Some anti-diabetic drugs can Epinephrine Increases medulla Increasing responsive to insulin (type-2 also cause hypoglycemia. glycogenolysis diabetes) or if there is lack of Increasing insulin in the bloodstream Glucose level of diabetic really Adrenal gluconeogenesis, Cortisol Increases (type-1 diabetes), as a result has to be monitored which is cortex lipolysis, and glycogenolysis glucose cannot be optimally why they have small gadgets to Increasing absorbed by cells of the check their blood sugar from glycogenolysis, body. time to time Thyroid gluconeogenesis, Thyroxine Increases gland and intestinal Type-1 diabetes: there is a absorption of tendency that blood sugar will glucose suddenly drop, which is why Anterior people with this disease usually Growth Decreases entry into Pituitary Increases Hormone cells carry candies with them or need Gland to consume sugar concentrate 17  UNIT 3: CARBOHYDRATES AND ITS METABOLISMS immediately when they feel ○ When there is a high concentration of solute, it attracts there is too much insulin action the solvent (water) (can cause shock) Ketones in serum and urine (ketonemia and ketonuria) ○ Glucose is not properly utilized, therefore, body resorts to Hypoglycemia is more other sources of glucose (stored fats) for energy dangerous than hyperglycemia. Decreased blood and urine pH (acidosis) The link between Electrolyte imbalance hyperglycemia and seizures ○ Caused by losses of sodium is not clear yet (still ○ Excessive loss due to Polyuria (in patients with diabetes debatable). mellitus) Increased volume of urine or frequent urination The reason is that you In the process, it loses other electrolytes together cannot utilize your glucose with the urine even if you have so much of There will be hyperkalemia (increased potassium it. Your body senses it and concentration due to displacement of potassium from then proceeds to get energy the cells in acidosis) It’s clear that hypoglycemia can from other sources such as be one of the trigger factors of DIABETES MELLITUS (DM) lipids. Prolonged lipolysis seizures. A group of metabolic disease characterized by hyperglycemia can produce ketones (acids). The theory is that due to: excess ketones would cause ○ Defects in insulin secretion and/or an acidic body environment Insulin deficiency especially in the CNS. This Insulin is able to decrease glucose concentration in affects the production of the extracellular fluid; neurotransmitters by E.g., muscles are unable to use glucose due to low increasing the production of insulin excitatory neurotransmitters, Glucose cannot enter cells such as those of the causing seizures. muscles and liver This is caused by the low levels of insulin in the HYPERGLYCEMIA blood, leading to an accumulation of glucose in Increased plasma glucose levels the circulation (hyperglycemia) ○ Caused by an imbalance of hormones ○ Defects in insulin action Normal individuals: insulin is secreted to lower the levels of Even if insulin levels are sufficient within the glucose. bloodstream, a defect in the insulin action prevents it ○ Insulin enhances membrane permeability to cells in the from functioning properly liver, muscle, and adipose tissue. Insulin receptor dysfunction ○ It also alters the glucose metabolic