Lipid Metabolism PDF

LIPID METABOLISM No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  Topics 1. Digestion and absorption of lipids 2. Triacylglycerol storage and...

LIPID METABOLISM No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  Topics 1. Digestion and absorption of lipids 2. Triacylglycerol storage and mobilization 3. Glycerol metabolism 4. Oxidation of fatty acids 5. ATP production from fatty acid oxidation 6. Ketone bodies and ketogenesis 7. Biosynthesis of fatty acids 8. Relationships between lipogenesis and citric acid cycle intermediates 9. Fate of fatty acid-generated Acetyl CoA 10. Relationships between lipid and carbohydrate metabolism 11. B vitamins and lipid metabolism No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  1. Digestion and Absorption of Dietary Lipids The first step in the digestion of triacylglycerols and phospholipids begins in the mouth as lipids encounter saliva. Chewing with the action of emulsifiers enables the digestive enzyme (lipase) to do their tasks. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  Digestion and Absorption of Dietary Lipids As a result, the fats become tiny droplets and separate from the watery components. In the stomach, gastric lipase starts to break down triacylglycerols into diglycerides and fatty acids. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  Digestion and Absorption of Dietary Lipids As stomach contents enter the small intestine, bile combines the separated fats with its own watery fluids. Bile contains bile salts, lecithin, and substances derived from cholesterol, so it acts as an emulsifier. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  Digestion and Absorption of Dietary Lipids As pancreatic lipase enters the small intestine, it breaks down the fats into free fatty acids and monoglycerides. Bile salts envelop the fatty acids and monoglycerides to form micelles. In a fatty acid micelle, the hydrophobic chains of the fatty acids and monoacylglycerols are in the interior of the micelle. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  Lipid Metabolism No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health 9-2 Triacylglycerol Storage And Mobilization Most cells in the body have limited capability for storage of TAGs. However, this activity is the major function of specialized cells called adipocytes, found in adipose tissue.  9-2 Triacylglycerol Storage And Mobilization An adipocyte is a triacylglycerol-storing cell. Adipose tissue is tissue that contains large numbers of adipocyte cells. Structural characteristics of an adipose cell No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9-2 Triacylglycerol Storage And Mobilization No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9-2 Triacylglycerol Storage And Mobilization 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. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9-2 Triacylglycerol Storage And Mobilization 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. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health.3 Glycerol Metabolism Glycerol metabolism primarily involves processes considered in the previous chapter. After entering the bloodstream, glycerol travels to the liver or kidneys, where it is converted, in a two-step process, to dihydroxyacetone phosphate. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9-3 Glycerol Metabolism The first step involves phosphorylation of a primary hydroxyl group of the glycerol. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9-3 Glycerol Metabolism In the second step, glycerol’s secondary alcohol group (C-2) is oxidized to a ketone. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9-3 Glycerol Metabolism The following equation represents the overall reaction for the metabolism of glycerol: No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  4. Oxidation of Fatty Acids There are three parts to the process by which fatty acids are broken down to obtain energy. 1. The fatty acids must be activated by bonding to coenzyme A. 2. The fatty acid must be transported into the mitochondrial matrix by a shuttle mechanism. 3. The fatty acid must be repeatedly oxidized, cycling through a series of four reactions, to produce acetyl CoA, FADH2, and NADH. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9-4 Fatty Acid Activation The outer mitochondrial membrane is the site of fatty acid activation, the first stage of fatty acid oxidation. Here the fatty acid is converted to a high-energy derivative of coenzyme A. Reactants are the fatty acid, coenzyme A, and a molecule of ATP. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9-4 Fatty Acid Activation The activated fatty acid–CoA molecule is called acyl CoA. The difference between the designations acyl CoA and acetyl CoA is that acyl refers to a random-length fatty acid carbon chain that is covalently bonded to coenzyme A, whereas acetyl refers to a two-carbon chain covalently bonded to coenzyme A. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  Fatty Acid Transport 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. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  Reactions of the β-Oxidation Pathway 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. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  Reactions of the β-Oxidation Pathway For a saturated fatty acid, the β-oxidation pathway involves the following functional group changes at the β carbon and the following reaction types. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  Step 1: Oxidation (dehydrogenation) Hydrogen atoms are removed from the a and b carbons, creating a double bond between these two carbon atoms. FAD is the oxidizing agent, and a FADH2 molecule is a product. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  Step 2: Hydration A molecule of water is added across the trans double bond, producing a secondary alcohol at the β-carbon position. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  Step 3: Oxidation (dehydrogenation) The β-hydroxy group is oxidized to a ketone functional group with NAD+ serving as the oxidizing agent. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  Step 4: Chain Cleavage The fatty acid 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. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  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-carbon-shorter 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. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  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. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  5. ATP PRODUCTION FROM FATTY ACID OXIDATION Let us calculate ATP production for the oxidation of a specific fatty acid molecule, stearic acid (18:0), and compare it with that from glucose. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  Figure on the left 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. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  Gross ATP = 122 ATP Fatty Acid Activation = 2 ATP Net ATP Production = 122 – 2 ATP = 120 ATP No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  Problem Solving What is the net ATP production for the complete oxidation of lauric acid, the C12 saturated fatty acid, to CO2 and H2O? No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  Solution Net ATP Production = (80 – 2) ATP = 78 ATP No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  6. 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. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9-6 Ketone Bodies Certain body conditions upset the lipid–carbohydrate balance required for acetyl CoA generated by fatty acids to be processed by the citric acid cycle. 1. Dietary intake high in fat and low in carbohydrates No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9-6 Ketone Bodies 2. diabetic conditions, where the body cannot adequately process glucose even though it is present 3. prolonged fasting conditions, including starvation. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9-6 Ketone Bodies A ketone body is one of three substances produced from acetyl CoA when an excess of acetyl CoA from fatty acid degradation accumulates because of triacylglycerol– carbohydrate metabolic imbalances. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9-6 Ketone Bodies Chemically, these three structures are closely related. The relationships are most easily seen if the focus starts with the molecule acetoacetate. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9-6 Ketone Bodies Reduction of the ketone group present in acetoacetate to a secondary alcohol produces β-hydroxybutyrate No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9-6 Ketone Bodies Decarboxylation of acetoacetate produces acetone. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health 9-6 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. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  Items to consider about this process prior to looking at the actual steps in this four-step process are: 3. Some of the acetoacetate produced in Step 3 is converted to the second ketone body,β-hydroxybutyrate, in Step 4 of ketogenesis.. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  Items to consider about this process prior to looking at the actual steps in this four-step process are: 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. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  Items to consider about this process prior to looking at the actual steps in this four-step process are: 5. Acetoacetate is somewhat unstable and can spontaneously or enzymatically lose its carboxyl group to form acetone. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  Items to consider about this process prior to looking at the actual steps in this four-step process are: 6. The ketone body acetone present in the bloodstream is a volatile substance that is mainly excreted by exhalation. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  Items to consider about this process prior to looking at the actual steps in this four-step process are: 7. The amount of acetone present is usually small compared to the concentrations of the other two ketone bodies. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  THE PROCESS OF KETOGENESIS Step 1: First Condensation Ketogenesis begins as two acetyl CoA molecules combine to produce acetoacetyl CoA, a reversal of the last step of the β-oxidation pathway. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  Step 2: Second Condensation Acetoacetyl CoA then reacts with a third acetyl CoA and water to produce 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) and CoA—SH. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  Step 3: Chain Cleavage HMG-CoA is then cleaved to acetyl CoA and acetoacetate No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  Step 4: Reduction Acetoacetate is reduced to b-hydroxybutyrate. The reducing agent is NADH. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  Exercise 1 2 Identify the missing 3 compound for each item shown on the right side. 4 6 5 No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  7. Lipogenesis is the metabolic pathway by which fatty acids are synthesized from acetyl CoA. is not simply a reversal of the steps for degradation of fatty acids (the β-oxidation pathway). No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  Features of Lipogenesis LIPOGENESIS LIPOLYSIS 1. Lipogenesis occurs in the cell cytosol 1. Degradation of fatty acids occurs in the 2. Lipogenesis enzymes are collected into a mitochondrial matrix. multienzyme complex called fatty acid 2. The enzymes involved in fatty acid degradation synthase. are not physically associated, so the reaction steps 3. Lipogenesis intermediates are bonded to are independent. ACP (acyl carrier protein). 3. The carrier for fatty acid degradation intermediates 4. Fatty acid synthesis is dependent on the is CoA. reducing agent NADPH. 4. Fatty acid degradation is dependent on the 5. Fatty acids are built up two carbons at a time oxidizing agents FAD and NAD+. during synthesis 5. Fatty acids are broken down two carbons at a time 6. In lipogenesis, acetyl CoA is used to form during degradation. malonyl ACP, which becomes the carrier of 6. CoA derivatives are involved in all steps of fatty No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health the two carbon units. acid degradation. WHEN DOES LIPOGENESIS OCCURS? Lipogenesis occurs in well fed condition. Conditions Favoring Lipogenesis Excess of Free Glucose after heavy Carbohydrate meals. Insulin promotes Lipogenesis  WHERE DOES LIPOGENESIS OCCUR? Predominant site for Lipogenesis Liver Cytoplasm Other tissues for Lipogenesis Intestine Mammary glands No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  REASONS FOR LIPOGENESIS Free excess Glucose can't be stored as it is in body cells and tissues. Free excess Glucose is first converted and stored in the form of Glycogen. Storage of Glycogen is limited. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  In a well-fed condition after limited storage of Glycogen When still there remains Free excess Glucose This free excess Glucose is Oxidized to Pyruvate via Glycolysis Further Pyruvate to Acetyl-CoA via PDH complex reaction This Acetyl-CoA when excess is then diverted for Lipogenesis. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  TRIACYLGLYCEROLS (TAG) To transform free excess Glucose to Acetyl-CoA further into Fatty acids. Fatty acids are stored as TAG Storageable form of Lipid (TAG). TAG in Adipocytes can be stored in unlimited amounts. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  LIPOGENESIS ACP Complex Formation Chain Elongation No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  ACP Complex Formation No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  ACETYL ACP FORMATION No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  MALONYL ACP FORMATION Carboxylation 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. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  MALONYL ACP FORMATION The malonyl CoA so produced then reacts with ACP to produce malonyl ACP. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  Chain Elongation No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  STEP 1: CONDENSATION ACETYL ACP AND MALONYL ACP CONDENSE TOGETHER TO FORM ACETOACETYL ACP. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  STEP 2: FIRST HYDROGENATION THE KETO GROUP OF THE ACETOACETYL COMPLEX, WHICH INVOLVES THE β-CARBON ATOM, IS REDUCED TO THE CORRESPONDING ALCOHOL BY NADPH. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  STEP 3: DEHYDRATION THE ALCOHOL PRODUCED IN STEP 2 IS DEHYDRATED TO INTRODUCE A DOUBLE BOND INTO THE MOLECULE (BETWEEN THE α AND β CARBONS) No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  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 No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  8. RELATIONSHIPS BETWEEN LIPOGENESIS AND CITRIC ACID CYCLE INTERMEDIATES No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9.8 Relationships Between Lipogenesis And Citric Acid Cycle Intermediates The intermediates in the last four steps of the citric acid cycle are all C4 molecules No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9.8 Relationships Between Lipogenesis And Citric Acid Cycle Intermediates The last four intermediates of the citric acid cycle bear the following relationship to each other. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9.8 Relationships Between Lipogenesis And Citric Acid Cycle Intermediates The intermediate C4 carbon chains of lipogenesis bear the following relationship to each other. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  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. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9. FATE OF FATTY ACID- GENERATED ACETYL COA No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9.9 Fate Of Fatty Acid-Generated Acetyl CoA 1. CITRIC ACID CYCLE (KREBS CYCLE) Acetyl-CoA enters the citric acid cycle, where it combines with oxaloacetate to form citrate. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9.9 Fate Of Fatty Acid-Generated Acetyl CoA 1. CITRIC ACID CYCLE (KREBS CYCLE) Through a series of enzymatic reactions, citrate is converted back to oxaloacetate, producing ATP, NADH, and FADH2, which are used for energy production. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9.9 Fate Of Fatty Acid-Generated Acetyl CoA 2. KETOGENESIS In the liver, during periods of low carbohydrate availability (e.g., fasting, low-carbohydrate diets, or uncontrolled diabetes), acetyl-CoA is converted into ketone bodies (acetoacetate, beta- hydroxybutyrate, and acetone). No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9.9 Fate Of Fatty Acid-Generated Acetyl CoA 2. KETOGENESIS Ketone bodies can be used as an alternative energy source by peripheral tissues, including the brain, during prolonged fasting or carbohydrate restriction. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9.9 Fate Of Fatty Acid-Generated Acetyl CoA 3. CHOLESTEROL SYNTHESIS Acetyl-CoA is the starting material for the biosynthesis of cholesterol. The process begins with the conversion of acetyl-CoA into HMG-CoA (3-hydroxy-3-methylglutaryl-CoA), which is then reduced to mevalonate by the enzyme HMG- CoA reductase. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9.9 Fate Of Fatty Acid-Generated Acetyl CoA 3. CHOLESTEROL SYNTHESIS Mevalonate undergoes a series of reactions to eventually form cholesterol, a vital component of cell membranes and precursor for steroid hormones and bile acids. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9.9 Fate Of Fatty Acid-Generated Acetyl CoA 4. FATTY ACID SYNTHESIS Although acetyl-CoA is produced from fatty acids during oxidation, it can also be used for fatty acid synthesis. In the cytoplasm, acetyl-CoA is converted into malonyl-CoA by acetyl-CoA carboxylase. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9.9 Fate Of Fatty Acid-Generated Acetyl CoA 4. FATTY ACID SYNTHESIS Malonyl-CoA is then used in the fatty acid synthase complex to elongate fatty acid chains, producing palmitate, which can be further modified into other fatty acids. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9.9 Fate Of Fatty Acid-Generated Acetyl CoA 4. AMINO ACID SYNTHESIS Acetyl-CoA serves as a precursor for the synthesis of certain amino acids and other important biomolecules. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9.9 Fate Of Fatty Acid-Generated Acetyl CoA 4. AMINO ACID SYNTHESIS For example, acetyl-CoA can be used in the production of the amino acid leucine or in the formation of acetylcholine, a neurotransmitter. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  10. RELATIONSHIPS BETWEEN LIPID AND CARBOHYDRATE METABOLISM No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9.10 Relationships Between Lipid And Carbohydrate Metabolism 1. Oxidation in the citric acid cycle. Both lipids (fatty acids and glycerol) and carbohydrates (glucose) supply acetyl CoA for the operation of this cycle. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9.10 Relationships Between Lipid And Carbohydrate Metabolism 2. Ketone body formation. This process is of major importance when there is imbalance between lipid and carbohydrate metabolic processes. The imbalance is caused by inadequate glucose metabolism during times of adequate lipid metabolism. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9.10 Relationships Between Lipid And Carbohydrate Metabolism 3. Fatty acid biosynthesis. The buildup of excess acetyl CoA when dietary intake exceeds energy needs leads to accelerated fatty acid biosynthesis. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9.10 Relationships Between Lipid And Carbohydrate Metabolism 4. Cholesterol biosynthesis. As with fatty acid biosynthesis, cholesterol biosynthesis occurs primarily when the body is in an acetyl CoA–rich state. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  11. B VITAMINS AND LIPID METABOLISM No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9.11 B Vitamins and Lipid Metabolism Thiamine is a precursor for the coenzyme thiamine pyrophosphate (TPP), which is essential for the pyruvate dehydrogenase complex. This complex converts pyruvate (from glycolysis) into acetyl-CoA, which is necessary for entering the citric acid cycle and lipid synthesis. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9.11 B Vitamins and Lipid Metabolism Riboflavin is a component of the coenzymes FAD (flavin adenine dinucleotide) and FMN (flavin mononucleotide). These coenzymes are crucial in the beta-oxidation of fatty acids, where they participate in the dehydrogenation steps, helping to generate acetyl- CoA from fatty acids. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9.11 B Vitamins and Lipid Metabolism Niacin is converted into NAD+ (nicotinamide adenine dinucleotide) and NADP+ (nicotinamide adenine dinucleotide phosphate), which are key coenzymes in oxidation-reduction reactions. NAD+ is required for the oxidation of fatty acids during beta-oxidation, while NADP+ is involved in the synthesis of fatty acids. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9.11 B Vitamins and Lipid Metabolism Niacin is converted into NAD+ (nicotinamide adenine dinucleotide) and NADP+ (nicotinamide adenine dinucleotide phosphate), which are key coenzymes in oxidation-reduction reactions. NAD+ is required for the oxidation of fatty acids during beta-oxidation, while NADP+ is involved in the synthesis of fatty acids. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9.11 B Vitamins and Lipid Metabolism Pyridoxine is involved in amino acid metabolism, which intersects with lipid metabolism, particularly in the production of carnitine, a molecule necessary for transporting fatty acids into the mitochondria for beta-oxidation. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9.11 B Vitamins and Lipid Metabolism Biotin is a coenzyme for carboxylase enzymes, such as acetyl-CoA carboxylase, which is critical in the first step of fatty acid synthesis. It is also involved in the catabolism of odd-chain fatty acids, which require the conversion of propionyl-CoA to succinyl-CoA. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9.11 B Vitamins and Lipid Metabolism Folate is involved in the transfer of one-carbon units during the synthesis of nucleotides and amino acids. Its role in lipid metabolism is more indirect, influencing homocysteine levels, which can affect cardiovascular health and lipid profiles. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health  9.11 B Vitamins and Lipid Metabolism Cobalamin is necessary for the conversion of methylmalonyl-CoA to succinyl-CoA, a critical step in the catabolism of odd-chain fatty acids. This reaction prevents the accumulation of methylmalonic acid, which could otherwise disrupt lipid metabolism. No part of this presentation may be reproduced or shared in any manner without the written permission of National University - College of Allied Health