Carbohydrates III (PDF) - Melvin Berin, Biochemistry

CM 105: INTEGRATED BASIC SCIENCES BIOCHEMISTRY MOD...

CM 105: INTEGRATED BASIC SCIENCES BIOCHEMISTRY MOD 05 CARBOHYDRATES III MELVIN G. BERIN, M.D. | (01/20/2025) j OUTLINE Acetyl-CoA enters the citric acid cycle. I. Gluconeogenesis E. Role of fatty acids → Important for ATP generation in the process of oxidative II. Substrates V.Energy Requirements phosphorylation. A. Glycerol VI. Review Questions The process may also undergo the process of glycogenesis – B. Lactate VII.References glycogen synthesis which is a storage polymer in the skeletal C. Amino Acids IX.Appendix muscle and liver. III. Regulation of Pentose phosphate pathway is vital for it is a source of: Gluconeogenesis → reducing equivalents (NADPH) for fatty acid synthesis IV. Major pathways and → ribose for nucleotide and nucleic acid synthesis. regulation of gluconeogenesis Pyruvate and intermediates of the citric acid cycle: and glycolysis in the liver → carbon skeletons for amino acid synthesis. A. Glycolysis Gluconeogenesis B. Triglycerides/Triacylglycerol → the process of synthesizing glucose from noncarbohydrate C. Link of Anaerobic Glycolysis precursors such as lactate, amino acids, and glycerol. to Citric Acid Cycle D. Protein Catabolism to Glucose Must Know Lecturer Book Previous Trans I. GLUCONEOGENESIS The process of synthesizing glucose or glycogen from compounds other than carbohydrates. → Non-carbohydrate sources: ▪ lactate, glycerol, amino acids (except leucine and lysine) Major Organ Sites: Liver and Kidney Intracellular location: Cytoplasm and mitochondria During an overnight fast → Liver: 90% of gluconeogenesis → Kidneys: 10% of the newly synthesized glucose molecules After an overnight fast: → Glycogenolysis and gluconeogenesis: equal contributions to blood glucose ▪ As glycogen reserves are depleted, so gluconeogenesis becomes progressively more important. During prolonged fasting → Kidneys Figure 1. Overview of Carbohydrate Mechanism [Dr. Melvin Berin’s Lecture ▪ major glucose-producing organs Presentation] ▪ 40% of the total glucose production Important in organs that require a continuous supply of glucose as a metabolic fuel, such as: II. SUBSTRATES → Nervous system (brain), Erythrocytes (RBCs), kidney Gluconeogenic precursors are molecules that can be used to (specifically in renal medulla), lens and cornea of the eye, produce a net synthesis of glucose. testes, and exercising muscle Most important gluconeogenic precursors: Involves glycolysis, citric acid cycles, plus some special reactions → Glycerol Glycolysis and gluconeogenesis share the same pathway but in → Lactate opposite directions, and are reciprocally regulated → α-Keto acids obtained from metabolism of glucogenic amino → There are three irreversible reactions in glycolysis that acids. prevent simple reversal of glycolysis for gluconeogenesis ▪ All but two amino acids are glucogenic (leucine and lysine). ▪ Glucokinase (glucose to glucose-6-phosphate) A. GLYCEROL ▪ Phosphofructokinase-1(fructose-6-phosphate to Released during the hydrolysis of triacylglycerols (TAGs) in fructose-1,6-bisphosphate) adipose tissue. ▪ Pyruvate kinase (phosphoenolpyruvate to pyruvate) Delivered by the blood to the liver. Glycerol will become glucose. Glucose - the major fuel of most tissues derived from diet Phosphorylated to glycerol 3-phosphate via glycerol kinase and 1 A by the pathway of glycolysis. It is further derived or ATP. Glycerol + ATP- Glyurol-3 phosphate > - metabolized into: → Oxidized by glycerol 3-phosphate dehydrogenase to form * → Pyruvate - aerobically dihydroxyacetone phosphate (DHAP). Glycerol-3-phosphate + HAD DHAP + NADH - → Lactate - anaerobically ▪ Intermediate of glycolysis and gluconeogenesis. Accordingly, glucose further gets reduced to acetyl-CoA. → DHAP will then become Fructose 1,6 - bisphosphate. → a precursor of fatty acids and cholesterol such as steroid → Fructose 1,6 bisphosphate is converted to Fructose. hormones Phosphate via the enzyme Fructose 1,6 bisphosphatase.d CM 105 | IBS Carbohydrates III B3| Mariscotes, LM., Mesa, MJV.,, Ponce, KF., Pron, S., Quimson, HG., Rabadam, TG., Ravalo, PAGE 1 of 7 JA., Reyes, SR., Romasanta, SIM., Samarita, R., Silerio, H., Tercero, CJ., Valenzuela, NM., and Yongco, MC. BIOCHEMISTRY | MODULE 5: SPECIAL SENSES Carbohydrates III | Melvin G. Berin, M.D → Fructose 1,6 bisphosphate will then be converted to glucose Table 1. Non-essential and Essential Amino Acids Dr. Melvin Berin’s Lecture Presentation] 6 phosphate. → Before Glucose 6 phosphate can enter the ER as a glucose, Glucogenic Glucogenic Ketogenic the phosphate part should be removed, via glucose 6 and Ketogenic phosphatase.G Alanine B. LACTATE Arginine Asparagine Aspartate Cysteine Non Glutamate Tyrosine Essential Glutamine Glycine Proline Serine Histidine Phenylalanine Leucine Essential Methionine Isoleucine Lysine Threonine Tryptophan Valine Figure 2. The Lactic Acid (Cori Cycle) and Glucose-Alanine cycles. Arg is semi-essential, depending on the developmental stage Cori Cycle (Lactic Acid Cycle) → Involves the following steps: Mnemonics: ▪ Glucose uptake in peripheral tissues (muscle, RBCs, Non-essential Amino Acids: Ah, Almost All Girls Go Crazy After placenta, tumor) Guy Take Proposal Seriously ▪ Conversion of glucose to lactate via glycolysis. Essential Amino Acids: PriVaTe TIM HaLL ▪ Release of lactate into circulation. ▪ Lactate uptake by the liver. III. REGULATION OF GLUCONEOGENESIS ▪ Conversion of lactate back to glucose via gluconeogenesis. Role of Fructose 2, 6-bisphosphate Glucose-Alanine Cycle (Cahill Cycle) → Fructose 2, 6-bisphosphate is elevated when glucose is also → Occurs during the fasting state and plays a key role in elevated. maintaining blood glucose levels. → Regulates Glycolysis and Gluconeogenesis in the liver. → Provides an indirect mechanism for utilizing muscle glycogen → Most potent positive allosteric activator/stimulator of to sustain blood glucose during fasting. phosphofructokinase-1(PFK-1) in the liver. → Alanine production in skeletal muscles: ▪ PFK-1 stimulates glycolysis. ▪ During the fasting stage state, skeletal muscles release an → Most potent inhibitor of fructose 1, 6 bisphosphate in the liver excess amount of Alanine. Relieves inhibition of phosphofructokinase-1 by ATP, and ▪ Formed by transamination of pyruvate (from glycolysis of increases the affinity for fructose-6-phosphate. muscle glycogen). Concentration is under both substrate (allosteric) and hormonal ▪ Exported to the liver. control (covalent modification). → In the liver: Phosphofructokinase-2 functions: ▪ Alanine undergoes transamination back to pyruvate. → Has the kinase activity that phosphorylates fructose ▪ Pyruvate serves as a substrate for gluconeogenesis. 6-phosphate to form Fructose 2, 6-bisphosphate. → Role of amino acids: → Also has the phosphatase activity responsible for the ▪ Amino acids provide carbon for gluconeogenesis. breakdown of Fructose 2, 6-bisphosphate through ▪ Nitrogen from amino acids is converted to urea. dephosphorylation back to fructose 6-phosphate. → Alanine is the major gluconeogenic amino acid. → This bifunctional enzyme is under the allosteric control of → Energy requirements: fructose-6-phosphate. ▪ The ATP needed for hepatic gluconeogenesis is derived ▪ Stimulates the kinase from fatty acid oxidation. ▪ Inhibits the phosphatase C. AMINO ACIDS In feeding state (glucose is abundant): Major sources of glucose during fasting from tissue proteins. → Concentration of fructose 2,6-bisphosphate: increases. Their breakdown produces α-keto acids, such as: → Stimulates glycolysis by activating phosphofructokinase-1 and → Pyruvate inhibiting fructose 1,6-bisphosphatase. ▪ which is converted into glucose. → Fructose 1,6-bisphosphatase is inhibited by AMP—a → α-Ketoglutarate compound that activates phosphofructokinase-1. This results ▪ which enters the TCA cycle and forms oxaloacetate (OAA) in a reciprocal regulation of glycolysis and gluconeogenesis − OAA is a key precursor for phosphoenolpyruvate (PEP) in seen previously with fructose 2,6-bisphosphate. glucose production. → If the glucose level increase the fructose 2,6-bisphosphate also increase and it will stimulate the PFK-1= Glycolysis. Note: In the fasting state: Acetyl CoA and compounds that give rise only to acetyl CoA → Glucagon stimulates the production of cAMP. cannot give rise to a net synthesis of glucose. ▪ This activates cAMP dependent protein kinase. → Due to the irreversible nature of pyruvate dehydrogenase ▪ This in turn inactivates phosphofructokinase-2 and activates complex (PDHC) which converts pyruvate to acetyl CoA. fructose 2-6 bisphosphate by phosphorylation. → Give rise to ketone bodies (ketogenic). ▪ Hence, gluconeogenesis is stimulated by a decrease in the → E.g., acetoacetate, lysine, leucine concentration of fructose 2,6-bisphosphate. ↑ CM 105 | Integrated Basic Sciences (IBS) Carbohydrates III PAGE 2 of 7 BIOCHEMISTRY | MODULE 5: SPECIAL SENSES Carbohydrates III | Melvin G. Berin, M.D ↑ Glucose = ↑F-zin-BP = stimulate PFK-1 > Glycolysis - ↓ Glucose = ↓- F- 26 14 - = does not stimulate PFK-1- > Ghecomogenesis If the glucose level decrease the fructose 2,6-bisphosphate also STEP 4: ALDOLASE REACTION decrease, it will not stimulate PFK-1 = Gluconeogenesis. Table 5. Aldolase reaction Process Aldolase reaction Starting Substrate 2 molecules of G3P Enzyme Aldolase Product Fructose-1,6-bisphosphate (F1,6BP) STEP 5: DEPHOSPHORYLATION OF F1,6BP Table 6. Dephosphorylation of Fructose-1,6-bisphosphate Process Dephosphorylation Starting Substrate Fructose-1,6-bisphosphate Enzyme Fructose-1,6-bisphosphatase Product Fructose-6-phosphate Figure 3. Coordinate regulation of Phosphofructokinase-1 and Fructose 1,6-bisphosphatase [Lehninger Principles of Biochemistry, 5th edition] STEP 6: ISOMERIZATION Phosphofructokinase-1 → inhibited by adequate amounts of ATP and Citrate = Glycolysis Table 7. Isomerization of Fructose-6-phosphate is inhibited. Process Isomerization → Activated by ADP and AMP. signifies low energy levels - Starting Substrate Fructose-6-phosphate Fructose 1,6-bisphosphatase Enzyme Phosphoglucose isomerase → Inhibited by AMP = gluconeogenesis is inhibited. Product Glucose-6-phosphatase IV. MAJOR PATHWAYS AND REGULATION OF GLUCONEOGENESIS AND GLYCOLYSIS IN THE LIVER STEP 7: DEPHOSPHORYLATION OF G6P A. GLYCOLYSIS Gluconeogenesis in the liver and kidney uses the reversible Table 8. Dephosphorylation of Glucose-6-phosphate reactions from glycolysis, along with additional reactions to Process Dephosphorylation bypass the irreversible, non-equilibrium steps. → These non-equilibrium reactions are steps 1, 3, and 10, Starting Substrate Glucose-6-phosphate catalyzed by enzymes hexokinase, phosphofructokinase, and Enzyme Glucose-6-phosphatase pyruvate kinase, respectively, which prevent simple reversal of Product Glucose glycolysis for glucose synthesis. For glucose-6-phosphate (G6P) to become glucose, it needs to B. TRIGLYCERIDES/TRIACYLGLYCEROL enter the endoplasmic reticulum, where the enzyme Lipolysis breaks down triacylglycerol into its two main glucose-6-phosphatase dephosphorylates G6P to yield glucose and components: glycerol and fatty acids. phosphate. STEP 1: PHOSPHORYLATION OF GLYCEROL C. LINK OF ANAEROBIC GLYCOLYSIS TO CITRIC ACID CYCLE STEP 1: OXIDATION OF LACTATE TO PYRUVATE Table 2. Phosphorylation Of Glycerol Process Phosphorylation The product, pyruvate, will now move from the cytosol to Starting Substrate Glycerol mitochondria via a specific transporter protein called Enzyme Glycerol kinase mitochondrial pyruvate carrier (MPC). Product Glycerol-3-phosphate Table 9. Oxidation of Lactate STEP 2: OXIDATION OF GLYCEROL-3-PHOSPHATE Process Oxidation Starting Substrate Lactate Table 3. Oxidation of Glycerol-3-phosphate Enzyme Lactate Dehydrogenase Process Oxidation Product Pyruvate Starting Substrate Glycerol-3-phosphate Enzyme Glycerol-3-phosphate dehydrogenase STEP 2a: CARBOXYLATION OF PYRUVATE TO OXALOACETATE Product Dihydroxyacetone phosphate (DHAP) Table 10. Carboxylation of Pyruvate Process Carboxylation STEP 3: ISOMERIZATION OF DHAP Starting Substrate Pyruvate Table 4. Isomerization of Dihydroxyacetone phosphate Enzyme Pyruvate carboxylase Process Isomerization Product Oxaloacetate Starting Substrate Dihydroxyacetone phosphate STEP 2b: OXIDATIVE DECARBOXYLATION OF PYRUVATE TO Enzyme Triosephosphate isomerase ACETYL-CoA Product Glycerol-3-phosphate (G3P) To enter fatty acid synthesis, pyruvate must be converted to acetyl-CoA. This step acts as a bridge between citric acid cycle and fatty acid synthesis. CM 105 | Integrated Basic Sciences (IBS) Carbohydrates III PAGE 3 of 7 BIOCHEMISTRY | MODULE 5: SPECIAL SENSES Carbohydrates III | Melvin G. Berin, M.D Table 17. Dehydrogenation of Succinate Table 11. Oxidative Decarboxylation of Pyruvate Process Dehydrogenation Process Oxidative Decarboxylation Starting Substrate Succinate Starting Substrate Pyruvate Enzyme Succinate dehydrogenase Enzyme Pyruvate dehydrogenase Product Fumarate Product Acetyl-CoA STEP 9: HYDRATION OF FUMARATE TO MALATE STEP 3: CONDENSATION OF OXALOACETATE TO CITRATE Forms a carbon-carbon bond between the methyl carbon of Table 18. Hydration of Fumarate acetyl-CoA and the carbonyl carbon of oxaloacetate. Process Hydration Starting Substrate Fumarate Table 12. Oxidative Decarboxylation of Pyruvate Enzyme Fumarase (Fumarate hydratase) Process Condensation Product Malate Starting Substrate Oxaloacetate and Acetyl-CoA Enzyme Citrate synthase STEP 10: OXIDATION OF MALATE TO OXALOACETATE Product Citrate STEP 4: ISOMERIZATION OF CITRATE TO ISOCITRATE Table 19. Oxidation of Malate The reaction occurs in 2 steps: Process Oxidation → Dehydration to cis-aconitate. Starting Substrate Malate → Rehydration to isocitrate. Enzyme Malate dehydrogenase This provides integration of citric acid cycle activity and the Product Oxaloacetate (OAA) provision of citrate in the cytosol as a source of acetyl-CoA for fatty acid synthesis. D. PROTEIN CATABOLISM TO GLUCOSE Essential and Non- Essential Amino Acids Table 13. Isomerization of Citrate → Glucogenic Amino Acids can be converted to glucose. Process Isomerization → Ketogenic Amino Acids CANNOT be converted to glucose Starting Substrate Citrate because they form Ketones. Enzyme Aconitase (Aconitate hydratase) ▪ Ketogenic Amino Acids (Leucine and Lysine) will enter Product Isocitrate Pyruvate Dehydrogenase Complex (PDHC) to be converted to Acetyl Co- A. STEP 5: OXIDATIVE DECARBOXYLATION OF ISOCITRATE TO − Will not become glucose. ALPHA-KETOGLUTARATE − Instead, becomes energy as ATP and enter the Krebs Cycle. The decarboxylation requires Mg2+ or Mn2+ ions. Proteins can be converted to: → Pyruvate Table 14. Oxidative Decarboxylation of Isocitrate → Oxaloacetate Process Oxidative Decarboxylation → Alpha- ketoglutarate and Fumarate in the Krebs cycle Starting Substrate Isocitrate ▪ to form Malate and undergo further steps to become Enzyme Isocitrate dehydrogenase glucose. Product Alpha-ketoglutarate E. ROLE OF FATTY ACIDS The role of fatty acids in gluconeogenesis depends on whether it STEP 6: OXIDATIVE DECARBOXYLATION OF ALPHA is even-chain or odd-chain. KETOGLUTARATE TO SUCCINYL-CoA Even-chain fatty acids (FA) The alpha-ketoglutarate dehydrogenase complex requires the → Do not provide carbons for gluconeogenesis, however, its same cofactors as the pyruvate dehydrogenase complex— oxidation provides the ATP required for the process to occur. thiamine diphosphate, lipoate, NAD+, FAD, and CoA. ▪ FAs are oxidized to acetyl-CoA in the mitochondria which enters the TCA cycle. Table 15. Oxidative Decarboxylation of α-ketoglutarate ▪ Acetyl-CoA cannot be converted to pyruvate (essential for Process Oxidative Decarboxylation gluconeogenesis) as pyruvate dehydrogenase reaction is Starting Substrate α-ketoglutarate irreversible. Enzyme Alpha-ketoglutarate dehydrogenase complex ▪ For every two carbons of acetyl-CoA that enter the TCA Product Succinyl-CoA cycle, two carbons are released as CO2, therefore, there is no net synthesis of glucose from acetyl-CoA. STEP 7: HYDROLYSIS OF SUCCINYL-CoA TO SUCCINATE Odd-chain fatty acids (FA) This is the only example of substrate level phosphorylation in → The three carbons at the carbonyl-end of an odd-chain fatty the citric acid cycle. acid are converted to propionate. ▪ Propionate enters the TCA cycle as succinyl-CoA, which Table 16. Hydrolysis of Succinyl-CoA forms malate (an intermediate in glucose formation). Process Hydrolysis STEP 1: CARBOXYLATION OF PROPIONYL-COA TO Starting Substrate Succinyl-CoA D-METHYLMALONYL COA Enzyme Succinate thiokinase Product Succinate Table 20. Carboxylation of Propionyl CoA Process Carboxylation STEP 8: DEHYDROGENATION OF SUCCINATE TO FUMARATE Starting Substrate Propionyl CoA The enzyme contains FAD and iron-sulfur (Fe-S) protein, and Enzyme Propionyl CoA carboxylase directly reduces ubiquinone in the electron transport chain. Product D-Methylmalonyl Coa CM 105 | Integrated Basic Sciences (IBS) Carbohydrates III PAGE 4 of 7 BIOCHEMISTRY | MODULE 5: SPECIAL SENSES Carbohydrates III | Melvin G. Berin, M.D STEP 2: ISOMERIZATION OF D-METHYLMALONYL COA to I. REVIEW QUESTIONS L-METHYLMALONYL COA 1. Which of the following tissues is the primary site of gluconeogenesis during fasting? Table 21. Isomerization of D-Methylmalonyl CoA A. Muscle Process Isomerization B. Adipose tissue Starting Substrate D-Methylmalonyl CoA C. Liver Enzyme Methylmalonyl CoA racemase. D. Brain Product L-Methylmalonyl Coa 2. Which enzyme phosphorylates glycerol during gluconeogenesis? A. Glycerol dehydrogenase STEP 3: SYNTHESIS OF SUCCINYL CoA B. Glycerol kinase C. Pyruvate carboxylase Table 22. Synthesis of Succinyl CoA D. Phosphofructokinase Process Rearrangement reaction 3. Why can acetyl-CoA not be used for net glucose synthesis? Starting Substrate L-Methylmalonyl Coa A. Acetyl-CoA directly forms ketone bodies. Enzyme Methylmalonyl CoA mutase B. Pyruvate dehydrogenase is an irreversible reaction. Product Succinyl Coa C. Acetyl-CoA cannot enter the TCA cycle. D. Fatty acids are needed for acetyl-CoA formation. The succeeding reactions are the same with steps 7 to 10 of LINK 4. In the Cori cycle, which molecule is transported from the muscles OF ANAEROBIC GLYCOLYSIS TO CITRIC ACID CYCLE discussed to the liver? above. A. Glucose V. ENERGY REQUIREMENTS B. Lactate From Pyruvate C. Glycerol → Conversion of pyruvate to oxaloacetate by pyruvate D. Alanine carboxylase requires one ATP. → Conversion of oxaloacetate to phosphoenolpyruvate (PEP) by 5. Which enzyme is inactivated by glucagon to promote phosphoenolpyruvate carboxykinase (PEPCK) requires one gluconeogenesis? GTP (the energy equivalent of one ATP). A. Phosphofructokinase-2 fro Doc Bevin hand out → Conversion of 3-phosphoglycerate to 1,3-bisphosphoglycerate B. Glucokinase by phosphoglycerate kinase requires one ATP. C. Fructose 1,6-bisphosphatase → Since 2 moles of pyruvate are required to form 1 mole of D. Pyruvate kinase glucose, 6 moles of high-energy phosphate are required for the synthesis of 1 mole of glucose. 6. Which of the following best describes the role of fatty acids in From glycerol gluconeogenesis? → Glycerol enters the gluconeogenic pathway at the DHAP level. A. Fatty acids provide carbon for glucose synthesis. ▪ (1) Conversion of glycerol to glycerol-3-phosphate, which is B. Fatty acids provide ATP to drive gluconeogenesis. oxidized to DHAP, requires one ATP. C. Fatty acids directly convert to glucose. ▪ (2) Since 2 moles of glycerol are required to form I mole of D. Fatty acids do not play a role in gluconeogenesis. glucose, 2 moles of high-energy phosphate are required for 7. The energy required for gluconeogenesis from glycerol primarily the synthesis of I mole of glucose. Note: Fructose-2,6-bisphosphate (F2,6BP) is a regulatory comes from: molecule that is not part of the glycolysis pathways directly but A. The oxidation of fatty acids instead serves as a potent allosteric activator of B. The hydrolysis of triglycerides phosphofructokinase-1 (PFK-1). C. Glycogen breakdown Note: Fructose-1,6-bisphosphate (F1,6BP) on the other hand is D. Amino acid metabolism an intermediate in glycolysis. Its production is stimulated by the 8. The glucose-alanine cycle primarily involves: activity of PFK-1. A. Transport of glucose to muscles and alanine to the liver. Note: In muscles, pyruvate (produced from glycolysis) is converted to alanine via the enzyme alanine transaminase (ALT) by B. Transport of lactate to the liver for gluconeogenesis. accepting an amino group. Alanine is then transported through the C. Oxidation of alanine to urea in the liver. bloodstream to the liver, where it is also reconverted to pyruvate D. Deamination of alanine to generate pyruvate for glucose (during fasting). synthesis. VI. REFERENCES 9. What happens to the concentration of fructose 2,6-bisphosphate Dr. Melvin Berin’s lecture presentation (Carbohydrates IIII) during the fasting state? Harvey, R. A., & Ferrier, D. R. (2011). Lippincott's illustrated reviews: A. It increases to stimulate glycolysis. biochemistry, 5e. Lippincott Williams & Wilkins. Kennelly, P., Botham K., McGuinness, O., Rodwell, V. & Weil, P. A. B. It decreases to inhibit glycolysis and stimulate (2023) Harper's Illustrated Biochemistry (32nd ed.). McGraw-Hill gluconeogenesis. Education. C. It remains constant. Rodwell, Victor W, Bender, David A, Botham, Kathleen M, Kennelly, D. It is directly synthesized from glucose. Peter J, Weil, Anthony P. (2018). Harper's Illustrated Biochemistry 10. Which hormone promotes gluconeogenesis during fasting? (31st). New Delhi: McGraw Hill. A. Insulin Batch 2027 Lecture Trans (Carbohydrates 3 & 4) B. Glucagon C. Epinephrine D. Cortisol Answers: CBBBDBADBB CM 105 | Integrated Basic Sciences (IBS) Carbohydrates III PAGE 5 of 7 BIOCHEMISTRY | MODULE 5: SPECIAL SENSES Carbohydrates III | Melvin G. Berin, M.D VIII. APPENDIX Figure 4. Major pathways and regulation of gluconeogenesis and glycolysis in the liver [Dr. Melvin Berin’s Lecture Presentation] Highlights (1) entry points of glucogenic amino acids after transamination (marked by arrows from circles); (2) key gluconeogenic enzymes (within double-bordered boxes); (3) allosteric effects (wavy arrows); and covalent modifications by reversible phosphorylation (dashed arrows) CM 105 | Integrated Basic Sciences (IBS) Carbohydrates III PAGE 6 of 7 BIOCHEMISTRY | MODULE 5: SPECIAL SENSES Carbohydrates III | Melvin G. Berin, M.D Table 23. Comparison of Cori Cycle vs Glucose Alanine Cycle [Harper's Illustrated Biochemistry] Feature Cori Cycle (Lactic Acid Cycle Glucose-Alanine Cycle Primary Molecule Lactate Alanine Lactate is produced from anaerobic glycolysis in skeletal Alanine is formed in skeletal muscles via transamination of Source muscle, erythrocytes, or tissues lacking mitochondria. pyruvate, derived from glycolysis of muscle glycogen. Lactate is released into the blood and transported to the Alanine is released into the blood and transported to the Transport to Liver liver. liver. Lactate is oxidized to pyruvate and converted to glucose Alanine is transaminated back to pyruvate, which serves as Liver Metabolism via gluconeogenesis. a substrate for gluconeogenesis. The nitrogen from alanine is converted to urea in the liver Nitrogen Handling Not involved in nitrogen metabolism. and excreted. ATP for gluconeogenesis is derived from fatty acid ATP for gluconeogenesis is also derived from fatty acid Energy Source for Liver oxidation. oxidation. Recovers lactate produced during anaerobic metabolism Provides an indirect mechanism for muscle glycogen to Function and recycles it into glucose for energy. contribute to blood glucose maintenance during fasting. Active under anaerobic conditions (e.g., during intense Fasting State Predominantly active during fasting or starvation. exercise). Key Highlight: → Cori Cycle - focuses on lactate recycling from anaerobic glycolysis. → Glucose-Alanine Cycle - focuses on alanine metabolism as a source for gluconeogenesis, along with nitrogen removal. CM 105 | Integrated Basic Sciences (IBS) Carbohydrates III PAGE 7 of 7