WK8_GLYCOLYSIS-and-OXIDATION-PYRUVATE.docx.pdf

BIOCHEMISTRY GLYCOLYSIS and OXIDATION OF PYRUVATE Prepared by: Weeklings Lecturer: FARR KRIZHA I. TANGKUSAN, RN, MD Date: September 25, 2024 Objectives: Describe the pathway of glycolysis and its control. 1. Illustrate the reaction of pyru...

BIOCHEMISTRY GLYCOLYSIS and OXIDATION OF PYRUVATE Prepared by: Weeklings Lecturer: FARR KRIZHA I. TANGKUSAN, RN, MD Date: September 25, 2024 Objectives: Describe the pathway of glycolysis and its control. 1. Illustrate the reaction of pyruvate dehydrogenase and its regulation. 2. Explain how glycolysis operates in anaerobic conditions GLUT 4 Mnemonic: “FHM” – Fat, Heart, Muscle (Skeletal) GLYCOLYSIS What is it for? ✓ Major pathway for glucose metabolism that converts glucose into 3-C compounds to provide energy. ✓ Most common type: EmbdenMeyerhof-Parnas pathway Where does it occur? ✓ Cytosol What is the substrate? ✓ Glucose What are the end products? ✓ 2 molecules of either pyruvate or lactate Which step is rate-limiting? STEP 1: Phosphorylation of Glucose Fructose-6-phosphate→ Fructose-1,6-biphosphate ENZYME: Phosphofructokinase-1 Glucose enters glycolysis via phosphorylation (“activation”) 1st irreversible step of glycolysis Glucose-6-phosphate can enter other pathways: Gluconeogenesis, pentose phosphate pathway and glycogen metabolism SUBJECT 1 Prepared by: Date:  BIOCHEMISTRY GLYCOLYSIS and OXIDATION OF PYRUVATE Prepared by: Weeklings Lecturer: FARR KRIZHA I. TANGKUSAN, RN, MD Date: September 25, 2024 1. After meals, when postprandial blood glucose levels are high, liver glucokinase is significantly active, which causes the liver preferentially to trap and to store circulating glucose 2. When blood glucose falls to very low levels, tissues such as liver and kidney, which contain glucokinases do not continue to use glucose supplies that remain available 3. Tissues such as the brain, which are dependent on glucose, continue to scavenge blood glucose using STEP 4-5: Breakdown of fructose-1,6-phosphate their low Km hexokinases 4. The regulation of hexokinase and glucokinase activities is also different. Hexokinases I, II, and III are allosterically inhibited by product (G6P) accumulation 5. Glucokinases are not allosterically inhibited by G6P= insures liver accumulation of glucose stores during times of glucose excess, while favoring peripheral glucose utilization when glucose is required to supply energy to peripheral tissues. STEP 2: Isomerization of Glucose-6-phosphate 6-Carbon → 3-Carbon (x 2 molecules) STEP 6:Oxidation of glyceraldehyde phosphate to 1,3-bisphosphoglycerate Involves aldose-ketose isomerization STEP 3: : Phosphorylation of Fructose-6-Phosphate Accompanied by reduction of NAD+. STEP 7: Isomerization of Glucose-6-phosphate Phosphorylation by phosphofructokinase-1. 2nd irreversible step of glycolysis The rate-limiting step of glycolysis Phosphofructokinase: Inducible and allosterically regulated Phosphate group from 1,3-bisphosphoglycerate is transferred to ADP to form ATP (substrate-level phosphorylation) X 2 molecules = 2 ATP 2,3-bisphosphoglycerate (2,3-DPG) – intermediate formed; found in RBCs which affects O2-Hemoglobin dissociation SUBJECT 2 Prepared by: Date: BIOCHEMISTRY GLYCOLYSIS and OXIDATION OF PYRUVATE Prepared by: Weeklings Lecturer: FARR KRIZHA I. TANGKUSAN, RN, MD Date: September 25, 2024 STEP 8:Isomerization of 3- phosphoglycerate to 2-phosphoglycerate The Luebering-Rapoport pathway (or Involves isomerization by transferring a Rapaport-Luebering shunt) is a metabolic bypass phosphate group from 3-carbon to pathway in red blood cells (RBCs) that is crucial 2-carbon in regulating oxygen release from hemoglobin. STEP 9: Dehydration reaction Key features: 1. Location: This pathway occurs in red blood cells and is part of the glycolytic process. 2. Function: It generates 2,3-bisphosphoglycerate (2,3-BPG), a molecule that reduces the affinity of hemoglobin for oxygen, promoting oxygen Dehydration reaction forming release in tissues. phosphoenolpyruvate (PEP) Enolase – dependent on Mg2+ or Mn2+ 3. Bypass of Glycolysis: The Luebering-Rapoport ions; inhibited by F-. shunt allows RBCs to bypass the production of ATP in one step of glycolysis, temporarily STEP 10: Formation of Pyruvate diverting 1,3-bisphosphoglycerate into the production of 2,3-BPG by the enzyme bisphosphoglycerate mutase. 4. Enzyme Involvement: ○ Bisphosphoglycerate mutase: Converts 1,3-BPG to 2,3-BPG. ○ 2,3-BPG phosphatase: Converts 2,3-BPG back to 3-phosphoglycerate, allowing the continuation of glycolysis. Transfer of phosphate group from PEP to ADP to form ATP (substrate level phosphorylation). Availability of O2 determines whether the next pathways are: Aerobic conditions Anaerobic conditions Regulation: Activated by fructose-1,6-biphosphate Inhibited by glucagon SUBJECT 3 Prepared by: Date: BIOCHEMISTRY GLYCOLYSIS and OXIDATION OF PYRUVATE Prepared by: Weeklings Lecturer: FARR KRIZHA I. TANGKUSAN, RN, MD Date: September 25, 2024 OVERVIEW OF GLYCOLYSIS TWO TYPES GLYCOLYSIS Aerobic Glycolysis Anaerobic Glycolysis Cells with mitochondria Cells without Cells with adequate O2 mitochondria Cells without sufficient O2 End-product: PYRUVATE End-product: LACTATE ANAEROBIC CONDITIONS 3 Important NADH is used to reduce pyruvate to lactate Major fate of pyruvate in lens and cornea of the eye, kidney medulla, testes, RBCs and WBCs Lactic Acidosis is seen in vigorous exercise, septic shock, and cancer cachexia 3 IMPORTANT STEPS OF GLYCOLYSIS AEROBIC CONDITIONS Step 1: Phosphorylation of glucose Pyruvate is transported into the Step 2: Phosphorylation of fructose-6-phosphate mitochondria Undergoes oxidative decarboxylation to Acetyl-CoA by pyruvate dehydrogenase ○ NADH formed from glycolysis then enter the ETC. NADH cannot pass through the inner mitochondrial membrane, and thus requires Step 3: Formation of pyruvate shuttles for transport. SUBJECT 4 Prepared by: Date: BIOCHEMISTRY GLYCOLYSIS and OXIDATION OF PYRUVATE Prepared by: Weeklings Lecturer: FARR KRIZHA I. TANGKUSAN, RN, MD Date: September 25, 2024 SUMMARY ATP yield in Glycolysis What’s the role of converts glucose to either glycolysis? 2 molecules pyruvate or 2 molecules of lactate When is it Glycolysis is active during activated? the well-fed state, after a meal. Because that is when your glucose is high in the body. Oxidation of pyruvate What is the Glucose substrate? What is the Pyruvate or lactate product? When do you The present of undergo AEROBIC Mitochondira and enough GLYCOLYSIS? O2 When do you No Mitochondria and no undergo sufficient O2 ANAEROBIC GLYCOLYSIS? What are the 3 -Step 1 phosphorylation of important steps of glucose PYRUVATE DEHYDROGENASE COMPLEX glycolysis? - Step 3 phosphorylation of Enzyme complex system that oxidizes pyruvate fructose-6-phosphate to acetyl-CoA Coenzyme/Cofactors: -Step 10 formation of 1. Thiamine pyrophosphate (from vitamin B1) pyruvate (pyruvate kinase) 2. FAD (from vitamin B2) 3. NAD+ (from vitamin B3) What is the 2 in anaerobic per glucose 4. Coenzyme A (contains pantothenic acid) (from energy yield? molecule vitamin B5) 5. Lipoic Acid (antioxidant) 5/7 in aerobic glycolysis per glucose molecule Mnemonic- Thiamine -TENDER Lipoic Acid -LOVING CoA -CARE of a FAD -Filipina NAD+ -Nurse SUBJECT 5 Prepared by: Date: