ME03 - GLYCOLYSIS Flashcards
Major pathway for glucose metabolism
Glycolysis
Substrate and Product
Substrate: Glucose
Product: Pyruvate
Overall Reaction
Glucose + 2ADP + 2P»_space; 2Lactate or Pyruvate + 2 ATP + 2 H2O
Where does Glycolysis occur?
Cytoplasm of all cells
GLUT TRANSPORTERS
1 - Erythrocytes, BBB | Uptake of glucose
2- Liver, Pancreatic B Cells | Uptake of glucose
3- BRAIN, Neurons, Placenta | Uptake of glucose
4- Heart and Skeletal Muscle, Adipose Tissue | “Insulin-timulated uptake of Glucose”
5 - Small Intestine | Absorption of Fructose at luminal side of Small Intestine
Types of Glycolysis
Anaerobic - Cells without mitochondria (RBC, White Muscle
Final Product: Lactate | Lactic Acidosis
Aerobic - Cells with mitochondria and supply of O2
Final Product: Pyruvate
2 Stages of Glycolysis
- Energy Investment Phase - 2 ATPs Phosphorylation
2. Energy Generation Phase - 2 molecules of ATP are formed by substrate level phosphorylation (produce ATP)
Purpose of PO4
Trap Glucose inside the cells
Irreversible steps in Gycolysis
- Phosphorylation of Glucose
- Phosphorylation of fructose 6-phosphate (RATE LIMITING STEP)
- Formation of pyruvate
- Glucose»_space; Glucose 6P
Hexokinase vs Glucokinase
Hexokinase - in most tissues | Phosphorylate Glu, Fru, Gal | Inhibited by Glucose 6P | Low Km, Low Vmax | High affinity for glucose - UTILIZE ENERGY FIRST
Glucokinase - in liver parenchymal cells, islets of pancreatic cells | Phosphorylate glucose alone | Inhibited by Fructose 6P | High Km, High Vmax | Low affinity for Glucose
- HELPS STORE EXCESS ENERGY
- Fructose 6P»_space; Fructose 1,6BP
Enzyme: Phosphofructokinase
IRREVERSIBLE AND RATE-LIMITING STEP OF GLYCOLYSIS
Difference of PFK1 and PFK2
PFK1 - converts fructose 6P to fructose 1,6BP | Inhibited by ATP and citrate | Activated by Fructose 2,6BP (Most potent, via allosteric activation) and AMP
PFK2 - coverts fructose 6P to fructose 2,6BP | Inhibited by DEC insulin, INC glucagon (Starvation) | Activated by (Well-fed state) INC insulin DEC glucagon
- PEP»_space; Pyruvate
Substrate-level phosphorylation to yield 1 ATP per molecule of phosphoenolpyruvate
Enzyme: Pyruvate kinase
Activated by: Fructose 1,6BP
Inhibited by Phosphorylation, Which occurs when INC glucagon, INC cAMP
Steps involved in production of ATP
1,3BP»_space; 3 Phosphoglycerate (Phosphoglycerate kinase)
PEP»_space; Pyruvate (Pyruvate kinase)
Most common defect in Glycolysis
PK Deficiency
Manifest Chronic Hemolytic Anemia
Aldolase A deficiency can also cause Hemolytic Anemia
Px has low exercise capacity, particularly on HIGH CHO diets
Muscle Phosphofructokinase Deficiency
Role of NADH in Glycolysis
Oxidation of Glyceraldehyde 3 PO4»_space; 1,3BPG
Enzyme: Glyceraldehyde PO4 dehydrogenase
Possible fates of NADH
Enter malate-aspartate or G3P shuttle and be converted to ATP.
Can also convert pyruvate to Lactate
In AEROBIC GLYCOLYSIS, NADH is converted to ATP and trnasported using 2 shuttles
Malate-Aspartate Shuttle»_space; Yields 3 ATPs each (liver, kidney and heart)
Glycerol Phosphate Shuttle»_space; Yields 2 ATPs each (Skeletal muscle, brain)
In ANAEROBIC GLYCOLYSIS, Pyruvate is converted to Lactate by the action of
Lactate dehydrogenase
Possible fates of Pyruvate
RBCs, Lens, and Corneas of the Eye, Kidney Medulla, WBC, Testes
Synthesis of 2,3 BPG
Enzyme: Bisphosphoglycerate mutase
Fx: Binds to Hgb and cause shift to the R of the HgbO2 dissociation curve
Example: Chronic Hypoxia»_space; Reactive Polycythemia»_space; INC BPG mutase,»_space; INC 2,3 BPG»_space; SHIFT TO THE R
Pyruvate»_space; Acetyl CoA
Enzyme: Pyruvate Dehydrogenase complex with co-enzymes:
- Thiamine pyrophosphate
- FAD
- NAD+
- Coenzyme A (contains pantothenic acid)
- Lipoic acid
Pyruvate and Acetyl CoA is activated and inhibited by
Activated by: NAD+ CoA and pyruvate
Inhibited by: ATP, Acetyl CoA, NADH
Most common biochemical cause of congenital lactic acidoses, Brain is deprived of Acetyl CoA
Pyruvate Dehydrogenase Deficiency
Treatment: ketogenic diet
Inactivates PDH by binding to lipoic acid so it competes with inorganic phosphate as a substrate for glyceraldehyde 3P Dehydrogenase
Arsenic Poisoning
Prone to thalamine - deficiency and may develop potentially fatal pyruvate and lactic acidosis
Chronic alcoholism
ATP Yield in Aerobic and Anaerobic
ATPs in Substrate-Level Phosphorylation : 4 both
ATPs from NADH (aerobic 4-6) (anaerobic 0)
ATPs consumed (aerobic -2) (anaerobic -2)
Total (Aerobic - 6 or 8) (Anaerobic 2)