Introduction
Glycolysis is a fundamental metabolic pathway where glucose is broken down. In the presence of oxygen (aerobic conditions), glucose is converted into pyruvic acid. However, in the absence of oxygen (anaerobic conditions) or in cells lacking mitochondria like red blood cells (RBCs), glucose is converted into lactic acid. This process generates ATP, the primary energy currency of cells.
Equation
The overall equation for glycolysis is:
СьН1206 + 602 + 32ADP3· + 32Р;2· → 6СО2 + 6Н2О + 32АТР+ + 320Н-
Location
Glycolysis takes place in the cytoplasm of all human cells. The liver, kidneys, and muscles exhibit particularly high rates of glycolysis.
Regulation
Glycolysis is tightly regulated to ensure efficient energy production and utilization. This regulation occurs through:
1. Enzymatic Regulation:
- Change in Enzyme Synthesis Rate:
- Induction: Increased enzyme synthesis rate at the gene expression level, leading to increased mRNA synthesis.
- Repression: Decreased enzyme synthesis rate at the gene expression level, leading to decreased mRNA synthesis.
- Covalent Modification: Reversible phosphorylation and dephosphorylation of enzymes.
- Allosteric Effect: Molecules binding to enzymes at sites other than the active site, influencing enzyme activity.
Four Key Regulatory Enzymes (Irreversible Reactions):
- Hexokinase
- Glucokinase
- Phosphofructokinase
- Pyruvate kinase
2. Hormonal Regulation:
- Insulin: Stimulates glycolysis.
- Glucagon: Inhibits glycolysis.
Inhibitors of Glycolysis
Several molecules can inhibit glycolysis:
- ARSENATE
- IODOACETATE: Inhibits glyceraldehyde-3-phosphate dehydrogenase by targeting its SH group.
- FLOURIDE: Inhibits enolase.
Clinical Importance: Formation of 2,3-BPG and Glycolytic Disorders
Formation of 2,3-Bisphosphoglycerate (2,3-BPG):
2,3-BPG is a byproduct of glycolysis that plays a crucial role in regulating oxygen release from hemoglobin in red blood cells.
Diseases Associated with Impaired Glycolysis:
- Hexokinase deficiency
- Pyruvate kinase deficiency: Can lead to hemolytic anemia.
- Lactic acidosis: Buildup of lactic acid due to anaerobic glycolysis.
Importance of Glycolysis:
- Anaerobic ATP Production: When oxygen supply is limited, glycolysis can still generate ATP, albeit less efficiently.
- Energy Source During Birth: Glycolysis is crucial for providing energy to newborns during labor and delivery.
- Tissue-Specific Energy Production: Some tissues rely heavily on glycolysis as their primary energy source.
ATP Yield of Glycolysis:
| Step | Reaction | Net ATP Gain |
|---|---|---|
| Glucose → Fructose-1,6-bisphosphate | 2 ATP | |
| Glyceraldehyde-3-phosphate dehydrogenase | 2(NADH → NAD+) | 6 ATP |
| Substrate-level phosphorylation (a) | 2-phosphoglycerate kinase | 2 ATP |
| Substrate-level phosphorylation (b) | Pyruvate kinase | 2 ATP |
| TOTAL | 12 ATP |
