Lecture 19: Glycolysis Overview

Lecture 19: Glycolysis

• Glycolysis is a metabolic pathway in the cytoplasm of cells. It breaks down glucose for energy (ATP) and intermediates for other metabolic processes.
• Specific objectives for the lecture include understanding the glycolytic pathway of glucose and the hormonal regulation of glycolysis.
• Glucose transport into cells happens via two mechanisms:
  • Na+-independent facilitated diffusion transport (mediated by a family of 14 glucose transporters). Examples include GLUT-1 (abundant in erythrocytes and blood brain barrier), GLUT-2 (liver cells), GLUT-3 (neurons), and GLUT-4 (adipose and skeletal muscle). Insulin stimulates GLUT-4.
  • Na+-monosaccharide co-transporter system (SGLT) requires energy and transports glucose against its concentration gradient in cells of the intestine, renal tubules, and choroid plexus.
• Aerobic glycolysis converts glucose to pyruvate in cells with mitochondria and adequate oxygen.
• Anaerobic glycolysis converts glucose to lactate without oxygen. This process generates ATP in tissues lacking mitochondria or those with insufficient oxygen (e.g., red blood cells).
• Important enzymes in glycolysis:
  • Hexokinase: In most tissues, the phosphorylation of glucose. It has a high affinity (low Km) for glucose but low capacity (low Vmax).
  • Glucokinase: In liver parenchymal cells and β cells of the pancreas. Acts as a glucose sensor, determining the threshold for insulin secretion in β cells and facilitating glucose phosphorylation in the liver during hyperglycemia (higher Km than hexokinase).
  • PFK-1 (phospho-fructokinase-1): The most important control point and rate-limiting step of glycolysis. It is inhibited by ATP and citrate and activated by AMP.
  • Pyruvate kinase: Catalyzes the conversion of phosphoenol pyruvate (PEP) to pyruvate, and in turn ATP formation.
• Anaerobic glycolysis produces two ATP per glucose, with no net production or consumption of NADH.
• Aerobic glycolysis produces 8 ATP per glucose molecule, due to 2 ATP directly, and 2NADH each contributing to 3 more ATPs via the electron transport chain.
• Hormonal regulation of glycolysis:
  • Glucagon inhibits glycolysis by inhibiting key enzymes glucokinase, phosphofructokinase-1, and pyruvate kinase, mainly in liver cells.
  • Insulin stimulates glycolysis by stimulating key enzymes.
• Pyruvate kinase deficiency can lead to hemolytic anemia due to reduced ATP production in red blood cells, affecting cell shape and causing phagocytosis.
• Deficiencies in glycolytic enzymes reduce glycolysis rate and ATP production, leading to anemia and red blood cell lysis.

Reference Books

• Biochemistry "Lippincott's Illustrated Reviews", 5th or 6th Edition(Champe, P. C., Harvey, R. A., & Ferrier, D. R., 2005)
• Textbook of biochemistry for medical students, 6th Edition (Vasudevan, D. M., Sreekumari, S., & Kannan, V., 2011)