Carbohydrate Metabolism Overview

CHO Metabolism

• CHO metabolism involves the fate of food molecules after digestion and absorption.
• It's the chemical enzymatic reactions inside the body, concerned with synthesis and breakdown of substances.

Metabolic Pathways

• Anabolic pathways: Synthesis of complex molecules from simpler ones, requiring energy (e.g., protein synthesis).
• Catabolic pathways: Breakdown of complex molecules into simpler ones, releasing energy (e.g., oxidative processes).
• Amphibolic pathways: Link between anabolic and catabolic pathways (e.g., citric acid cycle).

Carbohydrate Metabolism

• Carbohydrates provide 50% of daily calories.
• Complete oxidation of 1 gram of carbohydrates yields 4 kcal.
• Sources of CHO in food:
  • Starch (about 50%, e.g., potatoes)
  • Sucrose and lactose
  • Fructose and glucose (fruits, honey)

CHO Digestion

• Polysaccharides and disaccharides must be converted to monosaccharides for absorption.
• Enzymes involved:
  • Salivary amylase: Converts starch and glycogen into dextrins.
  • Pancreatic amylase: Converts dextrins into maltose.
  • Intestinal disaccharidases:
    • Maltase: Converts maltose into 2 glucose molecules.
    • Sucrase: Converts sucrose into glucose and fructose.
    • Lactase: Converts lactose into glucose and galactose.

Lactose Intolerance

• Definition: A disease (congenital or acquired), caused by lactase enzyme deficiency.
• Effects: Undigested lactose accumulates in the intestines, leading to bacterial fermentation, producing acids and gases.
• Symptoms: Abdominal distension, cramps, diarrhea.
• Treatment: Lactose-free milk formula.

Metabolic Pathways of Carbohydrates

• Catabolic pathways: Glycolysis, pentose phosphate shunt (Uronic acid), and glycogenolysis.
• Anabolic pathways: Gluconeogenesis and glycogenesis.
• Amphibolic pathways: Citric acid cycle.

Glycolysis

• Definition: Oxidation of glucose to pyruvate (with oxygen) or lactate (without oxygen).
• Major pathway for glucose oxidation.
• Location: Cytoplasm of all tissue cells.
• Importance in specific tissues: Tissues without mitochondria (RBCs, cornea, lens). Tissues with frequent oxygen lack (skeletal muscles).
• Stages:
  • Stage 1: Energy-requiring stage: Converts glucose into glyceraldehyde-3-P (needs energy).
  • Stage 2: Energy-producing stage: Converts glyceraldehyde-3-P to pyruvate or lactate (produces energy).

Importance of Glycolysis

• Energy production: Anaerobic glycolysis (2 ATP), aerobic glycolysis (6-8 ATP).
• Metabolism of fructose and galactose.
• Good oxygenation of tissues: 2,3 biphosphoglycerate decreases Hb's affinity for oxygen.
• Provides important intermediates: (e.g., glycerol-3-P for lipogenesis, pyruvate for alanine amino acid synthesis.)

Energy Production of Glycolysis

• ATP consumption (both aerobic and anaerobic glycolysis): Glucose to G-6-P (1 ATP). Fructose-6-P to fructose 1,6 biphosphate (1 ATP). Net energy consumed = 2 ATP.
• ATP production (Aerobic glycolysis):
  • 4 ATP by substrate level phosphorylation.
  • 4 or 6 ATP from oxidative phosphorylation of 2 NADH+H+ by respiratory chain.
• Net energy gain (Aerobic): 8-10 ATP.
• Net energy gain (Anaerobic): 2 ATP.

Substrate-Level Phosphorylation

• Definition: Phosphorylation of ADP to ATP at the level of the reaction itself, without the respiratory chain.
• Example: 1,3 biphosphoglycerate + ADP → 3 phosphoglycerate + ATP

Glycolysis in Red Blood Cells (RBCs)

• Mature RBCs lack mitochondria, relying entirely on glycolysis for energy.
• Lactate is the end product.
• Net energy yield = 2 ATP.
• Glucose uptake doesn't depend on insulin.
• 2,3 biphosphoglycerate production.

Regulation of Glycolysis

• Key enzymes: Hexokinase/glucokinase, Phosphofructokinase-1 (PFK-1), Pyruvate kinase.
• Hormonal regulation: Insulin stimulates enzyme synthesis, glucagon inhibits.
• Allosteric regulation:
  • G-6-P inhibits hexokinase (not glucokinase)
  • Fructose-2,6-biphosphate stimulates PFK-1 and pyruvate kinase.
  • Citrate inhibits PFK-1.
• Covalent modification: Pyruvate kinase inactivated by phosphorylation.
• Energy regulation: ATP and AMP effects on PFK-1 and pyruvate kinase

In Vitro Inhibition of Glycolysis

• Inhibitors:
  • Arsenate: Competes with inorganic phosphate in Glyceraldehyde-3-P reaction.
  • Iodoacetate: Inhibits Glyceraldehyde-3-P dehydrogenase.
  • Fluoride: Inhibits enolase.
• Clinical relevance: Hemolytic anemia can result from impaired glycolysis (specifically pyruvate kinase deficiency) in RBCs.