CHO Metabolism and Metabolic Pathways

CHO Metabolism

• Presented by Dr. Yasser Elghobashy, Medical Biochemistry and Molecular Biology
• Focuses on the fate of food molecules after digestion and absorption.

Introduction to Metabolism

• Metabolism encompasses the chemical enzymatic reactions within the body.
• These reactions involve the synthesis and breakdown of various substances.

Metabolic Pathways

• Anabolic pathways: These pathways involve the synthesis of complex molecules from simpler ones. This process requires energy input (endergonic).
  • Example: Synthesis of proteins.
• Catabolic pathways: These pathways involve the breakdown of complex molecules into simpler ones. This process releases energy (exergonic).
  • Example: Oxidative processes releasing energy.
• Amphibolic pathways: These act as a link between anabolic and catabolic pathways.
  • Example: Citric acid cycle

Diagrammatic Representation

• Food molecules undergo digestion and absorption to form simpler molecules.
• The simpler molecules enter the amphibolic pathways.
• Branches lead to anabolic pathways (protein, carbohydrates, lipids and nucleic acids) and catabolic pathways (CO2 and water).

Carbohydrate Metabolism

• Carbohydrates contribute 50% of daily caloric intake.
• Complete oxidation of 1 gram of carbohydrate yields 4 kcal.
• Sources of carbohydrates in food:
  • Starch (e.g., potatoes): approximately 50% of dietary carbohydrates.
  • Sucrose and lactose: significant portion of the rest.
  • Fructose and glucose (fruits, honey): additional sources.

Digestion of Carbohydrates

• Polysaccharides and disaccharides require conversion to monosaccharides for absorption.
• Enzymes involved in the process:
  • Salivary amylase: breaks down starch/glycogen into dextrins.
  • Pancreatic amylase: breaks down dextrins into maltose.
  • Intestinal disaccharidases (maltase, sucrase, lactase) further break down disaccharides into monosaccharides:
    • Maltase: maltose to glucose
    • Sucrase: sucrose to glucose and fructose
    • Lactase: lactose to glucose and galactose

Lactose Intolerance

• Definition: A disease resulting from lactase enzyme deficiency (congenital or acquired).
• Cause: Deficiency of lactase enzyme.
• Effects: Undigested lactose accumulates in the intestine leading to fermentation by intestinal bacteria, producing acids and gases.
• Symptoms: Abdominal distension, cramps, and diarrhea.
• Treatment: Lactose-free milk formula

Metabolic Pathways of Carbohydrates

• Catabolic pathways: involve oxidative pathways;
  • Glycolysis
  • Pentose phosphate shunt (Hexose monophosphate)
  • Uronic acid pathway
  • Glycogenolysis
• Anabolic pathways:
  • Gluconeogenesis
  • Glycogenesis
• Amphibolic pathways:
  • Citric acid cycle

Glycolysis

• Definition: Glucose oxidation to pyruvate (with oxygen) or lactate (without oxygen).
• Site: Cytoplasm of all cells; crucial in cells lacking mitochondria (e.g., red blood cells) and cells with frequent oxygen deficiency (e.g., muscle cells during exercise).
• Stages:
  • Stage 1: Energy-requiring step—glucose conversion to glyceraldehyde-3-phosphate.
  • Stage 2: Energy-producing step—glyceraldehyde-3-phosphate conversion to pyruvate/lactate.

Importance of Glycolysis

• Energy production: Anaerobic - 2 ATP; Aerobic - 6-8 ATP.
• Main pathway: for fructose and galactose metabolism from diet.
• Oxygenation of tissues: through 2,3 biphosphoglycerate (affecting Hb O2 affinity).
• Precursors for other molecules: Dihydroxyacetone phosphate (glycerol-3-P for lipogenesis) and pyruvate (alanine synthesis).

Energy Production in Glycolysis

• ATP consumption: 2 ATP (conversion of glucose to fructose-1,6-bisphosphate).
• ATP production (aerobic): 4 ATP from substrate-level phosphorylation and additional 6-8 ATP from oxidative phosphorylation of NADH.
• ATP production (anaerobic): 2 ATP (from substrate-level phosphorylation only).

Net Energy Gain

• Aerobic glycolysis: 8-10 ATP.
• Anaerobic glycolysis: 2 ATP.

Glycolysis in Red Blood Cells

• Mitochondria absent: RBCs rely entirely on glycolysis.
• End-product: Lactate.
• Net energy: 2 ATP.
• Glucose uptake: Independent of insulin.
• 2,3-biphosphoglycerate production: a crucial metabolic feature.

Regulation of Glycolysis

• Key enzymes (irreversible): Hexokinase/glucokinase; Phosphofructokinase-1; Pyruvate kinase
• Hormonal regulation: Insulin promotes enzyme synthesis, glucagon inhibits.
• Allosteric regulation: G-6-P inhibits hexokinase; fructose-2,6-bisphosphate stimulates phosphofructokinase-1; citrate inhibits phosphofructokinase-1; fructose-2,6-bisphosphate stimulates pyruvate kinase.
• Covalent modification: Pyruvate kinase is inactivated by phosphorylation.
• Energy regulation: ATP and AMP affect PFK-1 and pyruvate kinase.
• Note: Fructose-2,6-bisphosphate is an important allosteric regulator for both glycolysis and gluconeogenesis.

In Vitro Inhibition of Glycolysis

• Arsenate: Inhibits glyceraldehyde-3-phosphate dehydrogenase.
• Iodoacetate: Inhibits glyceraldehyde-3-phosphate dehydrogenase.
• Fluoride: Inhibits enolase.

Important Note

• Hemolytic anemia can occur due to pyruvate kinase deficiency. This deficiency negatively affects RBC glycolysis