Biochemistry Chapter on Carbohydrate Digestion

Metabolism & Bioenergetics Overview

• This topic covers carbohydrate metabolism, glucose metabolism, the citric acid cycle, and oxidative phosphorylation.

Carbohydrate Metabolism Learning Outcomes

• Differentiate various carbohydrate metabolism pathways.

Carbohydrate Metabolism Topics

• Introduction to metabolism
• Digestion, Absorption, and Transport of carbohydrates
  • Different types of digestive enzymes
  • Different types of transport systems in absorption
  • Types of defects and abnormalities in these systems
• Glycolysis
• Gluconeogenesis
• Pentose Phosphate Pathway

Cellulose Digestion

• Cellulose contains β(1-4) bonds between glucose molecules.
• Humans lack the β(1-4) glucosidase to digest these bonds, so cellulose passes through the digestive system.
• Cellulose promotes water retention in the intestine, producing larger, softer feces, and preventing constipation.
• Ruminants and some monogastric animals can digest cellulose with the help of microbial cellulase.

Carbohydrate Absorption

• The end products of carbohydrate digestion (glucose, galactose, and fructose) are absorbed from the jejunum to portal veins and the liver.
• Fructose and galactose are converted to glucose.
• Absorption mechanisms include active transport (against the concentration gradient) and facilitated diffusion.
• Transport proteins are integral membrane proteins facilitating molecule or ion transport across biological membranes.

Mechanisms of Glucose Absorption

• Active transport:

  • Sodium-dependent glucose transporter (SGLT-1) uses energy from the sodium-potassium pump to transport glucose into cells from the intestinal lumen.
  • Sodium is then transported out of the cell against its concentration gradient, maintaining the driving force for glucose transport.
  • Insulin increases glucose transporter numbers in insulin-sensitive tissues.

• Inhibitors of active transport:

  • Ouabain (cardiac glycoside): inhibits adenosine triphosphatase (ATPase), thus affecting the sodium pump.
  • Phlorhizin: inhibits the sodium binding to the carrier protein.

• Passive transport (facilitated diffusion): Utilizes concentration gradient, no energy required.

  • Sodium-independent GLUT transporters (GLUT-2, GLUT-5) facilitate fructose and other monosaccharide transport

• The end products are transported out of the cell into the circulation.

Glucose Transporter Summary

• SGLT-1: Absorption of glucose by active transport (uses Na⁺-K⁺ pump). Located in the intestines and renal tubules.
• GLUT-5: Transports fructose and, to a lesser extent, glucose and galactose. Located in the intestines and sperm.
• GLUT-2: Transports glucose out of intestinal and renal cells to circulation. Located in the intestines, renal tubules, β cells of islets and liver.

Carbohydrate Digestion Defects

• Lactase deficiency (lactose intolerance):
  • Deficiency of lactase, which digests lactose into glucose and galactose
  • Can be congenital or acquired.
  • Results in lactose in the large intestine, where bacteria ferment it causing increased osmotic pressure (water shifts), abdominal cramps, and diarrhea.
• Sucrose deficiency: A rare condition resembling lactase deficiency, affecting the digestion and absorption of sucrose
• Monosaccharide malabsorption: A congenital condition results in slow absorption of glucose and galactose due to a transport defect. Fructose absorption and digestion is unaffected.

Fate of Absorbed Sugars

• Oxidation: Glucose is oxidized via glycolysis and the Krebs cycle to produce energy.
• Storage: Glycogen storage and lipogenesis (fat storage)
• Conversion: Glucose converts to other vital molecules like ribose, deoxyribose, RNA, DNA, glucosamine, galactosamine, mucopolysaccharides, glucoronic acid, and fructose, a compound present in semen.

Glycolysis (Embden-Meyerhof Pathway)

• Breakdown of glucose to pyruvate under aerobic or anaerobic conditions.
• Location: Cytoplasm of all cells.
• Importance in tissues without/poor mitochondria, high oxygen demand tissues like muscles, and cells with no mitochondria like mature RBCs.
• Steps:
  • Energy investment phase (needs energy, 2 ATP consumed)
  • Energy payoff phase (produces ATP and energy, 4 ATP produced).
• Energy production: Net gain of 2 ATP and 2 NADH per glucose molecule.

Anaerobic Respiration (Fermentation)

• Absence of oxygen.
• Lactate fermentation: Occurs in muscle, producing lactate as a by-product.
• Alcohol fermentation: Occurs in yeast and some bacteria, producing ethanol and CO2.

Pyruvate Oxidation

• Pyruvate is converted to Acetyl CoA, which enters the Krebs cycle (aerobic conditions)
• A carboxyl group is removed as CO₂
• An electron pair from the remaining two-carbon fragment is transferred to NAD⁺, forming NADH.
• The resulting acetate combines with coenzyme A (CoA) into acetyl CoA.

Aerobic vs. Anaerobic Glycolysis

• Aerobic glycolysis ends with pyruvate, which enters the mitochondria to produce more ATP in the Krebs cycle and electron transport chain. 
• Anaerobic glycolysis ends with lactate formation, which regenerates NAD+ to sustain glycolysis.

Glucokinase and Hexokinase Comparison

• Glucokinase: Primarily in liver, low affinity for glucose, induced by high blood glucose, doesn't inhibit glucose-6-phosphate.
• Hexokinase: A more general enzyme throughout tissues, high affinity for glucose, inhibited by glucose-6-phosphate.

Key takeaway

• Glycolysis is a fundamental metabolic pathway for energy production in all cells, with different outcomes depending on oxygen availability.