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BCHM503: Advanced Cellular Biochemistry

Overview

  • Date: 3/1/2024
  • Instructor: Sue Fitzmaurice
  • Topics covered:
    • Galactose and Fructose Metabolism
    • HMP Shunt / Pentose Phosphate Pathway
  • Reference Materials: BMB, Chap 22 (440-443), Chap 27 (545-550)

Galactose Metabolism

Key Components
  • Galactose: A monosaccharide part of lactose.
  • Enzymes involved:
    • Lactase: Breaks down lactose into glucose and galactose.
    • Galactokinase: Converts galactose to galactose-1-phosphate (Gal-1-P).
    • Galactose 1-Phosphate Uridyl Transferase: Converts Gal-1-P into glucose-1-phosphate (Glc-1-P).
    • UDP-Galactose-4-Epipmerase: Converts UDP-galactose to UDP-glucose.
Pathway Summary
  • Conversion Process:
    • Galactose -> Galactose-1-P via Galactokinase
    • Galactose-1-P -> UDP-Galactose via galactose 1-P uridyl transferase
    • UDP-Galactose -> UDP-Glucose via epimerase
    • UDP-Glucose -> Glycogen or glycolysis for energy production
Clinical Correlation
Lactase deficiency
  • Symptoms after lactose ingestion include:
    • Diarrhea
    • Bloating
    • Cramps
  • Primary Lactose Intolerance: Hereditary condition, common in Asian and African descent.
  • Secondary Lactose Intolerance: Can develop due to gastrointestinal disturbances such as celiac sprue or colitis.
  • Diagnosis through positive hydrogen breath test.
  • Treatment includes dietary modifications (excluding lactose) or lactase supplements.
Genetic Conditions
Galactokinase Deficiency
  • Autosomal recessive trait
  • Leads to cataracts in early life due to accumulation of galactitol (from galactose).
  • Treatment involves eliminating galactose from the diet.
Galactose-1-Phosphate Uridyltransferase Deficiency (Classic Galactosemia)
  • Symptoms include:
    • Cataracts
    • Vomiting
    • Diarrhea after milk ingestion
    • Liver damage, hyperbilirubinemia
    • Mental impairment over time
  • Early diagnosis and management can lead to normal life expectancy through dietary management.

Fructose Metabolism

Overview
  • Source of fructose includes fruits, sucrose (table sugar), and honey.
  • Fructose metabolism primarily occurs in the liver following absorption.
Metabolic Pathway
  • Conversion Process:
    • Fructose -> Fructose-1-Phosphate (via Fructokinase)
    • Fructose-1-P cleaved by Aldolase B into:
    • Dihydroxyacetone Phosphate (DHAP)
    • Glyceraldehyde
  • Rate of Metabolism: Fructose is metabolized more rapidly than glucose in the liver.
Clinical Correlation
Fructokinase Deficiency
  • Condition is benign, leads to Essential Fructosuria.
Aldolase B Deficiency (Hereditary Fructose Intolerance)
  • Symptoms include:
    • Severe hypoglycemia and lactic acidosis after fructose ingestion
    • Vomiting, lethargy, and diarrhea
    • Liver damage and jaundice
  • Treatment requires dietary restriction of fructose and sucrose.

HMP Shunt/Pentose Phosphate Pathway

Overview
  • Pathway operates parallel to glycolysis, providing NADPH and ribose-5-phosphate.
Key Enzymes and Functions
  • Key Enzymes:
    • Glucose-6-Phosphate Dehydrogenase (G6PDH)
    • Transketolase: Transfers two-carbon units.
  • Functions:
    • Generates NADPH for
    • Fatty acid and cholesterol biosynthesis
    • Antioxidant defenses (maintenance of glutathione levels)
  • Detoxification Reactions: Cytochrome P450 reactions require NADPH.
Clinical Correlation
G6PD Deficiency
  • Common X-linked disorder leading to hemolytic anemia when exposed to oxidative stressors (drugs, fava beans).
  • Symptoms include hemoglobinuria, jaundice, and anemia.
  • Favism: Severe hemolytic reaction after ingestion of fava beans in affected individuals.
  • Management involves avoiding known triggers and monitoring for complications.

Functions of NADPH

  • Key Roles in the Body:
    • Antioxidant defense: Maintains reduced glutathione levels.
    • Essential for detoxification of oxidants.
    • Required in fatty acid and cholesterol synthesis.
  • Sources of NADPH: Notably produced in the liver, contributing to overall metabolic processes.

Conclusion

  • Understanding carbohydrate metabolism (galactose, fructose) and the role of the HMP shunt is crucial in biochemistry, particularly in clinical applications related to metabolic disorders.
  • Ongoing studies continue to elucidate the complexities of these pathways and their implications for human health and disease management.