BCHM503 Study Notes

Advanced Cellular Biochemistry

Overview

  • Course: BCHM503
  • Date: 3/1/2024
  • Instructor: Sue Fitzmaurice (FB/SueFitz50)
  • Themes: Humor in adversity, Metabolism of Galactose & Fructose, HMP Shunt/Pentose Phosphate Pathway
  • Text references: BMB, Chap 22 (440-43), Chap 27 (545-50)

Metabolism of Galactose

  • Galactose: A sugar derived primarily from lactose.
Key Metabolic Pathways
  • Digestive enzymes for carbohydrates:
    • Starch:
    • Enzyme: α-amylase → hydrolyzes starch into maltose and α-dextrins.
    • Maltose:
    • Enzymes: maltase → produces glucose.
    • Lactose:
    • Enzyme: lactase → hydrolyzes into glucose and galactose.
    • Sucrose:
    • Enzymes: sucrase → yields glucose and fructose.
Lactose Metabolism & Symptoms of Lactase Deficiency
  • Lactase breaks down lactose into glucose and galactose.
  • Symptoms of lactase deficiency:
    • Diarrhea
    • Bloating
    • Cramps
  • With lactase deficiency, lactose remains undigested, causing symptoms post-ingestion.
Clinical Correlates
  • Types of Lactose Intolerance:
    • Primary: Hereditary lactase deficiency; common in Asian and African populations.
    • Secondary: Can develop post-gastrointestinal disturbances (e.g. celiac disease).
  • Symptoms include explosive watery diarrhea, vomiting, dehydration due to bacterial fermentation of lactose resulting in small organic acids.
  • Diagnosis via hydrogen breath test post-lactose loading.
  • Treatment involves dietary restriction; unpasteurized yogurt may be tolerated due to active Lactobacillus.
Galactose Metabolism
  1. Galactose → converted into Galactose 1-phosphate via Galactokinase with ATP.
  2. Galactose 1-P is then converted into UDP-galactose via Galactose 1-P Uridyltranferase.
  3. Epimerase catalyzes the conversion between UDP-galactose and UDP-glucose.
  • In the well-fed state, galactose may enter glycogen storage or glycolysis.
  • Administration of galactose during hypoglycemia raises blood glucose.
Genetic Disorders of Galactose Metabolism
  • Galactokinase Deficiency:
    • Results in cataracts during infancy due to accumulation of galactitol.
    • Symptoms include:
    • Cataracts
    • Galactosemia
    • Galactosuria
  • Galactose 1-Phosphate Uridyltransferase Deficiency:
    • Symptoms:
    • Early cataracts
    • Vomiting/diarrhea post-lactose ingestion
    • Lethargy, liver damage, mental retardation
  • Management: Dietary galactose restriction is essential for both deficiencies.

Metabolism of Fructose

  • Fructose: Found in fruits, honey, and dietary table sugar; primarily metabolized in the liver.
  • Pathway:
  1. Fructose is phosphorylated by Fructokinase to yield Fructose 1-phosphate.
  2. Fructose 1-phosphate is cleaved by Aldolase B to produce DHAP and Glyceraldehyde.
  3. Fructose metabolism is energetically rapid, surpassing glucose metabolism.
  4. Other tissues utilize Hexokinase to phosphorylate fructose slowly.
Deficiencies in Fructose Metabolizing Enzymes
  • Fructokinase Deficiency (Essential Fructosuria):
    • Benign condition; fructose in urine without significant symptoms.
  • Aldolase B Deficiency (Hereditary Fructose Intolerance):
    • Results in severe hypoglycemia, liver damage, and potential renal issues resembling Fanconi syndrome.
    • Treatment: elimination of fructose from the diet.

Pentose Phosphate Pathway (PPP) / HMP Shunt

  • Function: Provides NADPH, important for biosynthesis and cellular antioxidant defense; bypasses glycolysis.
  • NADPH Roles:
    • Fatty acid synthesis, cholesterol synthesis, detoxification reactions, and maintaining glutathione.
  • HMP Shunt Components:
  • Oxidative Phase:
    • Converts glucose-6-phosphate to ribulose-5-phosphate, generating 2 NADPH and 1 CO₂.
  • Non-Oxidative Phase:
    • Engages transketolase and transaldolase enzymes to convert ribulose-5-phosphate into ribose-5-phosphate and other sugars required for nucleotide synthesis.
  • Clinical Relevance:
    • NADPH is crucial for maintaining reduced glutathione, aiding in the detoxification of reactive oxygen species (ROS) and combating oxidative stress.

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency

  • G6PD Deficiency: An X-linked recessive disorder with over 400 mutations; leads to hemolytic anemia and risks of chronic granulomatous disease (CGD).
    • Symptoms include episodic hemolysis, pallor, jaundice, and responses to oxidative stress (e.g., infections, drugs, consumption of fava beans).
  • Patients are often resistant to malaria, highlighting a complex interplay between genetic traits and environmental pressures.
  • Management: Avoid oxidative stress triggers, such as certain foods and medications; provides vital knowledge for clinical management of affected individuals.

Conclusion

  • The study of galactose and fructose metabolism, alongside enzymatic deficiencies, emphasizes the close connections between genetic conditions, dietary impacts, and metabolic pathways.
Note
  • Date of notes: 3/1/2024
  • Document compiled for BCHM503 Advanced Cellular Biochemistry class.