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.