Pyruvate carboxylase, the first enzyme of gluconeogenesis, requires which cofactor and is located in which cellular compartment?
A. Thiamine pyrophosphate as cofactor; located in the cytosol
B. NAD+ as cofactor; located in the cytosol
C. FAD as cofactor; located in the peroxisome
D. Biotin (vitamin B7) as cofactor; located in the mitochondrial matrix
Explanation
Pyruvate Carboxylase: Cofactor and Localization
Key Point
Pyruvate carboxylase is a biotin-dependent carboxylase that catalyzes the first committed step of gluconeogenesis: pyruvate + CO₂ + ATP → oxaloacetate + ADP + Pi.
Cofactor Identity
High-YieldNEET PG
Pyruvate carboxylase requires biotin (vitamin B7) as a covalently bound prosthetic group. Biotin is a carboxyl carrier — it accepts the carboxyl group from bicarbonate (HCO₃⁻) and transfers it to pyruvate.
Mnemonic
"Biotin Carboxylates" — All carboxylase enzymes that add CO₂ to a substrate use biotin as a cofactor. Examples:
Pyruvate carboxylase
Acetyl-CoA carboxylase
Propionyl-CoA carboxylase
3-Methylcrotonyl-CoA carboxylase
Cellular Localization
Key Point
Pyruvate carboxylase is located in the mitochondrial matrix. This is critical because:
1.
Pyruvate enters the mitochondrion via the pyruvate carrier
2.
Oxaloacetate (the product) cannot cross the mitochondrial membrane directly
3.
Oxaloacetate is converted to malate or aspartate for export to the cytosol
The Pyruvate Carboxylase Reaction
Pyruvate+CO2+ATPBiotinOxaloacetate+ADP+Pi
Clinical Pearl
Pyruvate carboxylase deficiency is a rare autosomal recessive disorder causing severe lactic acidosis, hypoglycemia, and neurological damage. Biotin supplementation does not help if the enzyme is genetically absent.
Why Mitochondrial Location Matters
The compartmentalization of pyruvate carboxylase in the mitochondria ensures:
Efficient coupling with the citric acid cycle (both use acetyl-CoA and oxaloacetate)
Prevention of futile cycling with glycolysis
Anaplerotic replenishment of TCA cycle intermediates
Practice similar questions
Sign up free to access AI-powered MCQ practice with detailed explanations and adaptive learning.
