Biotin-dependent carboxylases are inhibited by avidin (raw egg white). Which metabolic pathway is MOST critically impaired, leading to the characteristic finding of lactic acidosis and organic aciduria?

• A Acetyl-CoA carboxylase deficiency — blocked fatty acid synthesis, causing hyperlipidemia
• B Pyruvate carboxylase deficiency — blocked conversion of pyruvate to oxaloacetate, impairing gluconeogenesis and TCA cycle anaplerosis, causing pyruvate and lactate accumulation ✓
• C Propionyl-CoA carboxylase deficiency alone causing methylmalonic acidemia
• D Beta-methylcrotonyl-CoA carboxylase deficiency causing isovaleric acidemia

Explanation

The four biotin-dependent carboxylases are: pyruvate carboxylase (PC), acetyl-CoA carboxylase (ACC), propionyl-CoA carboxylase (PCC), and 3-methylcrotonyl-CoA carboxylase (MCC). PC deficiency is most critical for producing lactic acidosis: blocked pyruvate → oxaloacetate means pyruvate accumulates and is shunted to lactate by LDH. OAA shortage impairs TCA cycle (impaired anaplerosis) and gluconeogenesis (OAA → PEP pathway blocked). Multiple carboxylase deficiency (biotinidase or holocarboxylase synthetase deficiency) presents with elevated lactate + propionic acid (PCC block) + 3-methylcrotonyl-glycine (MCC block).

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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