Q.21 Which one of the enzymes is responsible for arsenic toxicity?
(A) Pyruvate kinase
(B) Aldolase
(C) Phosphofructokinase
(D) Pyruvate dehydrogenase
Pyruvate dehydrogenase (option D) is the enzyme responsible for arsenic toxicity among the given choices.
Arsenic, particularly arsenite, inhibits this mitochondrial enzyme complex by binding to its lipoic acid cofactor’s dithiol groups, disrupting the conversion of pyruvate to acetyl-CoA and impairing cellular energy production.
This leads to accumulation of pyruvate and lactate, contributing to metabolic acidosis and toxicity symptoms.
Option Analysis
Pyruvate Kinase (A): This glycolytic enzyme catalyzes phosphoenolpyruvate to pyruvate. Arsenic does not specifically target it for toxicity; no direct inhibition links it to arsenic’s primary mechanism.
Aldolase (B): Aldolase cleaves fructose-1,6-bisphosphate in glycolysis. Arsenic shows no notable inhibition of this enzyme in toxicity contexts.
Phosphofructokinase (C): A key regulatory glycolytic enzyme committing glucose to glycolysis. Arsenic affects glycolysis broadly but does not primarily inhibit this enzyme.
Pyruvate Dehydrogenase (D): Correct. Studies on arsenic-exposed rats show significant inhibition of PDH activity, both basal and activated forms, due to direct effects on the enzyme and its regulators.
Pyruvate dehydrogenase stands out as the enzyme responsible for arsenic toxicity, a critical concept in biochemistry for CSIR NET Life Sciences preparation. Arsenic poisoning disrupts energy metabolism by targeting this enzyme.
Arsenic Inhibition Mechanism
Arsenite binds vicinal thiols in PDH’s lipoic acid cofactor, blocking decarboxylation of pyruvate to acetyl-CoA. This halts TCA cycle entry, causing pyruvate buildup and energy crisis.
Studies confirm dose-dependent PDH inhibition in arsenic-fed models, up to 48% basal activity reduction.
Role in Glycolysis and Beyond
PDH links glycolysis to oxidative phosphorylation. Inhibition shifts cells to anaerobic metabolism, mimicking the Warburg effect in toxicity.
Exam Relevance
In MCQs like “which one of the enzymes is responsible for arsenic toxicity,” options like pyruvate kinase or phosphofructokinase mislead as they are glycolytic but not primary targets.
