Redox biochemistry — In what forms does lipoic acid (lipoamide cofactor) normally exist during catalytic cycling?

Introduction / Context:
Lipoic acid (often as protein-bound lipoamide) is a swinging-arm redox cofactor in multienzyme complexes such as pyruvate dehydrogenase and α-ketoglutarate dehydrogenase. Appreciating its redox cycling explains how acyl-group transfer and electron transfer are coupled.

Given Data / Assumptions:

• Lipoic acid participates in oxidative decarboxylation of α-ketoacids.
• It has a disulfide (S-S) that can be reduced to dithiol (SH, SH).
• Enzymatic cycles involve alternating oxidation states.

Concept / Approach:
During catalysis, lipoamide cycles between an oxidized disulfide and a reduced dithiol. The reduced form accepts acyl groups and transfers reducing equivalents to FAD/NAD+, regenerating the oxidized form for subsequent catalytic rounds. Therefore, it exists in both oxidized and reduced states in vivo.

Step-by-Step Solution:

Verification / Alternative check:
Spectroscopic and structural studies of pyruvate dehydrogenase confirm lipoamide’s redox swing between disulfide and dithiol states with concurrent electron flow.

Why Other Options Are Wrong:

• Only oxidized or only reduced cannot support catalytic cycling.
• “None” contradicts established enzymology.

Common Pitfalls:
Forgetting that lipoamide is covalently tethered to the enzyme and serves both as an acyl carrier and redox carrier, requiring both forms.

Final Answer:
Oxidized and reduced form both