Coenzymes

Coenzymes

Coenzymes are small, non-protein organic molecules that are essential for the activity of certain enzymes. They act as carriers of specific chemical groups or electrons between enzymatic reactions. Most coenzymes are derived from B vitamins.

Classification

  • Cosubstrates: Loosely bound, act as second substrate; regenerated by another enzyme. Example: NAD+ (oxidized) ↔ NADH (reduced). Released after each reaction.
  • Prosthetic groups: Tightly (covalently) bound to enzyme; not released. Example: Biotin, FAD in some enzymes.

Major Coenzymes

  • NAD+ / NADH (from Niacin/B3): Electron carriers in catabolism. NAD+ accepts hydride (H⁻) → NADH. Used in glycolysis, TCA cycle, β-oxidation. Reoxidized by ETC Complex I. NADPH (from NADP+) used in reductive synthesis (FA synthesis, steroid synthesis) and antioxidant defense.
  • FAD / FADH₂ (from Riboflavin/B2): Electron carrier. FAD accepts 2 electrons → FADH₂. Tightly bound prosthetic group. Reoxidized by ETC Complex II. Examples: Succinate dehydrogenase (TCA), Acyl-CoA dehydrogenase (β-oxidation).
  • Coenzyme A (CoA-SH) (from Pantothenic acid/B5): Carrier of acyl groups (acetyl-CoA, succinyl-CoA, fatty acyl-CoA). Central to fatty acid metabolism, TCA cycle, cholesterol synthesis. The thioester bond (-CO-S-CoA) is a high-energy bond (activated acyl group).
  • Thiamine Pyrophosphate (TPP) (from Thiamine/B1): Required for oxidative decarboxylation reactions. Key enzymes: Pyruvate dehydrogenase (Pyruvate → Acetyl-CoA), α-Ketoglutarate dehydrogenase (TCA cycle), Transketolase (HMP shunt).
  • Pyridoxal Phosphate (PLP) (from Pyridoxine/B6): Most versatile coenzyme. Involved in ALL amino acid metabolism reactions: Transamination (Aminotransferases), Decarboxylation (decarboxylases), Racemization. Also for glycogen phosphorylase and heme synthesis (ALA synthase).
  • Biotin (B7): Prosthetic group of carboxylases. CO₂ carrier (activated by ATP). Key enzymes: Acetyl-CoA Carboxylase (→Malonyl-CoA, rate-limiting in FA synthesis), Pyruvate Carboxylase (→OAA), Propionyl-CoA Carboxylase.
  • Tetrahydrofolate (THF) (from Folate/B9): Carrier of one-carbon groups (methyl, methylene, formyl, etc.). Essential for: dTMP synthesis (thymidylate synthase), Purine synthesis, Amino acid interconversions (Ser→Gly). Methotrexate → DHF reductase inhibitor → blocks folate metabolism → stops rapidly dividing cells.
  • Cobalamin (B12): Cofactor for: Methionine Synthase (remethylates homocysteine, requires B12 and THF → methyl trap in B12 deficiency) and Methylmalonyl-CoA Mutase (odd-chain fatty acid and amino acid catabolism).
  • Lipoic Acid: Prosthetic group of pyruvate and α-ketoglutarate dehydrogenase complexes. Carries acyl groups and electrons between active sites in multienzyme complex.

Key Clinical Tips

  • TPP, PLP, Biotin, Lipoic acid, FAD are prosthetic groups (tightly bound)
  • NAD+, CoA, THF are cosubstrates (loosely bound, released)
  • Vitamin B12 deficiency → methyl trap (THF trapped as N5-methyl-THF) → folate deficiency symptoms even with adequate folate