Enzyme Cofactors: The Vitamins & Minerals Enzymes Can't Work Without

Enzymes are the catalysts of biochemistry, but most enzymes can't function alone. They require cofactors — helper molecules that bind to the enzyme and enable its catalytic activity. Most vitamins and many minerals serve primarily as enzyme cofactors, which is why deficiency in these nutrients has such wide-ranging metabolic effects.

Vitamin Cofactors

Nearly every B vitamin functions as an enzyme cofactor: thiamine pyrophosphate (B1), FAD/FMN (B2), NAD+/NADP+ (B3), coenzyme A (B5), PLP (B6), biotin (B7), tetrahydrofolate (B9), and methylcobalamin/adenosylcobalamin (B12). Vitamin C is a cofactor for hydroxylase enzymes (collagen synthesis, carnitine biosynthesis). Vitamin K is a cofactor for gamma-glutamyl carboxylase.

Mineral Cofactors

Zinc is a cofactor for over 300 enzymes. Magnesium is required for over 600 enzymatic reactions and is essential for ATP utilization. Manganese is critical for MnSOD in mitochondria. Selenium is incorporated into selenoenzymes. Copper, iron, and molybdenum all serve as cofactors for specific enzyme families.

The practical takeaway: When an enzyme isn't working well, the issue may not be the enzyme itself but a missing cofactor. This is one reason why broad nutrient sufficiency matters more than any single nutrient — a deficiency in one cofactor can bottleneck an entire metabolic pathway.

For how nutrient combinations affect enzyme function and absorption, see Nutrient Synergies & Antagonisms.

External resources: Linus Pauling Institute — Micronutrient Information Center