Each B vitamin operates at a distinct enzymatic node, and their functions are interdependent — deficiency in one impairs the activation and utilization of others.

B1 (Thiamine → TPP): TPP is the obligate cofactor for pyruvate dehydrogenase, which converts pyruvate to acetyl-CoA — the entry point of aerobic glucose oxidation. Without adequate TPP, cells cannot efficiently extract energy from carbohydrates and revert to anaerobic pathways. TPP also drives alpha-ketoglutarate dehydrogenase in the TCA cycle and transketolase in the pentose phosphate pathway.

B2 (Riboflavin → FAD/FMN): FAD and FMN accept electrons at Complex I and Complex II of the mitochondrial electron transport chain, directly participating in ATP synthesis. Riboflavin also activates B6 and folate through FAD-dependent enzymes, and regenerates reduced glutathione via glutathione reductase — linking riboflavin status to cellular antioxidant defense.

B3 (Niacinamide → NAD+/NADP+): NAD+ accepts hydride ions at multiple steps in glycolysis, the TCA cycle, and fatty acid beta-oxidation — making it the most heavily consumed electron carrier in energy metabolism. NAD+ is also the substrate for sirtuin deacetylases (SIRT1–7), which regulate mitochondrial biogenesis, DNA repair, and cellular stress response. NADP+ drives the pentose phosphate pathway and provides reducing equivalents for biosynthesis and cytochrome P450-mediated detoxification. Unlike nicotinic acid, niacinamide does not cause vasodilatory flushing.

B5 (Dexpanthenol → CoA): Coenzyme A is the central metabolic hub linking carbohydrate, fat, and protein metabolism. Acetyl-CoA — the primary CoA thioester — feeds the TCA cycle, ketogenesis, fatty acid synthesis, and cholesterol biosynthesis. CoA is also required for synthesis of acetylcholine and steroid hormones, and for the acetylation of histones that regulate gene expression.

B6 (Pyridoxine → PLP): Pyridoxal-5'-phosphate participates in over 100 enzymatic reactions, more than any other coenzyme. It is the obligate cofactor for transamination (interconversion of amino acids), decarboxylation (synthesis of serotonin from tryptophan, dopamine from DOPA, GABA from glutamate, histamine from histidine), and glycogen phosphorylase (glycogenolysis during fasting or exercise). PLP deficiency produces broad neurological and metabolic dysfunction disproportionate to its apparent simplicity.