22.3 Vitamins & Minerals

Vitamins & Minerals

Vitamins are organic micronutrients required in small amounts because humans cannot synthesize them. They are divided into fat-soluble (A, D, E, K) — absorbed with dietary lipid via micelles, stored in liver and adipose, and prone to toxicity in excess — and water-soluble (B complex, C) — absorbed directly, poorly stored, and excess excreted in urine, so deficiency develops faster and toxicity is rare. Minerals are inorganic elements serving structural, enzymatic, and electrolyte roles. The PA-CAT Bulletin of Information, rev. 20240815 lists vitamins and minerals among Biochemistry topics; candidates should pair each micronutrient with its biochemical function and its classical deficiency syndrome.

Fat-Soluble Vitamins

Vitamin A (retinol, retinal, retinoic acid) supports vision and epithelial integrity. Retinal is the 11-cis chromophore of rhodopsin in rod photoreceptors; light isomerizes it to all-trans, triggering the visual cascade. Retinoic acid binds nuclear retinoic acid receptors (RAR/RXR) regulating gene expression in epithelial differentiation. Deficiency causes night blindness (nyctalopia), xerophthalmia, Bitot spots, and follicular hyperkeratosis. Excess causes alopecia, hepatosplenomegaly, and teratogenicity (isotretinoin contraception rule).

Vitamin D (D3 cholecalciferol from skin 7-dehydrocholesterol + UV; D2 ergocalciferol from plants) is hydroxylated in the liver at C-25 (25-hydroxyvitamin D, the storage form measured clinically) and in the kidney at C-1 by 1α-hydroxylase to 1,25-dihydroxycholecalciferol (calcitriol), the active hormone. PTH stimulates 1α-hydroxylase; phosphate and FGF23 inhibit it. Calcitriol increases intestinal Ca2+ and phosphate absorption, and with PTH mobilizes bone. Deficiency causes rickets in children (bowing of long bones, rachitic rosary, widened epiphyses) and osteomalacia in adults (bone pain, fractures). Toxicity causes hypercalcemia, nephrocalcinosis.

Vitamin E (tocopherols, tocotrienols) is the chief lipid-soluble antioxidant in membranes, donating a hydrogen to scavenge lipid peroxyl radicals and interrupt lipid peroxidation. Deficiency is rare but seen in fat malabsorption (cystic fibrosis, abetalipoproteinemia) and causes hemolytic anemia (red cells are vulnerable to oxidative damage), acanthocytosis, ataxia, and retinopathy.

Vitamin K (phylloquinone K1 from plants; menaquinone K2 from bacteria) is the cofactor for γ-glutamyl carboxylase, which carboxylates glutamate residues on clotting factors II, VII, IX, X and proteins C and S, enabling Ca2+ binding and activity. Deficiency causes neonatal hemorrhage (hence vitamin K injection at birth) and bleeding in fat malabsorption or with warfarin, which inhibits vitamin K epoxide reductase. Broad-spectrum antibiotics can precipitate deficiency by killing gut flora.

Water-Soluble Vitamins: B Complex

Thiamine (B1) is a cofactor for pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and transketolase (pentose phosphate pathway). Deficiency causes beriberi (wet: high-output heart failure, edema; dry: peripheral neuropathy) and Wernicke-Korsakoff syndrome (ataxia, nystagmus, ophthalmoplegia, confabulation), classically in alcohol use disorder.

Riboflavin (B2) forms FAD and FMN. Deficiency causes angular stomatitis, glossitis, cheilosis, and corneal vascularization.

Niacin (B3) forms NAD and NADP. Deficiency causes pellagra — the classic 3 Ds: dermatitis (Casal necklace), diarrhea, dementia, progressing to death. Niacin can be synthesized from tryptophan, so pellagra also accompanies Hartnup disease and carcinoid syndrome. High-dose niacin treats dyslipidemia (lowers LDL, raises HDL) but causes flushing blocked by aspirin.

Pantothenic acid (B5) forms coenzyme A. Deficiency is rare; causes burning feet syndrome.

Pyridoxine (B6) forms PLP, a cofactor for transamination, glycogen phosphorylase, cystathionine β-synthase, and heme synthesis (ALA synthase step in some texts). Deficiency causes microcytic anemia, cheilosis, convulsions (notably in infants), and peripheral neuropathy; it is the counter-isomer antagonist in isoniazid therapy.

Biotin (B7) is the cofactor for carboxylases (pyruvate carboxylase, acetyl-CoA carboxylase, propionyl-CoA carboxylase). Deficiency is rare but caused by raw egg white (avidin binds biotin) or parenteral nutrition without biotin; causes dermatitis, alopecia, and metabolic acidosis.

Folate (B9) donates one-carbon units for thymidylate and purine synthesis and for the methylation cycle. Deficiency causes megaloblastic anemia (ineffective erythropoiesis, hypersegmented neutrophils) but — unlike B12 — does NOT cause neurologic deficits. Folate deficiency in early pregnancy causes neural tube defects; supplementation (400 µg/day) is recommended preconception.

Cobalamin (B12) is required to regenerate tetrahydrofolate (methyl-THF → THF via methionine synthase) and for the methylmalonyl-CoA mutase reaction (odd-chain fatty acid metabolism). Deficiency causes megaloblastic anemia PLUS subacute combined degeneration of the spinal cord (demyelination of dorsal and lateral columns → paresthesias, loss of vibration/proprioception, spasticity). Dietary B12 requires intrinsic factor from gastric parietal cells for ileal absorption; pernicious anemia (autoimmune anti-parietal cell or anti-intrinsic factor) is the classic cause.

Vitamin C (ascorbic acid) is a cofactor for prolyl and lysyl hydroxylases in collagen synthesis and for dopamine β-hydroxylase. It is a water-soluble antioxidant and enhances non-heme iron absorption. Deficiency causes scurvy — bleeding gums, petechiae, poor wound healing, corkscrew hairs, perifollicular hemorrhage — because collagen is under-hydroxylated and weak.

Minerals

Calcium (99% in bone) is regulated by PTH (raises serum Ca2+, lowers phosphate), calcitonin (lowers serum Ca2+), and vitamin D (raises both) at gut, kidney, and bone. Ionized Ca2+ drives muscle contraction, neurotransmitter release, and second-messenger signaling. Hypocalcemia causes tetany, Chvostek and Trousseau signs; hypercalcemia causes stones, bones, abdominal groans, and psychic moans.

Iron is absorbed in the duodenum as Fe2+ (ascorbate reduces Fe3+); ferroxidase/hephaestin oxidizes it to Fe3+ for transferrin transport; it is stored as ferritin (soluble, available) and hemosiderin (insoluble). Iron is the center of heme and of iron-sulfur clusters in the electron transport chain (Complexes I, II, III). Deficiency causes microcytic hypochromic anemia; overload (hereditary hemochromatosis, transfusions) damages liver, heart, and pancreas.

Zinc is a cofactor for over 300 enzymes (carbonic anhydrase, alcohol dehydrogenase, superoxide dismutase, matrix metalloproteinases) and zinc-finger transcription factors. Deficiency causes growth retardation, hypogonadism, impaired wound healing, acrodermatitis enteropathica (rare autosomal recessive transporter defect), and anosmia.

Magnesium is required for ATP utilization (Mg-ATP is the active substrate), kinase activity, neuromuscular function, and parathyroid hormone release. Hypomagnesemia causes muscle cramps, seizures, arrhythmias, and refractory hypocalcemia (impairs PTH secretion and action).

Iodine is incorporated into T3 and T4. Deficiency causes goiter and, in fetal/early life, cretinism (intellectual disability, deaf-mutism, motor rigidity). The WHO salt-iodization program addresses endemic iodine deficiency.

Selenium is a component of glutathione peroxidase (hydrogen peroxide detoxification) and deiodinases (T4 → T3 conversion). Deficiency (seen in parts of China with selenium-poor soil) causes Keshan disease (cardiomyopathy) and Kashin-Beck disease (osteoarthropathy).