11.3 Vitamins and Minerals

Fat-soluble versus water-soluble logic

Vitamins are organic cofactors the body cannot make in sufficient amount (niacin from tryptophan and vitamin D from skin are the partial exceptions). Fat-soluble vitamins — A, D, E, K — dissolve in mixed bile-salt micelles, enter enterocytes, and leave in chylomicrons. Anything that steals bile salts or mucosal surface (cholestasis, cystic fibrosis, celiac disease, Crohn disease, chronic orlistat use, pancreatic insufficiency) produces a combined ADEK deficiency pattern. Fat-soluble vitamins are stored in liver and adipose, so deficiency takes months and toxicity is real (especially A and D).

Water-soluble vitamins — the B complex and vitamin C — absorb via specific transporters, are not stored in large depots (vitamin B12 is the exception: hepatic stores last years), and spill into urine. Toxicity is uncommon except pyridoxine sensory neuropathy and niacin flushing / hepatotoxicity at pharmacologic doses. Deficiency can appear in weeks in alcohol-use disorder, dialysis, or a poorly planned vegan diet (B12).

Quick Answer: B1 is TPP (PDH, alpha-KGDH, transketolase). B2 is FAD. B3 is NAD. B5 is CoA. B6 is PLP. Folate is THF. B12 is the only vitamin whose deficiency raises methylmalonic acid. ADEK ride on bile micelles. Give thiamine before glucose in the at-risk patient.

Water-soluble coenzyme map

Vitamin B1 (thiamine) → thiamine pyrophosphate (TPP). TPP is the cofactor for pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, branched-chain ketoacid dehydrogenase, and transketolase (pentose phosphate pathway). Without it, pyruvate and alpha-ketoglutarate pile up, acetyl-CoA from carbohydrate falls, and ATP from oxidative metabolism collapses in brain and heart. Dry beriberi is a symmetric peripheral neuropathy. Wet beriberi is high-output heart failure and edema. Wernicke encephalopathy is the acute triad of confusion, ataxia, and ophthalmoplegia (mammillary bodies); Korsakoff psychosis adds anterograde amnesia and confabulation. Alcohol-use disorder and polished-rice diets are the classic settings. The lab clue is decreased erythrocyte transketolase activity that rises after TPP is added. Give thiamine before a glucose infusion: a glucose load drives PDH and can precipitate Wernicke in a depleted patient.

Vitamin B2 (riboflavin) → FMN and FAD. FAD is the prosthetic group of succinate dehydrogenase (Complex II), acyl-CoA dehydrogenase, and glutathione reductase. Deficiency: cheilosis, angular stomatitis, magenta tongue, corneal vascularization. It rarely travels alone — look for it in malnourished stems with other B vitamins.

Vitamin B3 (niacin, nicotinic acid) → NAD+ and NADP+. NAD+ is the hydride acceptor for most dehydrogenases of glycolysis, the citric acid cycle, and beta-oxidation; NADP+ serves reductive biosynthesis and the pentose phosphate pathway. Humans can convert tryptophan to niacin (roughly 60 mg tryptophan to 1 mg niacin), so Hartnup disease (neutral amino acid transporter) and carcinoid syndrome (tryptophan siphoned to serotonin) cause pellagra. Pellagra is dermatitis, diarrhea, dementia (and death if untreated) — the photosensitive Casal necklace is fair game. Pharmacologic niacin treats dyslipidemia and causes prostaglandin-mediated flushing; aspirin pretreatment is the mechanism-level trick.

Vitamin B5 (pantothenate) → coenzyme A and the acyl-carrier protein of fatty acid synthase. CoA carries acyl groups as thioesters (acetyl-CoA, succinyl-CoA, fatty acyl-CoA). Isolated deficiency is uncommon (dermatitis, enteritis, alopecia) but the cofactor itself is everywhere in Session 2 chemistry.

Vitamin B6 (pyridoxine, pyridoxal, pyridoxamine) → pyridoxal phosphate (PLP). PLP is the cofactor for transaminases (ALT, AST), decarboxylases that make neurotransmitters (glutamate decarboxylase → GABA; DOPA decarboxylase), glycogen phosphorylase, cystathionine beta-synthase, and ALA synthase (heme synthesis). Deficiency: sideroblastic anemia, peripheral neuropathy, seizures (low GABA), cheilosis. Isoniazid forms hydrazones with PLP and produces functional B6 deficiency — always paired on exams. Toxicity: sensory neuropathy at high supplement doses.

Vitamin B7 (biotin) is not always named on every test-plan bullet, but it is the cofactor for the carboxylases: pyruvate carboxylase, acetyl-CoA carboxylase, propionyl-CoA carboxylase, and methylcrotonyl-CoA carboxylase. Avidin in raw egg whites binds biotin. Multiple carboxylase deficiency (holocarboxylase synthetase or biotinidase) presents with lactic acidosis, organic aciduria, and rash.

Vitamin B9 (folate) → tetrahydrofolate (THF). THF carries one-carbon units (methyl, methylene, formyl) for purine carbons and thymidylate synthase. Body stores last months. Deficiency: megaloblastic anemia, hypersegmented neutrophils, neural-tube defects in the embryo, elevated homocysteine, normal methylmalonic acid. Leafy greens; destroyed by overcooking. Methotrexate, trimethoprim, and phenytoin interfere with folate metabolism or absorption.

Vitamin B12 (cobalamin) → methylcobalamin and adenosylcobalamin. Two reactions only, and both are tested:

1. Methionine synthase (methylcobalamin): homocysteine + N5-methyl-THF → methionine + THF. Without B12, folate is trapped as N5-methyl-THF (folate trap), so a B12-deficient marrow looks folate-deficient.
2. Methylmalonyl-CoA mutase (adenosylcobalamin): methylmalonyl-CoA → succinyl-CoA. Without B12, methylmalonic acid rises and odd-chain fatty acids are mishandled — one proposed mechanism of subacute combined degeneration (dorsal columns and corticospinal tracts).

Absorption is a chemistry-plus-anatomy sequence: salivary haptocorrin (R-binder) protects B12 in acid, pancreatic proteases free it, gastric parietal-cell intrinsic factor binds it, terminal ileum cubilin receptors absorb the complex, transcobalamin II carries it in blood. Stores last years, so vegan deficiency and pernicious anemia are slow. Labs: megaloblastic anemia, high homocysteine, high MMA, and neurologic disease that folate will not prevent.

Vitamin C (ascorbate) is a reducing agent. It is required for prolyl and lysyl hydroxylase in collagen synthesis — without hydroxylation, the triple helix is unstable (scurvy: poor wound healing, perifollicular hemorrhage, corkscrew hair, bleeding gums, and mechanically weak ligaments and anulus). It also keeps dietary iron as Fe2+ for DMT1 absorption and regenerates vitamin E. Excess: osmotic diarrhea, oxalate kidney stones, false-negative stool guaiac, and rebound scurvy if megadoses stop abruptly.

Fat-soluble vitamins A, D, E, K

Vitamin A exists as retinol, retinal, and retinoic acid. 11-cis-retinal is the chromophore of rhodopsin; deficiency begins as nyctalopia (night blindness), then Bitot spots, xerophthalmia, and keratinizing metaplasia. Retinoic acid is a nuclear-receptor ligand for epithelial differentiation. Toxicity: teratogenicity (isotretinoin), hepatotoxicity, and idiopathic intracranial hypertension. Measles mortality falls when vitamin A is repleted in deficient children — a public-health fact that still appears as a mechanism (immune epithelial integrity).

Vitamin D is a secosteroid. Skin 7-dehydrocholesterol plus UVB yields cholecalciferol; liver 25-hydroxylase produces the storage form 25-hydroxyvitamin D; kidney 1-alpha-hydroxylase (stimulated by PTH, low phosphate) produces 1,25-dihydroxyvitamin D (calcitriol). Calcitriol induces intestinal TRPV6 calcium channels and calbindin, and it works with PTH on bone. Deficiency: rickets in children, osteomalacia in adults. Toxicity: hypercalcemia, stones, metastatic calcification. Chronic kidney disease loses 1-alpha-hydroxylase; that is a chemistry explanation of renal osteodystrophy, not a nephrology tangent.

Vitamin E (tocopherols) is the membrane lipid-soluble antioxidant, protecting polyunsaturated fatty acids and erythrocyte membranes. Deficiency (fat malabsorption, abetalipoproteinemia): hemolytic anemia, ataxia, and dorsal-column findings that mimic B12 but with normal MMA. High-dose E can antagonize vitamin K and raise bleeding risk on warfarin.

Vitamin K is the cofactor for gamma-glutamyl carboxylase, which carboxylates glutamate residues on factors II, VII, IX, X and proteins C and S, allowing Ca2+ binding to phospholipid. The vitamin K cycle needs epoxide reductase, the target of warfarin. Green leafy vegetables and colonic flora supply K. Newborns have sterile guts and poor placental transfer — hence intramuscular vitamin K at birth. Deficiency: bleeding with elevated PT/INR first (factor VII is shortest-lived). Broad-spectrum antibiotics can drop floral K.

Key minerals: Fe, Ca, Mg, Zn, I, Se

Iron is the metal of heme (hemoglobin, myoglobin, cytochromes of the electron-transport chain, catalase). Nonheme dietary iron is absorbed as Fe2+ via DMT1; vitamin C reduces Fe3+ to Fe2+. Ferroportin exports iron; hepcidin internalizes ferroportin in inflammation and iron overload. Plasma transport is transferrin; storage is ferritin (soluble) and hemosiderin. Deficiency: microcytic hypochromic anemia, high TIBC, low ferritin. Excess: hereditary hemochromatosis (low hepcidin), with free-radical damage via Fenton chemistry.

Calcium is hydroxyapatite, excitation-contraction coupling, neurotransmitter release, and clotting. Serum Ca2+ is defended by PTH, calcitriol, and calcitonin. Chemistry items often pair calcium with vitamin D hydroxylation rather than with bone histology.

Magnesium is the counter-ion of ATP (Mg-ATP is the true substrate of kinases and the Na+/K+-ATPase). Hypomagnesemia impairs PTH secretion and PTH action, so refractory hypocalcemia will not correct until magnesium is replaced. It is also a cofactor for many phosphatases.

Zinc sits in carbonic anhydrase, alcohol dehydrogenase, collagenases, and zinc-finger transcription factors. Deficiency: delayed wound healing, hypogonadism, dysgeusia, diarrhea, and the inherited transporter defect acrodermatitis enteropathica (periorificial and acral rash). For a chiropractic basic-science audience, zinc and vitamin C are the micronutrients most directly tied to connective-tissue repair chemistry.

Iodine is required to iodinate tyrosyl residues on thyroglobulin (thyroid peroxidase, hydrogen peroxide). Deficiency: goiter and, in fetal life, cretinism. Excess can also disturb thyroid economy (Wolff-Chaikoff).

Selenium is inserted as selenocysteine into glutathione peroxidase and deiodinases (T4 to T3). Deficiency: Keshan cardiomyopathy in selenium-poor regions. Toxicity: garlic breath, hair and nail loss.

Food-source memory that is still worth one table: B12 is animal products only; folate is foliage; thiamine is unrefined grains and pork; vitamin C is citrus and peppers; vitamin K and folate share leafy greens; vitamin D is fatty fish, fortification, and sun; iron is heme meat plus legumes with ascorbate; iodine is iodized salt and seafood; zinc is meat and shellfish; selenium tracks soil content of grains.

When a stem gives a cofactor, name the enzyme. When it gives a syndrome, name the cofactor. That two-way map is the entire vitamin game on Part I Chemistry.