Biochemistry9 min readAI-Generated1 view

Vitamins & Cofactors: The Complete High-Yield Biochemistry Guide

Vitamins and cofactors are responsible for some of the most testable clinical vignettes in medicine: the alcoholic with Wernicke-Korsakoff, the breast-fed infant with scurvy, the patient on INH developing neuropathy. This guide organizes all 13 vitamins and key cofactors by function, deficiency, and toxicity — everything you need for the MCAT and USMLE Step 1.

AI-generated content. This guide was written by MedAI's AI and is intended as a study aid. Always cross-reference with your official course materials, textbooks, and instructor guidance before your exam.

The Two Categories: Fat-Soluble vs. Water-Soluble

Fat-soluble vitamins (A, D, E, K) are stored in fat tissue and the liver, so deficiency develops slowly but toxicity from excess supplementation is a real risk. Water-soluble vitamins (B-complex + C) are not stored significantly, so deficiency develops faster but toxicity is rare (exception: B6 at high doses).

The Fat-Soluble Vitamins Mnemonic

"ADEK" — or "All Dogs Eat Kibble." These are the four fat-soluble vitamins: A (retinol), D (calcitriol), E (tocopherol), K (phylloquinone/menaquinone). They require fat absorption — deficiency in fat malabsorption syndromes (Crohn's, cystic fibrosis, cholestasis).

Fat-Soluble Vitamins

Vitamin	Active Form	Function	Deficiency	Toxicity
A (Retinol)	Retinol, retinoic acid, retinal	Vision (retinal in rhodopsin); epithelial cell differentiation; immune function; retinoic acid = nuclear receptor ligand	Night blindness → xerophthalmia → Bitot's spots → corneal ulcers; follicular hyperkeratosis	Teratogenic (birth defects); pseudotumor cerebri; hepatotoxicity; orange skin (carotenemia from provitamin A — benign)
D (Calciferol)	Calcitriol (1,25-(OH)₂D₃) — made in liver (25-OH) then kidney (1-OH)	Increases intestinal Ca²⁺ and phosphate absorption; promotes bone mineralization; immune modulation	Rickets (children): bowing of legs, craniotabes. Osteomalacia (adults): soft bones, bone pain. Hypocalcemia	Hypercalcemia → calcification of vessels/kidneys; metastatic calcification; nephrolithiasis
E (Tocopherol)	α-Tocopherol	Antioxidant (protects cell membranes from lipid peroxidation); enhances vitamin K antagonism at high doses	Hemolytic anemia in premature newborns; spinocerebellar ataxia; peripheral neuropathy; acanthocytosis	Inhibits platelet aggregation; potentiates anticoagulants → bleeding risk
K (Phylloquinone)	Hydroquinone form activates clotting factors	Cofactor for γ-carboxylation of Glu residues in factors II (prothrombin), VII, IX, X, protein C, S, Z	Bleeding (↑ PT/INR, normal PTT); hemorrhagic disease of newborn (newborns lack gut flora and breast milk has little K)	No known toxicity; warfarin reversal with vitamin K

Water-Soluble Vitamins: The B-Complex

Vitamin	Coenzyme Form	Key Reactions	Deficiency Disease
B1 (Thiamine)	TPP (thiamine pyrophosphate)	Pyruvate dehydrogenase (pyruvate → acetyl-CoA); α-KG dehydrogenase (TCA); Transketolase (pentose phosphate pathway)	Wernicke-Korsakoff (alcoholics): ataxia + ophthalmia + confusion → amnesia/confabulation. Wet beriberi (↑CO cardiomyopathy). Dry beriberi (peripheral neuropathy). Give thiamine BEFORE glucose in alcoholics.
B2 (Riboflavin)	FAD, FMN	Oxidative phosphorylation (ETC Complex I/II); fatty acid oxidation	Angular cheilitis, glossitis, corneal vascularization, dermatitis ("the 2 Cs and a D")
B3 (Niacin)	NAD⁺, NADP⁺	Oxidation/reduction reactions; glycolysis, TCA, ETC; synthesized from Tryptophan (60 mg Trp → 1 mg niacin)	Pellagra: 3Ds — Dermatitis (photosensitive), Diarrhea, Dementia (and death = 4th D). Caused by: niacin-poor diet (corn), Hartnup disease, carcinoid (uses Trp for 5-HT), INH therapy
B5 (Pantothenate)	Coenzyme A	Fatty acid synthesis and β-oxidation; TCA (succinyl-CoA); acetylation reactions (acetyltransferases)	Rare; dermatitis, enteritis, alopecia ("Burning feet syndrome")
B6 (Pyridoxine)	PLP (pyridoxal phosphate)	Transamination (aminotransferases); decarboxylation (synthesis of GABA, serotonin, dopamine, histamine, heme); glycogenolysis (glycogen phosphorylase)	Sideroblastic anemia; peripheral neuropathy; convulsions (↓ GABA). Caused by: INH (isoniazid — INH inactivates B6, give B6 prophylactically); oral contraceptives. Toxicity: sensory neuropathy at megadoses
B7 (Biotin)	Covalently attached to carboxylases	CO₂ carrier in carboxylation reactions: pyruvate carboxylase, acetyl-CoA carboxylase, propionyl-CoA carboxylase	Dermatitis, alopecia, neurological symptoms. Caused by: raw egg white (avidin binds biotin); prolonged antibiotic use
B9 (Folate)	THF (tetrahydrofolate)	One-carbon transfer reactions; dTMP synthesis (thymidine for DNA); purine synthesis	Megaloblastic anemia (macrocytic, hypersegmented neutrophils); neural tube defects (supplement in early pregnancy!). No neurological symptoms (unlike B12).
B12 (Cobalamin)	Methylcobalamin, adenosylcobalamin	Methylmalonyl-CoA mutase (odd-chain FA catabolism); methionine synthase (homocysteine → methionine, requires folate); myelin maintenance	Megaloblastic anemia + SUBACUTE COMBINED DEGENERATION OF SPINAL CORD (dorsal columns + corticospinal tracts). ↑ methylmalonic acid + ↑ homocysteine. Cause: strict vegetarians, pernicious anemia (anti-intrinsic factor antibodies)

B12 vs Folate Deficiency: The Critical Distinction

Both cause megaloblastic anemia with macrocytosis and hypersegmented neutrophils. But ONLY B12 deficiency causes neurological symptoms (subacute combined degeneration). Also, giving folate to a B12-deficient patient corrects the anemia but WORSENS the neurological damage. Always check B12 first in megaloblastic anemia.

Vitamin C (Ascorbic Acid)

Function	Details
Collagen synthesis	Cofactor for hydroxylation of proline and lysine in collagen (prolyl/lysyl hydroxylase) — requires Fe²⁺
Iron absorption	Reduces Fe³⁺ → Fe²⁺ in gut; enhances non-heme iron absorption
Antioxidant	Regenerates vitamin E; scavenges ROS
Immune function	Required for neutrophil activity; wound healing

Deficiency = SCURVY: perifollicular hemorrhages, gum bleeding (gingivitis), "corkscrew" hairs, poor wound healing, joint pain, "woody legs." Caused by diet without fresh fruits/vegetables. Classic exam groups: infants on formula only, elderly with poor diet, alcoholics.

Key Cofactors Beyond Vitamins

Cofactor	Source	Role	Deficiency/Clinical Note
Iron (Fe)	Dietary	Heme synthesis; electron carrier (ETC cytochromes); ribonucleotide reductase	Iron deficiency anemia: microcytic, hypochromic. ↑ TIBC, ↓ ferritin, ↓ serum Fe
Zinc (Zn)	Dietary	Cofactor for >300 enzymes; carbonic anhydrase; alcohol dehydrogenase; DNA polymerase; immune function	Acrodermatitis enteropathica; delayed wound healing; hypogonadism; ageusia/anosmia
Copper (Cu)	Dietary	Cytochrome c oxidase; dopamine β-hydroxylase; ceruloplasmin; SOD	Wilson's disease: copper accumulation; Menkes: X-linked copper transport defect → kinky hair, neurodegeneration
Selenium (Se)	Dietary	Glutathione peroxidase (antioxidant); thyroid deiodinase	Keshan disease (dilated cardiomyopathy in Se-poor regions)
SAM (S-adenosyl methionine)	From methionine	Universal methyl donor in methylation reactions (DNA, histones, norepinephrine, creatine, phospholipids)	Deficiency → hyperhomocysteinemia (cardiovascular risk)