Vitamin & mineral lookup

Three forms, three non-interchangeable jobs — and the last oxidation is a one-way door.

What it does

• Retinal — the vision form. 11-cis-retinal binds opsin to make RHODOPSIN in rods.
• Retinoic acid — binds the nuclear retinoic acid receptor (RAR), which binds DNA response elements and controls retinoid-dependent genes such as keratin. Maintains epithelial differentiation and mucus secretion.
• Retinol and retinal — reproduction: spermatogenesis in males, prevention of fetal resorption in females.
• β-carotene is the plant provitamin, cleaved in the intestine to TWO retinals; conversion is inefficient in humans.

Deficiency — Night blindness → xerophthalmia

• Night blindness (nyctalopia) — the EARLIEST symptom.
• Prolonged deficiency → irreversible loss of visual cells.
• Xerophthalmia — dryness of conjunctiva and cornea → corneal ulcers → opaque scarring → blindness.
• Impaired epithelial differentiation → mucosal barrier failure → more infections.

Toxicity

Hypervitaminosis A — from PREFORMED vitamin A (retinoids), not β-carotene. Dry pruritic skin, hepatomegaly, and TERATOGENICITY: isotretinoin is contraindicated in women of childbearing potential.

Pearls

• Retinal → retinoic acid is IRREVERSIBLE, so retinoic acid can neither support vision nor act as a storage form.
• Stored in the liver as retinyl esters; released bound to retinol-binding protein (RBP) complexed with transthyretin (TTR), which protects it from renal filtration.
• The visual cycle: 11-cis-retinal + opsin → rhodopsin; light isomerises it to all-trans-retinal (bleaching); that activates TRANSDUCIN → nerve impulse; all-trans is converted back to 11-cis, partly in the retinal pigment epithelium.

"Retinol is vitamin A — think Retin-A for wrinkles and acne."

FMK-09.1 slides 8–12

A vitamin that behaves like a hormone: two hydroxylations, and only the second one is regulated.

What it does

• Skin makes cholecalciferol (D₃) from 7-dehydrocholesterol under UV light; diet supplies D₃ (animal) and D₂/ergocalciferol (plants, fortified food).
• LIVER 25-hydroxylation → calcidiol (25-OH-D), the predominant circulating form.
• KIDNEY 1α-hydroxylation → calcitriol, the active form. Stimulated by PTH and low phosphate — the only tightly hormonally controlled step.
• Intestine: calcitriol raises absorption of both calcium and phosphate. Bone: with PTH, promotes osteoclast-mediated resorption. Together they supply the Ca and Pi for hydroxyapatite, Ca₅(PO₄)₃OH.

Deficiency — Rickets (children) / osteomalacia (adults)

• Rickets — growth continues, collagen matrix is laid down but incompletely mineralised → soft, deformed bones (bowed legs).
• Osteomalacia — demineralisation of PRE-EXISTING bone → fractures.

Toxicity

Hypervitaminosis D — enhanced intestinal calcium absorption → HYPERCALCEMIA → metastatic deposition of calcium salts in soft tissue.

Pearls

• Order CALCIDIOL (25-OH-D) to assess status — longer half-life, reflects both diet and sun. Calcitriol is NOT the screening test: its tight regulation can mask a deficiency of the storage form.
• The phosphate discriminator: vitamin D deficiency gives LOW phosphate. Hypoparathyroidism gives HIGH phosphate with low calcium — opposite direction of phosphate change.
• PTH raises renal calcium reabsorption and calcitriol synthesis while LOWERING phosphate reabsorption (phosphaturic).

FMK-09.1 slides 14–16

The membrane's antioxidant bodyguard — and a deficiency that is almost never dietary.

What it does

• Lipid-soluble antioxidant: prevents non-enzymatic peroxidation of polyunsaturated fatty acids (PUFAs) in membranes and lipoproteins.
• Specifically protects membrane PUFAs and LDL particles from oxidation — both contributors to membrane damage and vascular injury.
• Requirement RISES with dietary PUFA intake — more oxidisable substrate needs more protection.

Deficiency — Hemolytic anemia + neurologic findings

• Hemolytic anemia from fragile RBC membranes, especially in premature infants.
• Neurologic: spinocerebellar ataxia, loss of deep tendon reflexes, peripheral neuropathy — oxidative damage to long, lipid-rich axons over time.

Toxicity

Uncommon and generally mild — a relatively wide safety margin compared with A and D.

Pearls

• In adults, deficiency is almost always defective lipid ABSORPTION or TRANSPORT, not low intake.
• ABETALIPOPROTEINEMIA — defective chylomicron and VLDL formation — impairs fat-soluble vitamin delivery, vitamin E in particular.
• Newborns depend on breast milk or formula: placental transfer of vitamin E is limited.

FMK-09.1 slides 22–23

K is for Koagulation — and for the enzyme warfarin blocks.

What it does

• Cofactor for γ-GLUTAMYL CARBOXYLASE, which carboxylates specific glutamate residues to γ-carboxyglutamate (Gla) on clotting proteins made in the liver.
• Gla residues are strong chelators of Ca²⁺. The prothrombin–calcium complex binds negatively charged phospholipids exposed on damaged endothelium and activated platelets — concentrating the cascade exactly at the injury.
• Vitamin K-dependent factors: II (prothrombin), VII, IX, X, plus regulatory proteins C and S.
• THE CYCLE: the reduced hydroquinone is the active cofactor and is oxidised to vitamin K EPOXIDE during carboxylation; VKOR (epoxide reductase) regenerates it, so a small pool is reused many times.

Deficiency — Bleeding — hypoprothrombinemia

• True dietary deficiency is rare in healthy adults — vitamin K is widespread and gut bacteria make menaquinone.
• Seen with malabsorption, or after prolonged antibiotics that disrupt gut flora.
• HEMORRHAGIC DISEASE OF THE NEWBORN — neonates have low stores and sterile guts; a single IM dose at birth is standard prophylaxis.

Pearls

• WARFARIN inhibits VKOR. It does not destroy existing factors — it prevents synthesis of new functional ones, which is why the effect takes several days.
• Monitored with PT/INR — the extrinsic pathway, reflecting factor VII, which has the shortest half-life of the vitamin K-dependent factors.
• Certain CEPHALOSPORINS cause hypoprothrombinemia by inhibiting VKOR directly — the same enzyme.
• Contrast heparin: activates antithrombin III, a different and immediate mechanism; the two are bridged clinically.
• Forms: K1 phylloquinone (plants), K2 menaquinone (gut bacteria), menadione (synthetic).

"K is for Koagulation."

FMK-09.1 slides 18–20

Four dehydrogenases, and the reason you give thiamine before glucose.

What it does

• TPP is required by four enzymes — Branched-chain α-ketoacid dehydrogenase, α-Ketoglutarate dehydrogenase, Pyruvate dehydrogenase, and Transketolase.
• Because TPP sits at the gateway from glycolysis into the TCA cycle (PDH), deficiency starves the most aerobic, glucose-dependent tissues first: BRAIN and HEART.

Deficiency — Beriberi · Wernicke–Korsakoff

• DRY beriberi — peripheral neuropathy, especially the legs.
• WET beriberi — high-output cardiac failure from dilated cardiomyopathy, with edema.
• WERNICKE encephalopathy (acute, reversible if treated): confusion, ophthalmoplegia, gait ataxia.
• KORSAKOFF psychosis (chronic, often irreversible): confabulation, anterograde and retrograde memory impairment. Classically alcohol use disorder.

Pearls

• THE DEXTROSE TRAP — giving IV glucose to a thiamine-deficient patient consumes the remaining TPP and can acutely precipitate or worsen Wernicke encephalopathy. Give THIAMINE BEFORE OR WITH glucose in anyone at risk.

"Be APT" — BCKA dehydrogenase, α-Ketoglutarate dehydrogenase, PDH, Transketolase."Ber1Ber1" — beriberi is B1.

Acts here

PDH — glycolysis into the TCA cycle →α-KG dehydrogenase in the TCA cycle →Transketolase in the HMP shunt →

FMK-09.2 slides 8–9

Two flavin cofactors, two C's for the deficiency.

What it does

• FAD (flavin adenine dinucleotide) and FMN (flavin mononucleotide) both derive from riboflavin.
• Each accepts two hydrogens to become FADH₂ / FMNH₂ — tightly bound, prosthetic-group-like cofactors for flavoenzymes.
• Classic examples: NADH dehydrogenase (ETC Complex I, uses FMN) and succinate dehydrogenase (Complex II / TCA, uses FAD).

Deficiency — Cheilosis and corneal vascularization

• Cheilosis — inflammation and cracking at the corners of the mouth and lips.
• Corneal vascularization.
• Uncommon in isolation; usually accompanies other B-vitamin deficiencies in malnourished patients.

Pearls

• Riboflavin is LIGHT-SENSITIVE — phototherapy for neonatal hyperbilirubinemia can degrade it and sometimes requires supplementation.

"The 2 C's of B2" — Cheilosis and Corneal vascularization.FAD and FMN come from riboFlavin.

Acts here

Complex I uses FMN →Complex II uses FAD →FAD in β-oxidation →

FMK-09.2 slide 10

The redox currency — and a vitamin that doubles as a lipid drug.

What it does

• NAD⁺ and its phosphorylated derivative NADP⁺ are the active coenzymes, both from niacin.
• Coenzymes in oxidation–reduction reactions, accepting a hydride to become NADH and NADPH.
• The cellular NAD⁺/NADH ratio reports the overall redox state of the cell.

Deficiency — Pellagra — the 3 D's

• Dermatitis (photosensitive), Diarrhea, Dementia — untreated, progresses to Death.
• HARTNUP DISEASE — defective neutral amino acid transporter in gut and kidney impairs tryptophan uptake → less substrate for endogenous niacin synthesis → pellagra-like picture. "Niacin deficiency without a niacin-poor diet."

Pearls

• At about 100× the RDA, niacin inhibits adipocyte lipolysis → fewer circulating free fatty acids → less hepatic VLDL/TAG production → lowers LDL. Used in type IIb hyperlipoproteinemia.

Pellagra = the 3 D's (Dermatitis, Diarrhea, Dementia) → Death.

Acts here

NAD⁺ at PDH →NAD(P)⁺ at GDH →NAD⁺ in β-oxidation →

FMK-09.2 slide 11

Everywhere an acyl group needs carrying — and no human deficiency syndrome.

What it does

• A structural component of Coenzyme A.
• CoA's thiol (–SH) group carries acyl groups: succinyl-CoA, fatty acyl-CoA, acetyl-CoA.
• Also the acyl-carrier-protein domain of fatty acid synthase.

Deficiency — None reported in humans

• No deficiency syndrome has been reported — pantothenic acid is abundant in nearly all foods.

Acts here

CoA at PDH →ACP domain of fatty acid synthase →

FMK-09.2 slide 12

The amino-acid vitamin — and the only water-soluble one with a real toxicity syndrome.

What it does

• TRANSAMINATION (ALT, AST) — the core of amino acid nitrogen handling.
• DECARBOXYLATIONS, e.g. histamine synthesis.
• Synthesis of glutathione, cystathionine, HEME, niacin, and the neurotransmitters serotonin, dopamine, norepinephrine, epinephrine and GABA.
• Also required by GLYCOGEN PHOSPHORYLASE — the one place PLP is not doing amino acid chemistry.

Deficiency — Convulsions, neuropathy, sideroblastic anemia

• Convulsions and hyperirritability.
• Peripheral neuropathy.
• SIDEROBLASTIC ANEMIA — impaired hemoglobin synthesis with iron excess.

Toxicity

The ONLY water-soluble vitamin with a well-documented toxicity: SENSORY NEUROPATHY from megadosing, which may NOT fully resolve after stopping.

Pearls

• Deficiency is rare but DRUG-INDUCED is the classic route: isoniazid and chloramphenicol form an inactive PLP derivative.
• The sideroblastic anemia mechanism: PLP runs ALA SYNTHASE, the first step of heme synthesis. Without it, heme synthesis stalls despite normal or increased iron delivery, so iron piles up in the mitochondria of erythroid precursors — RINGED SIDEROBLASTS, iron-laden mitochondria encircling the nucleus.
• Sideroblastic anemia causes: congenital (X-linked ALAS2 mutations) or acquired — isoniazid, chronic alcohol use, lead toxicity.

Acts here

ALA synthase — the sideroblastic anemia link →CBS — transsulfuration →Cystathionase — the second B6 step →Transamination →DOPA decarboxylase → dopamine →The same AADC → serotonin →Tyrosine degradation →Glycogen phosphorylase — the odd one out →

FMK-09.2 slides 14–15

One job, done by carboxylases — and one bizarre way to become deficient.

What it does

• Coenzyme for CARBOXYLATION — carries activated CO₂, a one-carbon transfer.
• PYRUVATE CARBOXYLASE: pyruvate (3C) → oxaloacetate (4C) — anaplerotic and gluconeogenic.
• ACETYL-CoA CARBOXYLASE: acetyl-CoA (2C) → malonyl-CoA (3C) — the first committed step of fatty acid synthesis.
• PROPIONYL-CoA CARBOXYLASE — on the route from α-ketobutyrate to succinyl-CoA.

Deficiency — Rare

• Readily available in the diet and made by gut bacteria, so deficiency is rare.
• THE EXCEPTION: raw egg white contains AVIDIN, a glycoprotein that binds biotin so tightly it blocks absorption. Excessive raw egg white intake can induce deficiency.

"AVIDin in egg white AVIDly binds biotin."

Acts here

Pyruvate carboxylase — gluconeogenesis →ACC — committed step of fatty acid synthesis →Propionyl-CoA carboxylase →

FMK-09.2 slide 12

One-carbon units for DNA — the vitamin whose deficiency shows up where cells divide fastest.

What it does

• THF, the reduced form, is the active coenzyme.
• Receives a one-carbon fragment from a donor (serine, glycine, histidine) and hands it to the synthesis of amino acids, PURINE nucleotides, and THYMIDINE monophosphate.
• Because purine and TMP synthesis both depend on THF, folate status directly controls how fast cells can make new DNA — the thread connecting folate to marrow, gut mucosa and the developing fetus.

Deficiency — Megaloblastic anemia · neural tube defects

• The MOST COMMON vitamin deficiency in the US, particularly in pregnant women.
• Macrocytic/megaloblastic anemia — reduced purine and TMP synthesis → impaired DNA synthesis → cells cannot divide on schedule but keep growing → large immature precursors (megaloblasts).
• NEURAL TUBE DEFECTS — spina bifida and anencephaly. Folate closes the neural tube in the first few weeks, so supplementation must start BEFORE conception; damage present at birth is usually permanent.
• Common causes: increased demand (pregnancy, lactation), poor absorption, and METHOTREXATE (a DHFR inhibitor).

Pearls

• Stored in the liver for only 3–4 MONTHS — deficiency develops much faster than B12's.
• Both folate and B12 deficiency raise homocysteine. ONLY B12 also raises methylmalonic acid.
• Folate deficiency does NOT cause neurologic symptoms; B12 deficiency does.

Acts here

Two ring-closure steps in purine synthesis →Thymidylate synthase → dTMP →The folate trap →

FMK-09.2 slides 16–17

Exactly two reactions in the whole body — and both are testable.

What it does

• REACTION 1 — remethylation of homocysteine to methionine (methylcobalamin-dependent).
• REACTION 2 — isomerisation of methylmalonyl-CoA (from odd-chain fatty acids and several amino acids) to succinyl-CoA (5′-deoxyadenosylcobalamin-dependent).
• B12 has a CORRIN ring, structurally similar to the porphyrin ring of heme. Commercial preparation: cyanocobalamin.

Deficiency — Megaloblastic anemia WITH neurologic signs

• Megaloblastic anemia — identical to folate's, via the folate trap.
• NEUROLOGIC symptoms that folate deficiency does not cause: peripheral neuropathy, subacute combined degeneration. This is the distinguishing feature.
• PERNICIOUS ANEMIA — autoimmune destruction of gastric parietal cells → loss of intrinsic factor → severe malabsorption.
• Also after partial/total gastrectomy (loss of IF-producing tissue) or ileal disease/resection (loss of the absorption site).

Pearls

• THE FOLATE TRAP — the remethylation reaction is the ONLY way to regenerate usable THF from N⁵-methyl-THF. Without B12 folate is trapped in that form and cannot serve purine or TMP synthesis, so B12 deficiency produces the SAME megaloblastic anemia as folate deficiency even with normal folate intake.
• THE DISCRIMINATOR — either deficiency raises homocysteine; only B12 deficiency also raises METHYLMALONIC ACID.
• Absorption chain: released from food in the stomach → binds R-protein → freed by pancreatic enzymes → binds INTRINSIC FACTOR from parietal cells → IF-B12 binds ileal receptors → absorbed → carried on transcobalamin → liver.
• Made only by microorganisms — NOT present in plant foods. Stored in the liver for 3–4 YEARS, so deficiency can take years to appear.

Acts here

Reaction 1 — methionine synthase →Reaction 2 — methylmalonyl-CoA mutase →The folate trap, from the folate side →

FMK-09.2 slides 18–19

Keeps iron reduced — which is why its deficiency is a collagen disease with an anemia attached.

What it does

• Reducing agent and coenzyme in HYDROXYLATION reactions — prolyl and lysyl hydroxylation during collagen synthesis — by keeping the iron in the hydroxylases in its reduced, active state.
• Maintains connective tissue structure and supports wound healing.
• Assists absorption of dietary NON-HEME iron by reducing Fe³⁺ to Fe²⁺, the form intestinal transporters take up.

Deficiency — Scurvy

• Sore, spongy gums; fragile blood vessels; hemorrhage; swollen joints — all from defective collagen hydroxylation.
• MICROCYTIC ANEMIA — secondary to decreased absorption of dietary iron.

Pearls

• Also the reductant for DOPAMINE β-MONOOXYGENASE, which makes norepinephrine from dopamine — one of the few testable vitamin C requirements outside collagen.

"sCurvy" = Collagen synthesis defect.

Acts here

Dopamine → norepinephrine →Tyrosine degradation →

FMK-09.2 slide 20

98% of it is bone; the rest runs signalling, contraction and clotting.

What it does

• ~98% of body calcium sits in bone as HYDROXYAPATITE with phosphorus; the Ca²⁺/Pi ratio (~2:1) matters for mineralisation.
• Signal transduction, muscle contraction, blood clotting.
• Binds and alters the activity of calmodulin, phospholipase A2 and protein kinase C.

Deficiency — Hypocalcemia / hypercalcemia

• HYPERcalcemia — overproduction of PTH; constipation and kidney stones.
• HYPOcalcemia — deficiency of PTH or of vitamin D.

Pearls

• See vitamin D for how calcitriol and PTH move calcium and phosphate in opposite directions.

FMK-09.2 slide 22

Structural in bone and nucleic acids, regulatory everywhere else.

What it does

• ~85% of body phosphorus is in bone as hydroxyapatite.
• A component of phospholipids, nucleic acids, ATP and creatine phosphate.
• Adding and removing phosphate (kinases and phosphatases) regulates enzyme activity directly.

Deficiency — Hypophosphatemia / hyperphosphatemia

• HYPERphosphatemia — decreased PTH. Excess free phosphate binds Ca²⁺ and deposits as crystals in soft tissue.
• HYPOphosphatemia — overuse of ALUMINIUM-containing antacids, which bind phosphate in the gut.

Pearls

• The phosphate direction is the discriminator: vitamin D deficiency lowers phosphate, hypoparathyroidism raises it.

FMK-09.2 slide 22

Water balance, osmotic equilibrium, and the pressure consequences.

What it does

• With potassium, maintain water balance, osmotic equilibrium, acid–base balance and membrane potential.
• Sodium drives Na⁺-linked absorption of glucose, galactose and free amino acids in the gut.
• Chloride is needed for HCl production in the stomach.
• Rising Na⁺ stimulates thirst and ADH release → water retention → higher blood volume → can drive HYPERTENSION.

Deficiency — Hyper-/hyponatremia

• Hypernatremia — from excess water loss.
• Hyponatremia — from decreased ability to excrete water.

FMK-09.2 slide 23

A narrow range, policed by the Na⁺/K⁺-ATPase, with arrhythmia at both ends.

What it does

• Primarily INTRACELLULAR; the steep gradient is maintained by the Na⁺/K⁺-ATPase.
• Essential to membrane potential in neurons and myocytes.

Deficiency — Hyper-/hypokalemia

• The normal serum range is NARROW, and BOTH hyper- and hypokalemia cause cardiac arrhythmias and skeletal muscle weakness.

FMK-09.2 slide 23

Chaperoned at every step, because free iron makes radicals.

What it does

• A component of catalytic proteins (hydroxylases) and noncatalytic ones — electron transport chain carriers, and the heme prosthetic group.
• Free iron is TOXIC: it catalyses reactive oxygen species, so the body binds it at every step.
• Absorbed as Fe²⁺ (ferrous); stored on FERRITIN and transported on TRANSFERRIN, both as Fe³⁺ (ferric).
• Ferritin normally runs about ⅓ saturated — a buffer reserve.

Deficiency — Microcytic anemia / iron overload

• DEFICIENCY → decreased hemoglobin synthesis → MICROCYTIC anemia. Causes: chronic blood loss, poor intake, malabsorption, increased demand (pregnancy, growth).
• OVERLOAD — HEREDITARY HEMOCHROMATOSIS: an HFE mutation leaves hepcidin inappropriately LOW → unchecked absorption → accumulation in liver, pancreas and heart.
• The classic triad: hyperpigmentation + hyperglycemia ("bronze diabetes") + cirrhosis.

Pearls

• FERROPORTIN is the enterocyte iron-export channel; HEPCIDIN, a hepatic peptide hormone, triggers its internalisation and lysosomal degradation, blocking iron release into blood.
• Hepcidin is SUPPRESSED during iron deficiency — low iron → low hepcidin → more ferroportin → more absorption. A negative feedback loop matching absorption to need.
• Recycled iron from senescent RBC breakdown meets ~90% of daily needs; diet covers only the remainder.
• Vitamin C aids non-heme iron absorption by reducing Fe³⁺ to Fe²⁺.

Acts here

Where recycled iron comes from →Iron inserted into protoporphyrin IX →

FMK-09.2 slides 25–26

Two transporters, two diseases, opposite directions.

What it does

• MENKES — defective ATP7A impairs copper EFFLUX from enterocytes into portal blood. Copper is trapped in the gut lining and never reaches the body → systemic DEFICIENCY.
• WILSON — defective ATP7B impairs copper EFFLUX from the LIVER into bile. Copper accumulates in liver, then leaks into blood and deposits in brain, eyes, kidney and skin → OVERLOAD.

Deficiency — Menkes (deficiency) · Wilson (overload)

• MENKES: X-linked, presents in infancy. Progressive neurologic degeneration and connective tissue abnormalities — "kinky hair disease". Labs: LOW serum and urine copper, free and ceruloplasmin-bound.
• WILSON: autosomal recessive. Hepatic dysfunction, neuropsychiatric symptoms, KAYSER-FLEISCHER RINGS (corneal copper deposits). Labs: HIGH free copper in serum and urine.

MenkesA / WilsonB — ATP7A is Menkes, ATP7B is Wilson.

FMK-09.2 slide 27

One element, one gland, and a goiter at both ends of the axis.

What it does

• Required for synthesis of T3 (triiodothyronine) and T4 (thyroxine).
• THYROPEROXIDASE (TPO) does three sequential steps: oxidation of iodide, iodination of tyrosine residues on thyroglobulin, and coupling of iodinated tyrosines to form T3 or T4.
• ~90% of secreted hormone is T4; it is converted to the more active T3 in target tissues by SELENIUM-containing deiodinases.
• T3 binds a nuclear receptor, which binds the thyroid response element on DNA to regulate transcription.
• Axis: hypothalamic TRH → pituitary TSH → thyroid → T3/T4, with negative feedback on TRH and TSH.

Deficiency — Hypothyroidism / hyperthyroidism

• HYPOthyroidism — under-ingestion of iodine → compensatory TSH stimulation → GOITER. Fatigue, weight gain, decreased thermogenesis and metabolic rate. Congenital: irreversible intellectual disability and short stature if untreated. HASHIMOTO thyroiditis — autoimmune destruction of thyroid tissue/TPO — is the most common cause in iodine-sufficient regions.
• HYPERthyroidism — GRAVES disease, an autoantibody mimicking TSH, is the most common cause. Weight loss, heat intolerance, tachycardia, increased metabolic rate. EXOPHTHALMOS is distinctive to Graves specifically.

Pearls

• Goiter occurs in BOTH hypo- and hyperthyroidism — it is not a discriminator on its own.

FMK-09.2 slides 28–29