Vitamin A (retinol)
- Antioxidant- Constituent of visual pigments (combines with opsin to produce rhodopsin)- Essential for normal differentiation of epithelial cells into specialized tissue (pancreatic cells, mucus-secreting cells)- Prevents squamous metaplasia- Used to treat acne (oral isotretinoin), measles, and acute promyelocytic leukemia (APL) (all-trans retinoic acid) - Found in liver and leafy vegetables Deficiency:- Night blindness (nyctalopia)- Dry, scaly skin (xerosis cutis)- Corneal degeneration (keratomalacia)- Bitot spots (foamy appearance) on conjunctiva- Immunosuppression Excess:- Acute toxicity – nausea, vertigo, blurred vision- Chronic toxicity – alopecia, dry skin (eg, scaliness), hepatic toxicity and enlargement, arthralgias, and pseudotumor cerebri- Teratogenic (cleft plate, cardiac abnormalities)
Vitamin B1 (thiamine)
In thiamine pyrophosphate (TPP), a cofactor for several dehydrogenase enzyme reactions:- Pyruvate dehydrogenase (links glycolysis to TCA cycle)- α-ketoglutarate dehydrogenase (TCA cycle)- Transketolase (HMP shunt)- Branched-chain ketoacid dehydrogenase Deficiency- Impaired glucose breakdown → ATP depletion worsened by glucose infusion; highly aerobic tissues (eg, heart, brain) are affected first.- In alcoholic or malnourished patients, give thiamine before dextrose to ↓ risk of precipitating Wernicke encephalopathy.- Diagnosis made by ↑ in RBC transketolase activity following vitamin B1 administration. Wernicke-Korsakoff syndrome:- Triad: confusion + vision changes (ophthalmoplegia, nystagmus) + ataxia- Confabulation- Personality change- Memory loss (permanent)Damage to medial dorsal nucleus of the thalamus, mammillary bodies Wet beribery – high-output cardiac failure (dilated cardiomyopathy), edemaDry beriberi – polyneuropathy, symmetrical muscle wasting
Vitamin B2 (riboflavin)
Component of flavins FAD and FMN, used as cofactors in redox reactions eg, the succinate dehydrogenase reaction in the TCA cycle. Deficiency: - Individuals who do not consume dairy products (e.g., patients with lactose intolerance), and in individuals who do not eat meats or eggs. - Cheilosis (inflammation of the lips, scaling, fissures at the corners of the mouth)- Corneal vascularizationThe 2 Cs of B2- Glossitis- Stomatitis (hyperemic/edematous oropharyngeal mucous membranes, sore throat)- Normocytic-normochromic anemia- Seborrheic dermatitis Diagnosis: activity coefficient of erythrocyte glutathione reductase in the absence and presence of FAD
Vitamin B3 (niacin)
- Constituent of NAD+/NADP+ - Derived from tryptophan; synthesis requires vitamins B2 and B6- Used to treat dyslipidemia; lowers VLDL and raises HDL Deficiency:- Glossitis- Pellagra: diarrhea, dementia (also hallucinations), dermatitis ("broad collar" rash C3/C4 dermatome [Casal necklace], hyperpigmentation of sun-exposed limbs)- Can be caused by Hartnup disease (↓ tryptophan absorption), malignant carcinoid syndrome (↑ tryptophan metabolism), and isoniazid (↓ vitamin B6) Excess: Facial flushing (induced by prostaglandin, not histamine; can avoid by taking aspirin with niacin), hyperglycemia, hyperuricemia. (Deficiency → pellagra; excess → podagra). Hartnup disease – autosomal recessive deficiency of neutral amino acid (eg, tryptophan) transporters in proximal renal tubular cells and on enterocytes → neutral aminoaciduria and ↓ absorption from the gut → ↓ tryptophan for conversion to niacin → pellagra-like symptoms. Treat with high-protein diet and nicotinic acid.
Vitamin B6 (pyridoxine)
- Converted to pyridoxal phosphate (PLP), a cofactor used in transamination (eg, ALT and AST), decarboxylation reactions, glycogen phosphorylase.- Synthesis of cystathionine, heme, niacin, histamine, and neurotransmitters including serotonin, epinephrine, norepinephrine, dopamine, and GABA. Deficiency:- Convulsions, hyperirritability, peripheral neuropathy (deficieny inducible by isoniazid and oral contraceptives)- Sideroblastic anemias (due to impaired hemoglobin synthesis and iron excess).
Vitamin B7 (biotin)
Cofactor for carboxylation enzymes (which add a 1-carbon group):- Pyruvate carboxylase: pyruvate (3C) → oxaloacetate (4C)- Acetyl-CoA carboxylase: acetyl CoA (2C) → malonyl-CoA (3C)- Propionyl-CoA carboxylase: proprionyl-CoA (3C) → methylmalonyl-CoA (4C) Deficiency:- Relatively rare - Dermatitis, alopecia, enteritis- Caused by antibiotic use or excessive consumption of raw egg whites [contains avidin])
Vitamin B9 (folate)
Converted to tetrahydrofolic acid (THF), a coenzyme for 1-carbon transfer/methylation reactions.- Important for the synthesis of nitrogenous bases in DNA and RNA. - Found in leafy green vegetables. - Absorbed in jejunum. Small reserve pool stored primarily in the liver. Deficiency:- Macrocytic, megaloblastic anemia; hypersegmented polymorphonuclear cells (PMNs)- Glossitis- No neurologic symptoms (as opposed to vitamin B12 deficiency)- Labs: ↑ homocysteine, normal methylmalonic acid levels- Seen in alcoholism and pregnancy - Deficiency can be caused by drugs (eg, phenytoin, sulfonamides, methotrexate). - Supplemental maternal folic acid at least 1 month prior to conception and during early pregnancy ↓ risk of neural tube defects.
Vitamin B12 (cobalamin)
Cofactor for methionine synthase (transfers CH3 groups as methylcobalamine) and methylmalonyl-CoA mutase. Important for DNA synthesis. - Found in animal products. Synthesized only by microorganisms. - Very large reserve pool (several years) stored primarily in the liver. Deficiency:- Macrocytic, megaloblastic anemia; hypersegmented PMNs- Paresthesias and subacute combined degeneration (degeneration of dorsal columns, lateral corticospinal tracts, and spinocerebellar tracts) due to abnormal myelin.- ↑ serum homocysteine and methylmalonic acid levels, along with 2˚ folate deficiency.- Prolonged deficiency → irreversible nerve damage. - Deficiency caused by malabsorption (eg, sprue, enteritis, Diphyllobothrium latum, achlorhydria, bacterial overgrowth, alcohol excess), lack of intrinsic factor (eg, pernicious anemia, gastric bypass surgery), absence of terminal ileum (surgical resection, eg, for Crohn disease), or insufficient intake (eg, veganism).- Anti-intrinsic factor antibodies diagnostic for pernicious anemia.- Folate supplementation can mask the hematologic symptoms of B12 deficiecny, but not the neruologic symptoms.
Vitamin C (ascorbic acid)
- Antioxidant- Facilitates iron absorption by reducing it to Fe2+ state- Necessary for hydroxylation of proline and lysine in collagen synthesis- Necessary for dopamine β-hydroxylase (converts dopamine to NE)- Ancillary treatment for methemoglobinemia by reducing Fe3+ to Fe2+ - Found in fruits and vegetables Deficiency: Scurvy- Swollen gums- Bruising, petechia, hemarthrosis- Anemia- Poor wound healing- Perifollicular and subperiosteal hemorrhages- "Corkscrew" hair- Weakened immune response Excess: Nausea, vomiting, diarrhea, calcium oxalate nephrolithiasis- Can ↑ risk of iron toxicity in predisposed individuals by increasing dietary iron absorption (ie, can worsen hereditary hemochromatosis or transfusion-related iron overload).
Vitamin D
D3 (cholecalciferol) from exposure of skin (stratum basale) to sun, ingestion of fish, milk, plants.D2 (ergocalciferol) from ingestion of plants, fungi, yeasts.Both converted to 25-OH D3 (storage form) in liver and to the active form 1,25-(OH)2 D3 (calcitriol) in kidney. - ↑ intestinal absorption of Ca2+ and PO43-- ↑ bone mineralization- ↑ bone resorption at higher levels- ↑ PTH → ↑ Ca2+ reabsorption and ↓ PO43- reabsorption in the kidney. Deficiency:- Rickets in children (bone deformity, such as genu varum "bow legs")- Osteomalacia in adults (bone pain and muscle weakness)- Hypocalcemic tetany- Caused by malabsorption, ↓ sun exposure, poor diet, chronic kidney disease - Deficiency is exacerbated by pigmented skin, premature birth.- Give oral vitamin D to breastfed infants. Excess: Hypercalcemia, hypercalciuria, loss of appetite, stupor. Seen in granulomatous disease (↑ activation of vitamin D by epithelioid macrophages).
Vitamin E (tocopherol)
Antioxidant (protects RBCs and membranes from free radical damage). Deficiency:- Hemolytic anaemia- Acanthocytosis- Muscle weakness- Posterior column and spinocerebellar tract demyelination→ Neurologic presentation may appear similar to vitamin B12 deficiency, but without megloblastic anemia, hypersegmented neutrophils, or ↑ serum methylmalonic levels. Excess: - Risk of enterocolitis in infants- High-dose supplementation may alter metabolism of vitamin K → enhanced anticoagulant effects of warfarin.
Vitamin K (phytomenadione)
Includes phytomenadione, phylloquinone, phytonadione, menaquinone.Activated by epoxide reductase to the reduced form, which is a cofactor for the γ-carboxylation of glutamic acid residues on proteins required for blood clotting (II, VII, IX, X, proteins C and S).- Synthesized by intestinal flora. Deficiency:- Neonatal hemorrhage with ↑ PT and ↑ aPTT but normal bleeding time (neonates have sterile intestines and are unable to synthesize vitamin K).- Can also occur after prolonged use of broad-spectrum antibiotics. - Not in breast milk; neonates are given vitamin K injection at birth to prevent hemorrhagic disease of the newborn.
Vitamin B5 (pantothenic acid)
Essential component of coenzyme A (CoA, a cofactor for acyl transfers) and fatty acid synthase. Deficiency:- Dermatitis- Enteritis- Alopecia- Adrenal insufficiency
Ethanol metabolism
Ethanol → Acetaldehyd occurs in cytosol, microsomes (via CYP2E1 and NADPH), peroxisomes (via catalase and H2O2).Acetaldehyde → Acetate occurs in mitochondria. Fomepizole – inhibits alcohol dehydrogenase and is an antidote for methanol or ethylene glycol poisoning.Disulfiram – inhibits acetaldehyd dehydrogenase (acetaldehyde accumulates, contributing to hangover symptoms), discourages drinking. - NAD+ is the limiting reagent.- Alcohol dehydrogenase operates via zero-order kinetics. Ethanol metabolism ↑ NADH/NAD+ ratio in liver, causing:- Pyruvate → lactate (lactate acidosis)- Oxaloacetate → malate (prevents gluconeogenesis → fasting hypoglycemia)- Dihydroxyacetone phosphate → glycerol-3-phosphate (combines with fatty acids to make triglycerides → hepatosteatosis)- Disfavors TCA production of NADH → ↑ utilization of acetyl-CoA for ketogenesis (→ ketoacidosis) and lipogenesis (→ hepatosteatosis)
Zinc
Mineral essential for the activity of 100+ enzymes. Important in the formation of zinc fingers (transcription factor motif). Cause: Long-term total parenteral nutrition, malabsorptive pathology Deficiency: - Triad: Dermatitis, diarrhea, alopezia- Delayed wound healing- Suppressed immunity- Hypogonadism- ↓ adult hair (axillary, facial, pubic)- Dysgeusia- Anosmia- Acrodermatitis enteropathica- May predispose to alcoholic cirrhosis
Protein-energy malnutrition
Kwashiorkor:- Protein malnutrition resulting in skin lesions, edema due to ↓ plasma oncotic pressure, liver malfunction (fatty change due to ↓ apolipoprotein synthesis).- Clinical picture is small child with swollen abdomen. Marasmus:- Malnutrition not causing edema.- Diet is deficient in calories but no nutrients are entirely absent.- Muscle wasting
Vitamins: water soluble
B1 (thiamine: TPP)B2 (riboflavin: FAD, FMN)B3 (niacin: NAD+)B5 (pantothenic acid: CoA)B6 (pyridoxine: PLP)B7 (biotin)B9 (folate)B12 (cobalamin)C (ascorbic acid) - All wash out easily from body except B12 (stored in liver for ~3-4 years) and B9 (stored in liver for ~3-4 months).- B-complex deficiencies often result in dermatitis, glossitis, and diarrhea.- Can be coenzymes (eg, ascorbic acid) or precursors to organic cofactors (eg, FAD, NAD+).
Vitamins: fat soluble
A, D, E, K. Absorption dependent on gut and pancreas. Toxicity more common than for water-soluble vitamins because fat-soluble vitamins accumulate in fat. Malabsorption syndromes with steatorrhea (eg, cystic fibrosis and celiac disease) or mineral oil intake can cause fat-soluble vitamin deficiencies.
