Overview vitamin algorithm Examples A D E K Characteristics precursors for coenzymes pancreatic enzymes required for absorption in the ileum malabsorption syndromes can cause fat-soluble vitamin deficiencies e.g. steatorrhea, cystic fibrosis, and sprue stored in fat making toxicity possible (unlike water soluble vitamins) Vitamin A (Retinol) Function antioxidant neutralize free radicals constituent of visual pigments (retinal) β-carotene from diet enzymatically converted to cis-retinal, which undergoes photoisomerization to trans-retinal when light is absorbed co-factor for protein rhodopsin essential for normal differentiation of epithelial cells into specialized tissue pancreatic and mucus-secreting cells binds intracellular receptors that regulate transcription at the retinoic acid response elements immune system stimulation stimulates T-cell differentiation and proliferation vitamin A supplementation recommended for measles treatment retinitis pigmentosa vitamin A supplementation used as a treatment in retinitis pigmentosa (usually autosomal dominant) Source found in liver and green/yellow vegetables β-carotene also a source dimer of retinal that must be cleaved and converted to trans-retinol for intestinal absorption isotretinoin form of retinoic acid used in treatment of acne Deficiency causes deficiency in dietary intake due to storage in fat must occur over several months malabsorption fat-free diets night blindness xerophthalmia squamous metaplasia of corneal epithelium spots are known as Bitot spots follicular hyperkeratosis dry skin due to loss of sebaceous gland function frequent infections Excess causes over supplementation regular intake > 15 x RDA consumption of wild game liver isotretinoin treatment symptoms arthralgias periosteal proliferation alopecia papilledema and seizures result of intracranial swelling skin changes yellow pigment with excess β-carotene but sclera remain white contrasted with jaundice which sclera and skin turn yellow teratogenic cleft palate and cardiac abnormalities a pregnancy test must be done before isotretinoin is prescribed for severe acne Vitamin D Function raise low blood calcium concentrations ↑ duodenal absorption of calcium and phosphate ↑ reabsorption of calcium from distal renal tubules ↑ bone resorption via activation of osteoclasts bisphosphonates inhibit activation of osteoclasts and ↓ bone resorption e.g., ibandronate, risedronate, and alendronate remodeling of bone osteoblasts have receptors for vitamin D binding stimulates release of alkaline phosphatase (alk-phos) alk-phos dephosphorylates pyrophosphate pyrophosphate normally inhibits bone mineralization matures macrophage stem cells into osteoclasts Source pre-formed ingestion in diet D2 = ergocalciferol ingested from plants used as pharmacologic agent D3 = cholecalciferol consumed in milk and fish formed in sun-exposed skin 7-dehydrocholesterol → cholecalciferol (D3) in skin catalyzed by UV light step insufficient in climates where low temperatures do not allow for sun exposure cholecalciferol (D3) → 25-hydroxycholecalciferol (25-OH D3) in liver catalyzed by 25-hydroxylase decrease in hepatic function may result in vitamin D deficiency must supplement with 25-OH D3 occurs in the P450 system 25-OH D3→ 1,25-dihydroxycholecalciferol (1,25-(OH)2 D3) in kidney catalyzed by 1α-hydroxylase 1α-hydroxylase upregulated by PTH in response to hypocalcemia decrease in renal function may result in vitamin D deficiency pseudo-vitamin D deficiency rickets hereditary deficiency in 1α-hydroxylase must supplement with 1,25-(OH)2 D3 equivalent 25-OH D3 = storage form 1,25-(OH)2 D3 (calcitriol) = active form Deficiency causes low sunlight exposures hepatic or renal function decrease fat malabsorption induction of P450 which degrades active vitamin D precursors exclusive breastfeeding symptoms rickets in children (bending bones) osteomalacia in adults (soft bones) hypocalcemic tetany Excess causes supplementation > 10x RDA seen in sarcoidosis ↑ activation of vitamin D by epithelioid macrophages symptoms polyuria, polydipsia, and nocturia hypercalcemia and hypercalciuria high blood calcium concentration promotes metastatic calcification loss of appetite and stupor high levels of vitamin D promote bone resorption Vitamin E (α-tocopherol) Function antioxidant prevents peroxidation of fatty acids allowing membranes to maintain normal fluidity prevents oxidation of LDL protects against arteriosclerosis Deficiency rare causes fat malabsorption abetaliproteinemia symptoms ↑ fragility of erythrocytes (hemolytic anemia) muscle weakness neurodysfunction poor joint sensation and ataxia Excess synergistic ↓ in vitamin K dependent clotting factors with warfarin potential hemorrhage in warfarin patients Vitamin K Function catalyzes γ-carboxylation of glutamic acid residues on blood clotting proteins cofactor for γ-glutamyl carboxylase allows Ca2+ binding site co-translational modification in RER necessary for the synthesis of clotting factors II (prothrombin), VII, IX, X, and protein C and S must be activated by epoxide reductase enzymes inhibited by warfarin, which is a vitamin K antagonist an anticoagulant in vivo (not in vitro) 2-3 days required to achieve anticoagulation heparin given for immediate results Source normal gut bacterial flora green vegetables breast milk does NOT contain vitamin K Deficiency causes fat malabsorption neonates have sterile intestines and are unable to synthesize vitamin K aggravated by mothers who took anticonvulsants during pregnancy neonates are given vitamin K injection at birth to prevent hemorrhage can also occur after prolonged use of broad-spectrum antibiotics destruction of normal gut flora ↓ in hepatic function can ↓ vitamin K activation symptoms ↑ PT and normal aPTT, but normal bleeding time (can also see increased aPTT, but as factor VII has the shortest half-life, PT increases before aPTT) easy bruising and bleeding hemorrhagic disease of the newborn Excess rare symptoms hemolytic anemia and liver damage