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 login to view 1 more bullet 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 login to view 1 more bullet malabsorption fat-free diets night blindness xerophthalmia squamous metaplasia of corneal epithelium login to view 1 more bullet follicular hyperkeratosis login to view 1 more bullet frequent infections Excess causes over supplementation login to view 1 more bullet consumption of wild game liver isotretinoin treatment symptoms arthralgias login to view 1 more bullet alopecia papilledema and seizures login to view 1 more bullet skin changes login to view 2 more bullets 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 login to view 2 more bullets remodeling of bone osteoblasts have receptors for vitamin D binding stimulates release of alkaline phosphatase (alk-phos) alk-phos dephosphorylates pyrophosphate login to view 1 more bullet matures macrophage stem cells into osteoclasts Source pre-formed ingestion in diet D2 = ergocalciferol login to view 2 more bullets D3 = cholecalciferol login to view 1 more bullet formed in sun-exposed skin 7-dehydrocholesterol → cholecalciferol (D3) in skin catalyzed by UV light login to view 1 more bullet cholecalciferol (D3) → 25-hydroxycholecalciferol (25-OH D3) in liver catalyzed by 25-hydroxylase login to view 3 more bullets 25-OH D3→ 1,25-dihydroxycholecalciferol (1,25-(OH)2 D3) in kidney catalyzed by 1α-hydroxylase login to view 5 more bullets 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 login to view 1 more bullet symptoms polyuria, polydipsia, and nocturia hypercalcemia and hypercalciuria login to view 1 more bullet 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 login to view 1 more bullet symptoms ↑ fragility of erythrocytes (hemolytic anemia) muscle weakness neurodysfunction login to view 1 more bullet 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 login to view 1 more bullet 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 login to view 2 more bullets can also occur after prolonged use of broad-spectrum antibiotics login to view 1 more bullet ↓ 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) login to view 2 more bullets Excess rare symptoms hemolytic anemia and liver damage