Four vitamins are fat-soluble: A, D, E, K. They are stored in body fat and the liver. Because they are not excreted readily, excess intake can be toxic (unlike water-soluble vitamins, where excess is urinated out). Absorption requires bile acids, so fat malabsorption (e.g., from pancreatic or biliary disease) can lead to deficiency.
Vitamin A (Retinol)
Role: vision (retinal is the chromophore in rhodopsin), growth, immune function, epithelial maintenance.
Deficiency: night blindness (the first sign), xerophthalmia (dry, damaged cornea), impaired immunity.
Sources: liver, eggs, dairy, carotenoids from orange/green vegetables (beta-carotene is cleaved into retinol).
Vitamin D (Cholecalciferol)
Role: calcium and phosphate homeostasis, bone mineralization. Technically a steroid hormone.
Deficiency: rickets in children (bowing of growing bones), osteomalacia in adults.
Sources: sunlight converts 7-dehydrocholesterol to cholecalciferol in skin; also in fatty fish, egg yolks, fortified milk.
Biochemically, vitamin D is activated by two hydroxylations: first in the liver (25-hydroxylation) and then in the kidney (1-alpha-hydroxylation) to produce the active 1,25-dihydroxyvitamin D. This active form binds nuclear receptors and upregulates genes for calcium absorption in the gut.
Vitamin E (Tocopherol)
Role: membrane antioxidant. Quenches lipid peroxyl radicals in membranes, protecting unsaturated fatty acids from oxidative damage.
Deficiency: hemolytic anemia (red cell membranes oxidize and lyse), neuromuscular symptoms (rare in developed countries).
Sources: vegetable oils, nuts, seeds.
Vitamin K (Phylloquinone)
Role: cofactor for gamma-carboxylation of clotting factors II, VII, IX, X, and proteins C and S. Without vitamin K, these factors cannot bind calcium and clot formation fails.
Deficiency: bleeding, bruising. Newborns are routinely given vitamin K at birth because they have limited stores and no gut bacteria yet.
Sources: leafy green vegetables, made by gut flora.
Warfarin, an anticoagulant, blocks vitamin K recycling (vitamin K epoxide reductase), leading to non-functional clotting factors and reduced coagulation.
Which four vitamins are fat-soluble, and why is it important that they are?
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Vitamins A, D, E, and K. Because they are fat-soluble, they require bile acids for intestinal absorption and can be stored in body fat and the liver. Excess can be toxic (unlike water-soluble vitamins, which are excreted in urine). Fat malabsorption (from pancreatic disease, biliary obstruction, etc.) causes deficiency of all four as a group.
What is the biochemical role of vitamin K, and how does warfarin interfere with it?
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Vitamin K is a cofactor for gamma-carboxylation of glutamate residues in clotting factors II, VII, IX, X (and proteins C and S). The gamma-carboxylation is required for the factors to bind calcium and participate in clotting. Warfarin blocks the recycling of vitamin K (inhibits vitamin K epoxide reductase), depleting the active form and producing non-functional clotting factors - the basis for warfarin's anticoagulant effect.
A patient with long-standing cystic fibrosis develops night blindness, bowing of the legs, and easy bruising. What is the unifying cause?
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Fat-soluble vitamin deficiency due to fat malabsorption. CF causes pancreatic insufficiency - not enough lipase and other digestive enzymes reach the gut. Dietary fat cannot be absorbed, so the fat-soluble vitamins go with it. Night blindness (vitamin A), bowing legs/osteomalacia (vitamin D), and easy bruising (vitamin K) are all classic. Vitamin E deficiency may also contribute.
