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Digestion/Absorption: Vitamins (water-soluble (abs. in SI via, specific…
Digestion/Absorption: Vitamins
water-soluble
abs. in SI via
specific carriers and/or
brush border & luminal enzymes >> deconjugation or phosphorylation
many Na-dependent
many utilize GPCR & cAMP
fat-soluble
rely on lipid abs. process d/t chem. structure
protein haptens >> proteolysis by gastric juices >> taken into emulsion droplets in SI >> simple diffusion into enterocytes or via transporters
once in enterocyte >> diffuse to SER (via specific carrier proteins; i.e. retinol-binding protein) >> + lipid droplets >> chylomicrons or VLDLs >> to Golgi >> to lymph
once in lymph >> systemic blood >> liver thru receptor mediated endocytosis of chylomicrons
rates vary; modulated by other vitamins & drugs
deficiencies d/t malabsorption
bariatric surgery
drugs that impair hydrolysis or bile acids
impaired hepatobiliary fxn
unabsorbable fat substrates
Tx: water-miscible emulsions of the vitamin(s) >> adds more polar group
Folate
deficiency >> neural tube defects in developing fetus (spina bifida & anencephaly)
Tetrahydrafolate (THF)
reduced, biochemically active form
cofactor
synthesis of thymine & purines
deficiency >> inhibited DNA synthesis;
megaloblastic anemia
(large RBCs & WBCs in blood & BM d/t uninhibited protein & RNA synthesis)
Tx: pteroylmonoglutamate (PteGlu1)
digestion:
dietary as folate polyglutamate (PteGlu7)
folate conjugase
>> removes glutamate residues one by one >> PteGlu1
absorption:
unknown mechanism for basolateral transport
in liver, enzymatically changed to THF
PteGlu1 carrier >> into enterocytes in SI
Vit. B12 (Cobalamin)
only synthesized by microbes
found in animal products
coenzyme: transfers methyl group to homocysteine >> methionine
methionine
essential a.a.
deficiency >> body usues intracellular folate stores
deficiency due to:
megaloblastic anemia
vegetarian diet
pernicious anemia
d/t lack of parietal cells in elderly
d/t atrophy or
Ab-mediated immune response against parietal cells or IF
results: no IF secretion >> no B12 absorption
molecular mimicry from H. pylori infection
: Ab against H.pylori attack parietal cells
Tx: hydroxycobalamin IM injections
Dx:
Schilling Test for IF deficiency
bacteria in SI (bind & metabolize)
Crohn disease
Ileal resection
absorption:
B12:protein haptens >> pepsin & low pH in stomach >> releases B12
HCO3 & proteases from pancreas >> releases B12
B12:IF (secreted in stomach; inactive until SI) >> binds IF receptors in ileum >> endocytosis
once in enterocyte >> B12:IF dissociate >> B12:transcobalamin II >> basolateral exit
to liver via hepatic circulation >> XS cobalamin secreted into bile; bile & diet cobalamin in SI equal d/t low dietary intake
gastric glands secrete haptocorrin & parietal cells secrete I.F. >> haptocorrin:B12