B12 METABOLISM IN HUMANS By NICOLE AURORA LEAL A ...
B12 METABOLISM IN HUMANS By NICOLE AURORA LEAL A ...
B12 METABOLISM IN HUMANS By NICOLE AURORA LEAL A ...
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folate-dependent reactions including purine and pyrimidine biosynthesis (Wilson et al.<br />
1999).<br />
Cobalamin Absorption and Transport<br />
11<br />
As mentioned above, humans are incapable of de novo cobalamin synthesis, and<br />
require complex precursors in their diet. Suitable precursors (such as HOCbl or CNCbl)<br />
can be obtained by the consumption of beef, liver, poultry, fish, eggs, dairy products, and<br />
vitamin supplements (Stabler 1999). The cobalt of these cobalamin molecules is in the<br />
+3 oxidation state (cob(III)alamin), the form that is recognized for cobalamin absorption<br />
and transport. Once ingested, cobalamin molecules that are bound to food proteins are<br />
released by the combined action of proteases and acid in the stomach (Del Corral and<br />
Carmel 1990). Haptocorrin (a cobalamin carrier protein) binds released cobalamin and<br />
transports it from the stomach to the small intestines. Haptocorrin has a high specificity<br />
for cobalamin and when bound to cobalamin, protects it from damage by acids in the<br />
stomach, until it reaches the small intestines where cobalamin is liberated from<br />
haptocorrin via digestion by pancreatic enzymes. After being released from haptocorrin,<br />
cobalamin is bound by intrinsic factor (IF), a glycoprotein produced by the parietal cells<br />
(gastric glands lining the stomach). The IF-cobalamin complex is resistant to further<br />
digestion in the small intestines because of the carbohydrates on the IF. The<br />
IF-cobalamin complex recognizes the IF-cobalamin receptor (IFCR) on the epithelial<br />
cells of the distal third small intestines (ileum), and is transported into these cells via<br />
receptor-mediated endocytosis. In the epithelial cell, IF is degraded by the acidic<br />
environment of the lysosome, and cobalamin is released. Transcobalamin II (TCII), a<br />
serum-transport protein in the epithelial cells, binds released cobalamin, and transports it<br />
out of the cell and into the bloodstream until it is taken up by other cells. The