Vitamin Lysosomes

The most clearly documented role lor selenium is as a necessary component of glutathione peroxidase. Selenium is also involved in the functions of additional enzymes, e.g.. type I iodoihvronine deiodinase. leukocyte acid phosphatase, and glucuronidases. A role for selenium in electron transfer has been suggested as has involvement in nonheme iron proteins. Selenium and vitamin b appear to be necessary lor proper functioning of lysosomal membranes. A role for selenium in metabolism of thyroid hormone has been continued. 

The TCII-vitamin B12 complex is recognized by specific high-affinity plasma membrane receptors present on the cells that utilize vitamin B12. After internalization, the complex is transferred to lysosomes, where TCII is rapidly degraded, and the hydroxycobalamin is released into the cytosol and methylated. The hydroxycobalamin that enters the mitochondria... 

Within the ileal mucosal cell, the vitamin is released by lysosomal proteolysis of intrinsic factor, and is bound to transcobalamin II, a vitamin B12 binding protein synthesized in the enterocytes. Transcobalamin II is in vesicles destined for export from the enterocytes, and it is assumed that vitamin B12 binds to the apoprotein in these vesicles rather than in the lysosomes, because otherwise newly synthesized transcobalamin would be hydrolyzed by lysosomal proteases (Seetharam, 1999). 

Dietary biotin bound to avidin (Section 11.6) is unavailable, but intravenously administered avidin-biotin is biologically active. Cells in culture are not inhibited by the addibon of avidin to the culmre medium, and can take up the avidin-biotin complex by pinocytosis followed by lysosomal hydrolysis, releasing free biotin. Unlike other B vitamins, for which concentrative uptake into tissues is achieved by facilitated diffusion, followed by metabolic trapping, the incorporation of biotin into enzymes is slow and cannot be considered part of the uptake process. 

The place and importance of these enzymes in the process of normal keratinization and in psoriasis is still obscure however, the fact that vitamin A-acid has been used to treat psoriasis successfully and is a lysosomal labilizer (F21) may indicate that they are of great importance. 

Vitamin A is a surfactant, and its toxicity may be due to labilization and disruption of biological membranes. Excessive amounts of retinol also increase synthesis and release of lysosomal hydrolases. In in vitro systems, retinol bound to RBP is not toxic, and RBP alone protects against... 

TCII plays a major role in transport of cobalamins to tissues. A receptor for the TCII-B12 complex has been tentatively identified in vitro on HeLa cells,Ehrlich ascites cells,and human fibroblasts. The bound complex is transferred into the cell, where the cobalamin is released and the TCII is degraded in lysosomes (Figure 38-18). An inborn error of vitamin Bj2 metabolism has been attributed to a defect in vitamin B12 release from lysosomes. A congenital... 

Plausible as the above mechanism may seem, it may, however, not be the whole truth. An alternative mechanism is vesicular transport. In chicken intestine it has been shown that the only epithelial organelles that increased in Ca content as a result of calcitriol treatment were the lysosomes." The result lends support to a transport mechanism involving Ca + uptake across the brush-border membrane by endocytic vesicles, fusion of these vesicles with lysosomes, and possibly also delivery of Ca to the basal lateral membrane of the epithelial cell by exocytosis. This process would also explain the vitamin-D-induced alterations in brush-border-membrane lipid compositions as a consequences of preferential incorporation of certain types of lipids into the vesicles. Interestingly, the lysosomes in the chicken studies also contained high levels of calbin-... 

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