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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Abstract of Dissertation Presented to the Graduate School<br />
of the University of Florida in Partial Fulfillment of the<br />
Requirements for the Degree of Doctor of Philosophy<br />
<strong>B12</strong> <strong>METABOLISM</strong> <strong>IN</strong> <strong>HUMANS</strong><br />
<strong>By</strong><br />
Nicole Aurora Leal<br />
August 2004<br />
Chair: Thomas A. Bobik<br />
Major Department: Microbiology and Cell Science<br />
In humans, the <strong>B12</strong> coenzymes, adenosylcobalamin and methylcobalamin, are<br />
required cofactors for propionate metabolism and methionine biosynthesis, respectively.<br />
Humans are incapable of de novo synthesis of the <strong>B12</strong> coenzymes and require complex<br />
precursors such as vitamin <strong>B12</strong> in their diet. The metabolism of vitamin <strong>B12</strong> to<br />
adenosylcobalamin requires two successive reductions and an adenosylation reaction;<br />
however, many aspects of the genetics and biochemistry of this process have not been<br />
elucidated. This dissertation focuses on the isolation and characterization of the human<br />
genes and enzymes involved in the formation of adenosylcobalamin from vitamin <strong>B12</strong>.<br />
Deficiencies in this process result in methylmalonic aciduria, a rare disorder that is often<br />
fatal in newborns.<br />
Because of the sophisticated genetic methods that are available, Salmonella<br />
enterica was used as a model system. <strong>By</strong> complementation of an S. enterica mutant, a<br />
bovine adenosyltransferase cDNAs was isolated and subsequent sequence similarity<br />
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