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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Studies also indicated that humans have redundant systems for mitochondrial<br />
cob(II)alamin reduction. Prior complementation analysis demonstrated that cblE (MSR)<br />
disorders usually result in homocystinuria without methylmalonic aciduria with only one<br />
reported case having both homocystinuria and mild methylmalonic aciduria (Wilson et al.<br />
1999). The fact that most cblE patients lack methylmalonic aciduria suggests that there<br />
are redundant mitochondrial cob(II)alamin reductase(s) involved in AdoCbl synthesis.<br />
There is precedence for redundant cobalamin reductases in bacteria. The role of MSR<br />
could be to provide extra capacity under certain conditions, such as a high protein diet,<br />
rich in amino acids that are metabolized via the propionyl-CoA pathway.<br />
Future Experimentation<br />
The development of the screening method employed in this study can be used in<br />
the future as a general technique for the isolation of other cDNAs involved in cobalamin<br />
metabolism. Salmonella is an excellent model system for these studies since<br />
AdoCbl-dependent diol dehydratase for 1,2-propanediol degradation has been well<br />
studied. Once other enzymes involved in cobalamin metabolism are identified in<br />
S. enterica, strains deficient in these activities can be used to screen mammalian<br />
expression libraries by complementation. Hence, this technique may allow for the<br />
identification of other genes crucial for cobalamin metabolism in eukaryotic systems.<br />
Now that a purification method has been developed for the ATR, efforts can be<br />
focused on crystallizing this protein. Determining the three dimensional structure of the<br />
ATR will allow us to understand how mutations in this enzyme lead to dysfunction by<br />
comparing amino acid residues in normal and mutant ATRs and mapping the altered<br />
amino acid residues onto the structure. Potentially, this process would help lend insight<br />
in identifying the residues of the ATR that are crucial for enzymatic activity.