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Uracil Metabolism—UMP Synthesis from Orotic Acid or Uridine and Conversion of Uracil to β-Alanine: Enzymes and cDNAs

1996; Academic Press; Linguagem: Inglês

10.1016/s0079-6603(08)60142-7

2211-9108

Thomas W. Traut, Mary Ellen Jones,

Enzyme Structure and Function

The importance of maintaining balanced pyrimidine nucleotide metabolism is evident because it has been shown that many biosynthetic pathways are dependent on pyrimidines. Pyrimidine nucleotides are also important for the continued biosynthesis of various macromolecules, such as phospholipids and polysaccharides, for which specific nucleotides are required as cofactors in activating appropriate precursors, as exemplified by CMP-choline and UDP-glucose. Even the conversion of uracil to β-alanine is a biosynthetic pathway, although historically this has been referred to as catabolism. A biosynthetic designation for this pathway comes from the importance of β-alanine, which functions as a neurotransmitter, as well as a building block for various dipeptides. These peptides include the ubiquitous pantothenate, the precursor for the acyl-carrier protein in fatty acid synthase and for coenzyme A. The inability of humans to synthesize pantothenate makes it a vitamin. The biochemical roles of carnosine and other dipeptides containing β-alanine are discussed in the chapter. Nucleotides presumably exist at very low concentrations in the extracellular environment, though no values have been published for their concentration in blood. DNA sequencing suggests that many mammalian or human proteins may be coded by two or more genes, and that such gene duplication may provide a simple safety factor in the event of a mutation in one gene, or provide a more sophisticated regulatory strategy if the genes lead to slightly altered isozymes to be expressed in unique tissues.