A "neural" enzyme in nonbilaterian animals and algae: preneural origins for peptidylglycine alpha-amidating monooxygenase.
(17/31)
Secreted peptides, produced by enzymatic processing of larger precursor molecules, are found throughout the animal kingdom and play important regulatory roles as neurotransmitters and hormones. Many require a carboxy-terminal modification, involving the conversion of a glycine residue into an alpha-amide, for their biological activity. Two sequential enzymatic activities catalyze this conversion: a monooxygenase (peptidylglycine alpha-hydroxylating monooxygenase or PHM) and an amidating lyase (peptidyl-alpha-hydroxyglycine alpha-amidating lyase or PAL). In vertebrates, these activities reside in a single polypeptide known as peptidylglycine alpha-amidating monooxygenase (PAM), which has been extensively studied in the context of neuropeptide modification. Bifunctional PAMs have been reported from some invertebrates, but the phylogenetic distribution of PAMs and their evolutionary relationship to PALs and PHMs is unclear. Here, we report sequence and expression data for two PAMs from the coral Acropora millepora (Anthozoa, Cnidaria), as well as providing a comprehensive survey of the available sequence data from other organisms. These analyses indicate that bifunctional PAMs predate the origins of the nervous and endocrine systems, consistent with the idea that within the Metazoa their ancestral function may have been to amidate epitheliopeptides. More surprisingly, the phylogenomic survey also revealed the presence of PAMs in green algae (but not in higher plants or fungi), implying that the bifunctional enzyme either predates the plant/animal divergence and has subsequently been lost in a number of lineages or perhaps that convergent evolution or lateral gene transfer has occurred. This finding is consistent with recent discoveries that other molecules once thought of as "neural" predate nervous systems. (+info)
Exome array analysis identifies new loci and low-frequency variants influencing insulin processing and secretion.
(18/31)
Peroxisomal localization and activation by bivalent metal ions of ureidoglycolate lyase, the enzyme involved in urate degradation in Candida tropicalis.
(21/31)
Ureiodoglycolate lyase (EC 4.3.2.3) was found only in the peroxisomes in urate-induced Candida tropicalis. The enzyme was markedly activated by the bivalent metal ions Mn2+, Fe2+, and Ni2+. The activation by Mn2+ was suggested to be the result of its binding to the apoenzyme. (+info)
Ureidoglycollate lyase, a new metalloenzyme of peroxisomal urate degradation in marine fish liver.
(22/31)
Ureidoglycollate lyase (UGL, EC 4.3.2.3), which catalyses the degradation of S(-)-ureidoglycollate to urea and glyoxylate, was found in the peroxisomes of marine fish (sardine and mackerel) liver. The enzyme highly purified from sardine liver had an Mr of about 121,000, with two identical subunits. When UGL was purified in the presence of 1 mM-EDTA, a much less active form was obtained. It was markedly activated by bivalent metal ions, particularly by Mn2+. The Mn2+-activated enzyme remained active when free Mn2+ was removed by gel filtration on Sephadex G-50, suggesting that UGL may be a metalloenzyme and the activation resulted from the binding of Mn2+ to the apoenzyme. UGL was found to be essential in peroxisomal urate degradation, since allantoate, the intermediate of urate catabolism, was found to be degraded to urea and glyoxylate in a two-step reaction catalysed by allantoicase (EC 3.5.1.5) and UGL via S(-)-ureidoglycollate as an intermediate in fish liver peroxisomes, but not in a one-step reaction as previously believed. (+info)
Identification of the ureidoglycolate hydrolase gene in the DAL gene cluster of Saccharomyces cerevisiae.
(23/31)
This report describes the isolation of the genes encoding allantoicase (DAL2) and ureidoglycolate hydrolase (DAL3), which are components of the large DAL gene cluster on the right arm of chromosome IX of Saccharomyces cerevisiae. During this work a new gene (DAL7) was identified and found to be regulated in the manner expected for an allantoin pathway gene. Its expression was (i) induced by allophanate, (ii) sensitive to nitrogen catabolite repression, and (iii) responsive to mutation of the DAL80 and DAL81 loci, which have previously been shown to regulate the allantoin degradation system. Hybridization probes generated from these cloned genes were used to analyze expression of the allantoin pathway genes in wild-type and mutant cells grown under a variety of physiological conditions. When comparison was possible, the patterns of mRNA and enzyme levels observed in various strains and physiological conditions were very similar, suggesting that the system is predominantly regulated at the level of gene expression. Although all of the genes seem to be controlled by a common mechanism, their detailed patterns of expression were, at the same time, highly individual and diverse. (+info)
The all2 gene is required for the induction of the purine deamination pathway in Schizosaccharomyces pombe.
(24/31)
Five mutants were isolated at the all2 gene on the basis of their inability to utilize hypoxanthine as a sole source of nitrogen. These mutants failed to utilize the purines adenine, hypoxanthine, xanthine, uric acid, allantoin and allantoic acid, although they could utilize urea and ammonium. The all2 mutants appeared to be defective in purine induction of uricase, allantoinase, allantoicase and ureidoglycollase activities but retained wild-type activity of the constitutively synthesized urease. The all2 mutations were recessive. (+info)