Assignment of the human pyruvate carboxylase gene (PC) to 11q13.4 by fluorescence in situ hybridisation

Pyruvate carboxylase (PC; EC 6.4.1.1), a member of the biotin-dependent enzyme family, catalyses the ATP-dependent carboxylation of pyruvate to oxaloacetate. PC has been found in a wide variety of prokaryotes and eukaryotes. In mammals, PC plays a crucial role in gluconeogenesis and lipogenesis, in the biosynthesis of neurotransmitter substances, and in glucose-induced insulin secretion by pancreatic islets. The reaction catalysed by PC and the physical properties of the enzyme have been studied extensively. Although no high-resolution three-dimensional structure has yet been determined by X-ray crystallography, structural studies of PC have been conducted by electron microscopy, by limited proteolysis, and by cloning and sequencing of genes and cDNA encoding the enzyme. Most well characterized forms of active PC consist of four identical subunits arranged in a tetrahedron-like structure. Each subunit contains three functional domains: the biotin carboxylation domain, the transcarboxylation domain and the biotin carboxyl carrier domain. Different physiological conditions, including diabetes, hyperthyroidism, genetic obesity and postnatal development, increase the level of PC expression through transcriptional and translational mechanisms, whereas insulin inhibits PC expression. Glucocorticoids, glucagon and catecholamines cause an increase in PC activity or in the rate of pyruvate carboxylation in the short term. Molecular defects of PC in humans have recently been associated with four point mutations within the structural region of the PC gene, namely Val145 → Ala, Arg451 → Cys, Ala610 → Thr and Met743 → Thr.

show abstract

“…5h-UTR, 5h-untranslated region exon. [170]. The human PC gene also contains 19 coding exons, spanning over 16 kb [171] (Figure 4).…”

Section: Figure 4 Structural Organization Of Mammalian Pc Genes and Pmentioning

confidence: 99%

Structure, function and regulation of pyruvate carboxylase

Jitrapakdee

Wallace

1999

Biochemical Journal

183

View full text Add to dashboard Cite

show abstract

“…In the yeast Saccharomyces cerevisiae, there are two genes encoding two isoenzymes, PC1 and PC2, which are differentially expressed (18). Unlike yeast, only one gene has been identified in rat (17), mouse (19), and human (20). However, the genomic organization of PC in these organisms has not been reported.…”

mentioning

confidence: 99%

The Rat Pyruvate Carboxylase Gene Structure

Jitrapakdee¹,

Booker²,

Cassady³

et al. 1997

Journal of Biological Chemistry

View full text Add to dashboard Cite

“…In mouse, rat, and human, PC is encoded by a single copy, nuclear gene (Walker et al, 1995;Webb et al, 1997;Jitrapakdee et al, 2001). Alternative transcription from two alternative promoters, the proximal and distal promoters, produces mRNA isoforms which differ in their 5 0 -untranslated regions (UTR) but have identical coding sequences.…”

Section: Pyruvate Carboxylasementioning

confidence: 99%