PPA1 (Inorganic pyrophosphatase 1, also PPase and IOPPP) is a 32-36 kDa cytoplasmic member of the PPase family of enzymes. It is ubiquitously expressed, and acts on di-(or pyro) phosphate, generating orthophosphate in a Mg+-dependent manner. This activity can both generate energy for cells, or in the case of osteoblasts, provide raw material for calcification. The consumption of pyrophosphate may also remove inhibitors of enzymes such as guanylyl cyclase, and PPA1 itself is also reported to stimulate gene expression. Human PPA1 is 289 amino acids (aa) in length. There is one pyrophosphatase domain between aa 42-255, and two utilized acetylation sites at Lys 57 and Lys228. PPA1 is known to form homodimers. There is one potential alternative start site at Met46. Full-length human PPA1 shares 94% aa sequence identity with mouse PPA1.
Ligand-activated transcription factor key mediator of energy metabolism in adipose tissues.Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Has a preference for poly-unsaturated fatty acids, such as gamma-linoleic acid and eicosapentanoic acid. Once activated by a ligand, the receptor binds to promoter elements of target genes. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the acyl-CoA oxidase gene. Decreases expression of NPC1L1 once activated by a ligand
Involved in the biosynthesis of tetrahydrobiopterin, an essential cofactor of aromatic amino acid hydroxylases. Catalyzes the transformation of 7,8-dihydroneopterin triphosphate into 6-pyruvoyl tetrahydropterin.
Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated pro-inflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of ARNTL/BMAL1 in the blood vessels.
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