Disease relevance of Ppat

• The behavior of glutamine-phosphoribosylpyrophosphate amidotransferase (amidophosphoribosyltransferase, EC 2.4.2.14) was determined in normal, differentiating, and regenerating liver and in a spectrum of hepatomas of widely different growth rates [1].
• Hyperthyroidism significantly decreases activities of both microsomal acyl-CoA:glycero-3-phosphate acyltransferase (GPAT) (34%, p less than 0.01) and microsomal acyl-CoA:1-acylglycero-3-phosphocholine acyltransferase (GPCAT) (28-33%, p less than 0.01) [2].
• In contrast, hypothyroidism stimulates mitochondrial GPAT (38%, p less than 0.01) and microsomal GPCAT (14-19%) activities but decreases both mitochondrial phospholipase A2 (36%, p less than 0.01) and cytosol lysophospholipase (56%, p less than 0.01) activities [2].

High impact information on Ppat

• Purification, properties, and immunotitration of hepatoma glutamine phosphoribosylpyrophosphate amidotransferase (amidophosphoribosyltransferase, EC 2.4.2.14) [3].
• In addition, the activity of sn-glycerol-3-phosphate acyltransferase (GPAT), which like MCD and ACC can be regulated by AMP-activated protein kinase (AMPK), was assayed [4].
• Thirty min after the completion of a treadmill run, MCD activity was increased approximately 2-fold, malonyl-CoA levels were reduced, and ACC and GPAT activities were diminished by 50% in muscle and liver [4].
• An unexpected finding was that exercise caused similar changes in the activities of ACC, MCD, GPAT, and AMPK and the concentration of malonyl-CoA in adipose tissue [4].
• Based on these data, we propose a GPAT topography model with two transmembrane domains in which both the N (aa 1-471) and C (aa 593-end) termini face the cytosol and a single loop (aa 494-575) faces the intermembrane space [5].

Chemical compound and disease context of Ppat

• Imbalance of purine metabolism in hepatomas of different growth rates as expressed in behavior of glutamine-phosphoribosylpyrophosphate amidotransferase (amidophosphoribosyltransferase, EC 2.4.2.14) [1].

Biological context of Ppat

• A 6-8-fold increase in GPAT-specific activity in the transfected cells confirmed correct protein folding and orientation [5].
• Gene expression of sn-glycerol-3-phosphate acyltransferase (GPAT), diacylglycerol acyltransferase (DGAT), and hormone-sensitive lipase (HSL), three key enzymes of lipid metabolism, was detected in isolated rat islets [6].
• Norepinephrine-stimulated glycerol release from perigenital adipocytes was inhibited, whereas activities of esterification enzymes (GPAT and PPH) was essentially unaffected [7].

Anatomical context of Ppat

• Protease treatment of rat liver mitochondria revealed that GPAT has a membrane-protected segment of 14 kDa that could correspond to the mass of the two predicted TMDs plus a loop between aa 494 and 575 [5].
• When the C terminus and loop-tagged GPAT construct was immunoassayed, the epitope at the C terminus could be detected when the plasma membrane was permeabilized, but loop-epitope accessibility required disruption of the outer mitochondrial membrane [5].
• The topography of mitochondrial glycerol-3-phosphate acyltransferase (GPAT) was determined using rat liver mitochondria and mutagenized recombinant rat GPAT (828 aa (amino acids)) expressed in CHO cells [5].
• Overexpression of mitochondrial GPAT in rat hepatocytes leads to decreased fatty acid oxidation and increased glycerolipid biosynthesis [8].
• 2. GPAT activity in mitochondria differed from the microsomal activity in that it was insensitive to N-ethylmaleimide, had a higher affinity towards the palmitoyl-CoA substrate and showed a different response to changes in hormonal and dietary status [9].

Associations of Ppat with chemical compounds

• 1. GPAT (glycerol phosphate acyltransferase) and DHAPAT (dihydroxyacetone phosphate acyltransferase) activities were measured both in subcellular fractions prepared from fed rat liver and in whole homogenates prepared from freeze-stopped pieces of liver [9].
• Measurements were made of the activity of phosphoribosyl pyrophosphate amidotransferase (PPRibP-At, EC 2.4.2.14) and of adenine (APRT, EC 2.4.2.7) and hypoxanthine (HPRT, EC 2.4.2.8) phosphoribosyltransferases, representing the 'de novo' and salvage pathways respectively [10].
• Dihydroxyacetone phosphate acyl transferase (DHAP-AT), alkyl dihydroxyacetone phosphate synthase (alkyl-DHAP-synthase), and glycerol-3-phosphate acyltransferase (GPAT) activities were investigated under optimal assay conditions using highly purified organelle preparations [11].
• Methoxamine, an alpha 1-agonist, had no effect on TGL activity but reduced GPAT activity [12].
• Continuous perfusion of the beta-antagonist atenolol reduced TGL activity to half that found in controls but also reduced GPAT activity [12].

Analytical, diagnostic and therapeutic context of Ppat

• Mitochondrial GPAT activity was decreased by adrenalectomy in both fed and starved animals [9].
• However, GPAT activity, after 1 min of reperfusion, fell to a value lower than after 10 min ischaemia [13].

References