Disease relevance of CRAT

• This study was designed to evaluate the effect of severe peripheral arterial insufficiency on carnitine concentrations and carnitine acetyltransferase and palmitoyltransferase activities in the ischemic skeletal muscles of patients with severe peripheral vascular disease [1].
• The high activity of carnitine acetyltransferase in human liver is consistent with the observation that acetylcarnitine is the predominant acylcarnitine excreted in diabetic ketosis in man [2].
• Muscle carnitine acetyltransferase and carnitine deficiency in a case of mitochondrial encephalomyopathy [3].
• In vitro perfluorodecanoate (PFDA) effects on Pseudomonas acyl-CoA synthetase, Candida acyl-CoA oxidase and pigeon muscle carnitine acetyltransferase were examined [4].
• We report evidence in support of a notion that Cat1 as well as a tetrazolium salt, CTC (5-cyano-2,3-ditolyl tetrazolium chloride), are reduced extracellularly, probably at the cell surface, by human HepG2 hepatoma cells [5].

Psychiatry related information on CRAT

• We found a 25 to 40% decrease in carnitine acetyltransferase activity in patients with Alzheimer's disease, which attained statistical significance in most brain regions and in cerebral microvessels [6].

High impact information on CRAT

• The recent colocalization of the cationic amino acid transporter CAT-1 (system y(+)), nitric oxide synthase (eNOS), and caveolin-1 in endothelial plasmalemmal caveolae provides a novel mechanism for the regulation of NO production by L-arginine delivery and circulating hormones such insulin and 17beta-estradiol [7].
• In the CAT family, three genes encode for four different isoforms [CAT-1, CAT-2A, CAT-2(B) and CAT-3]; these are approximately 70-kDa proteins with multiple transmembrane segments (12-14), and despite their structural similarity, they differ in tissue distribution, kinetics, and regulatory properties [8].
• Carnitine acetyltransferase and carnitine octanoyltransferase are also found in the peroxisomes [9].
• We report the crystal structures of murine carnitine acetyltransferase (CRAT), alone and in complex with its substrate carnitine or CoA [10].
• The substrate specificity of the carnitine acetyltransferase enzyme and its steady state nature appears to facilitate elimination of propionyl groups while restoring the acyl-CoA:free CoA ratio in the mitochondrion [11].

Chemical compound and disease context of CRAT

• In vivo and in vitro measures of L-arginine transport were substantially reduced in the essential hypertension and positive family history groups compared with the negative family history group; however, no difference was detected in peripheral blood mononuclear cell mRNA or protein expression levels for the cationic amino acid transporter CAT-1 [12].
• The weight gain was supported by increases in the levels of glucose 6-phosphate dehydrogenase, L-alanine aminotransferase and carnitine acetyltransferase in the liver [13].

Biological context of CRAT

• Data from the human genome sequencing efforts now reveal drafts of the genomic structure of CPT1A and CRAT, the latter not being known from any other mammal [14].
• We identified two partially overlapping cDNAs containing divergent 5' sequences of human carnitine acetyltransferase (CAT). cDNA lambda SM-1400 extends the sequence of peroxisomal CAT, whereas cDNA lambda SM-1200 creates a new open reading frame encoding a putative mitochondrial leader peptide [15].
• L-carnitine binds to a preformed pocket in the active site tunnel of carnitine acetyltransferase aligned with His(322) [16].
• Molecular cloning of cDNAs encoding human carnitine acetyltransferase and mapping of the corresponding gene to chromosome 9q34.1 [17].
• Using a combination of PCR screening of cDNA libraries and reverse transcription PCR, we have cloned three overlapping DNA fragments that encode human carnitine acetyltransferase (CAT), a key enzyme for metabolic pathways involved with the control of the acyl-CoA/CoA ratio in mitochondria, peroxisomes, and endoplasmic reticulum [17].

Anatomical context of CRAT

• In MDS bone marrow cells there was a negative correlation of CPT1 and CRAT with the relative proportion of apoptotic cells [18].
• We evaluated the activities of carnitine palmitoyltransferase (CPT), carnitine octanoyltransferase (COT), and carnitine acetyltransferase (CAT) in the frontal cortex, temporal cortex, parietal cortex, hippocampus, and cerebellum of Alzheimer disease (AD) patients and normal human brains [19].
• Immunoprecipitation experiments of in vitro translation products suggest that this element has an effect on the level of translatable Cat1 mRNA associated with the scutellar polysomes [20].
• In cultured hepatocytes, ciprofibrate was about 30-fold more active than clofibric acid for the stimulation of carnitine acetyltransferase, laurate hydroxylase and fatty acylCoA oxidase activities [21].
• Carnitine acetyltransferase was deficient in liver, brain, kidney, and cultured fibroblasts [22].

Associations of CRAT with chemical compounds

• We have determined the crystal structures of murine CrAT, alone and in complex with its substrate carnitine or CoA [23].
• Other malonyl-CoA non-inhibitable members of the family, CPT II and carnitine acetyltransferase, do not contain this domain [24].
• In this single-tube reaction system palmitoylcarnitine is converted by CPT-II to free carnitine, which is subsequently esterified to acetylcarnitine by carnitine acetyltransferase [25].
• Carnitine palmitoyltransferase II and palmitoyl-CoA synthetase activities were increased, whereas carnitine acetyltransferase, glycerol-3-phosphate dehydrogenase (FAD) and succinate dehydrogenase were decreased [26].
• Carnitine acetyltransferase catalyzes the interchange between L-carnitine and acetyl-L-carnitine [6].

Other interactions of CRAT

• Reduction in CRAT, CPT 2, and OCTN2 was more than 85% [18].
• Titration of carnitine acetyltransferase with nonspecific sulfhydryl reagents, DTNB, and rho-nitrophenoxycarbonyl methyl disulfide, revealed that four sulfhydryl groups were preferentially modified by these reagents [27].
• Hexokinase, carnitine acetyltransferase and citrate synthase levels were similar in the testes of hibernating and aroused males [13].
• The response includes a marked proliferation of peroxisomes and enhanced activity of peroxisomal enzymes enoyl-CoA hydratase (8.5- to 13-fold), [1-14C]-palmitoyl-CoA oxidation (2.8- to 3.9-fold), catalase (1.6 to 3.4-fold), and carnitine acetyltransferase (greater than 2,000-fold) [28].
• Cat1 encodes CAT-1 catalase, one of two forms of catalase expressed in the scutellum during this developmental time period [20].

Analytical, diagnostic and therapeutic context of CRAT

• CAT cDNA has also been used for fluorescence in situ hybridization on metaphase spreads of human chromosomes, and the corresponding gene, CAT1, has been mapped to chromosome 9q34.1 [17].
• In this paper, the purification, crystallization and preliminary X-ray crystallographic studies of human carnitine acetyltransferase are reported [29].
• Western blotting data showed that hCAT-1 protein expression in PE BM was higher than that in CBM [30].
• Semiquantitative RT-PCR analysis showed that the levels of mRNAs for both CAT-1 and CAT-2B were significantly higher at midnight than at midday [31].
• In northern blotting using the cDNA-specific probe, the cat1 mRNA levels were high in seeds and early seedlings of pumpkin [32].

References