Disease relevance of Crat

• Clofibrate-treatment increases hepatic CoA content and carnitine acetyltransferase activity, both of which may modulate propionate toxicity [1].
• Five daily oral doses of di(2-ethylhexyl) phthalate (DEHP) (2 g/kg) given to rats on Days 2-6, 6-10, or 14-18 of lactation caused significant decreases in body weight and increases in hepatic peroxisomal enzymes palmitoyl CoA oxidase and carnitine acetyltransferase in the dams and their suckling pups [2].
• In the rat, hepatomegaly was observed with the coordinate induction of carnitine acetyltransferase, peroxisomal beta-oxidation and cytochrome P450IVA1 activities [3].
• Cholestasis reduced the activity of carnitine acetyltransferase, carnitine octanoyltransferase, and carnitine palmitoyltransferase to 66 +/- 2%, 64 +/- 3%, and 40 +/- 2%, of the control, respectively [4].
• In contrast, cyanide-insensitive peroxisomal beta-oxidation and the carnitine acetyltransferase and catalase activities associated with the peroxisomal-enriched fraction were markedly reduced by abdominal sepsis [5].

High impact information on Crat

• We have also demonstrated the presence of carnitine acetyltransferase in intestinal mucosa and have shown that the intestine forms significant amounts of acetylcarnitine from exogenous carnitine [6].
• The time course of increase in catalase and carnitine acetyltransferase activities correlated with the morphometric data on the peroxisomes [7].
• Age-associated mitochondrial oxidative decay: improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-L- carnitine and/or R-alpha -lipoic acid [8].
• Acetylation of added (-)carnitine by heart mitochondira coupled to the oxidation of pyruvate in the presence of malonate was inhibited, apparently competitively, by long chain acyl(+)carnitines although the activity of carnitine acetyltransferase (EC 2.3.1.7) itself was not affected [9].
• The M564G mutated CrAT showed higher activity toward longer chain acyl-CoAs: activity toward myristoyl-CoA was 1250-fold higher than that of the wild-type CrAT, and lower activity toward its natural substrate, acetyl-CoA [10].

Chemical compound and disease context of Crat

• 1) Vitamin B2-butyrate (100 mg/kg) and nicomol (lg/Kg) increased carnitine acetyltransferase and D-amino acid oxidase activities, respectively, while these drugs had no influence on body weight, liver weight, serum and liver triglyceride, and serum and liver cholesterol levels [11].

Biological context of Crat

• We show for the first time that a single amino acid is able to determine the substrate specificity of CrAT and COT [10].
• We conclude that Met564 blocks the entry of medium- and long-chain acyl-CoAs to the catalytic site of CrAT [10].
• Mutations F487S and positional swap F487S/S488F produced pumps that were severely defective in ATP binding (KD > 1 mM), and mutant F487S, together with F487E, exhibited low ATPase activity and low ATP-supported calcium transport and phosphorylation and failed to show CrATP-dependent Ca2+ occlusion [12].
• Cell fractionation studies suggested that the cardiac carnitine binding protein was associated with the plasma membrane fraction and that its activity was distinct from carnitine palmitoyl-transferase, carnitine acetyltransferase, and carnitine translocase [13].
• Mutagenesis of specific amino acids converts carnitine acetyltransferase into carnitine palmitoyltransferase [14].

Anatomical context of Crat

• Carnitine acetyltransferase activities of intact mitochondria from a YAT1 deletion mutant are slightly lower than wild type, but are approximately alike in lysed mitochondria from mutant and control cells [15].
• Palmitoyl CoA oxidase and carnitine acetyltransferase activities in isolated hepatocytes were elevated by WY-14,643 (50 mg/kg/day by gavage for up to 5 consecutive days) and by WY-14,643 (0.1%) or di(2-ethyl-hexyl)phthalate (DEHP) (1.2%) feeding (for up to 28 days), indicating peroxisome proliferation had occurred [16].
• The activities of pyruvate dehydrogenase, citrate synthase, acetyl-CoA synthase, and carnitine acetyltransferase in crude hippocampal homogenates and in subcellular fractions were not affected by septal lesions [17].
• NADP+-malate dehydrogenase, mitochondrial glycerol 3-phosphate dehydrogenase, succinate dehydrogenase, carnitine acetyltransferase and citrate synthase were 5 to 400 times as active in spermatozoa as in epididymal tissue [18].
• Absence of increased carnitine acetyltransferase activity in the liver with proliferation of smooth endoplasmic reticulum [19].

Associations of Crat with chemical compounds

• Carnitine acetyltransferases (CrAT) catalyze the reversible conversion of acetyl-CoA and carnitine to acetylcarnitine and free CoA [10].
• These data indicate that peroxisomal carnitine octanoyltransferase and carnitine acetyltransferase function in vivo in the direction of acylcarnitine formation, and suggest that the concentration of L-carnitine could influence the specificity for different acyl-CoA substrates [20].
• 5. Neither carnitine octanoyltransferase nor carnitine acetyltransferase were inhibited by malonyl-CoA [20].
• As anticipated from the low group transfer potential of amides, carnitine acetyltransferase catalyzes the transfer of acetyl groups from CoASAc to aminocarnitine (Km = 3.8 mM) but does not catalyze detectable transfer from acetylaminocarnitine to CoASH [21].
• Free CoASH is also regenerated from S-acetyl-3-mercaptopropionyl-CoA and more rapidly from 3-mercaptopropionyl-CoA as a result of their reactions with carnitine catalyzed by carnitine acetyltransferase [22].

Regulatory relationships of Crat

• Treatment of 7800C1 cells with 100 microM all-trans-retinoic acid resulted in inductions of catalase (160% above the control activity) and carnitine acetyltransferase (140% above the control activity) activities [23].

Other interactions of Crat

• Total carnitine acetyltransferase and butyrylcholinesterase activities were markedly decreased [24].
• This thioether-containing structural analogue of acetyl-CoA is a potent competitive inhibitor, with respect to acetyl-CoA, of citrate synthase, phosphotransacetylase, and carnitine acetyltransferase [25].
• The carnitine acylcarnitine translocase activity is unlikely to be shared by one of the carnitine acyltransferases because the mersalyl inhibition of carnitine palmitoyltransferase and carnitine acetyltransferase was noncompetitivcase [26].
• The effect of the lesion separated the enzymes into two groups: the activities of pyruvate dehydrogenase complex, carnitine acetyltransferase, fumarase and aspartate transaminase decreased by 30--40%, whereas the activities of the other enzymes descreased 5--15% [27].
• DEHP produced a thyromimetic effect, inducing the activity of malic enzyme and carnitine acetyltransferase in the absence of thyroid hormones [28].

Analytical, diagnostic and therapeutic context of Crat

• Redesign of carnitine acetyltransferase specificity by protein engineering [10].
• The transcription rate of CPT1, CPT2, and carnitine acetyltransferase (CRAT) was determined by quantitative reverse transcription real-time PCR (RTQPCR) and compared to the activity of the CPT1A enzyme [29].
• Liver peroxisomes, mitochondria, and microsomes and heart mitochondria all give multiple bands on Western blotting with the antibody against carnitine acetyltransferase [30].
• The two enzymes responsible for these processes, choline acetyltransferase and carnitine acetyltransferase, are shown to behave differently following denervation of the glands and bladders [31].
• The molecular weight of heart mitochondrial carnitine acetyltransferase, determined by SDS-PAGE, is 62,000 [30].

References