Disease relevance of C01181

• Forty-one aromatic and aliphatic analogs of alpha-ketoglutarate were studied kinetically for their interaction with the alpha-ketoglutarate binding site of gamma-butyrobetaine hydroxylase obtained from Pseudomonas sp. AK1 [1].
• Transport of gamma-butyrobetaine in an Agrobacterium species isolated from soil [2].
• Contrary to other Enterobacteriaceae no reduction of crotonobetaine into gamma-butyrobetaine could be detected in the culture supernatants [3].
• Effect of gamma-butyrobetaine on fatty liver in juvenile visceral steatosis mice [4].
• Mildronate, an inhibitor of carnitine biosynthesis, induces an increase in gamma-butyrobetaine contents and cardioprotection in isolated rat heart infarction [5].

High impact information on C01181

• Characterization of a sodium-dependent transport system for butyrobetaine into rat liver plasma membrane vesicles [6].
• Butyrobetaine transport activity was also expressed in Xenopus laevis oocytes by injecting mRNA isolated from rat liver or kidney [6].
• Butyrobetaine transport into the liver was studied using isolated rat hepatocyte plasma membrane vesicles [6].
• Taken together, the results suggest that CaiT functions as an exchanger (antiporter) for l-carnitine and gamma-butyrobetaine according to the substrate/product antiport principle [7].
• This is of particular interest since the delineated stereochemical mode of oxidative decarboxylation could generate the reactive oxo-iron species that was shown experimentally to promote gamma-butyrobetaine hydroxylation by an abstraction-recombination mechanism (Blanchard, J [1].

Chemical compound and disease context of C01181

• Primary and secondary tritium kinetic isotope effects have been determined for the reactions catalyzed by purified preparations of gamma-butyrobetaine hydroxylase obtained from Pseudomonas sp AK 1 and from calf liver [8].
• Finally, various members of the Enterobacteriaceae are able to convert carnitine, via crotonobetaine, to gamma-butyrobetaine in the presence of C and N sources and under anaerobic conditions [9].
• Conversion of gamma-butyrobetaine to L-carnitine by Achromobacter cycloclast [10].

Biological context of C01181

• Omission of potassium decreased the apparent maximum velocity of decarboxylation supported by all three compounds by a similar percent. beta-Bromo-alpha-ketoglutarate supported gamma-butyrobetaine hydroxylation, although less effectively than alpha-ketoglutarate [11].
• This suggests a transport mechanism involving a periplasmic gamma-butyrobetaine binding protein [2].
• The methylester of gamma-butyrobetaine, but not gamma-butyrobetaine itself, induces muscarinic receptor-dependent vasodilatation [12].
• Beneficial effect of MET-88, a gamma-butyrobetaine hydroxylase inhibitor, on energy metabolism in ischemic dog hearts [13].
• Two-stage culture results showed that gamma-butyrobetaine induced enzymes essential for the conversion, which suggests that the precursor should be present in the initial cell growth stage [10].

Anatomical context of C01181

• Starvation for 48 h did not affect the gamma-butyrobetaine concentration in serum, liver and brain, but that in skeletal muscles, kidney and heart was increased [14].
• Urine and feces of rats receiving oral L-[methyl-14C]carnitine consistently contained two radiolabeled metabolites which were identified as trimethylamine N-oxide (primarily in urine) and gamma-butyrobetaine (primarily in feces) [15].
• In particular, evidence demonstrating a bidirectional exchange between carnitine and deoxycarnitine across cardiac sarcolemma have been provided both in vitro and in vivo experiments [16].

Associations of C01181 with other chemical compounds

• Significant amounts of radioactivity are recovered in both carnitine and butyrobetaine of hepatic tissue after longer time periods, while the level of labeled trimethyllysine in this organ remains very low [17].
• The observed high affinity of gamma-butyrobetaine hydroxylase for gamma-butyrobetaine (Km 7 microM), the high activity of this enzyme and the low concentration of gamma-butyrobetaine in liver indicate that gamma-butyrobetaine availability is one of the factors that normally limit carnitine synthesis [14].
• In contrast, concentrations up to 12.5 mM of dimethylcarnitine, deoxycarnitine, acetylcholine, acetyl-beta-methylcholine, or inositol had no detectable inhibitory effect on aggregation elicited by clusterin [18].
• Derivatization of isolated endogenous butyrobetaine with 4'-bromophenacyl trifluoromethanesulfonate followed by high-performance liquid chromatography [19].
• Intermediates of L(-)-carnitine metabolism (crotonobetaine, gamma-butyrobetaine) could be detected by thin-layer chromatography [20].

Gene context of C01181

• The stereochemical course of the aliphatic hydroxylation of gamma-butyrobetaine by calf liver and by Pseudomonas sp AK1 gamma-butyrobetaine hydroxylases has been determined [21].
• gamma-Butyrobetaine hydroxylase: a unique protective effect of catalase [22].
• Mildronate (3-(2,2,2,-trimethylhydrazinium)propionate), is a butyrobetaine analogue that is known to inhibit gamma-butyrobetaine hydroxylase, the enzyme catalyzing the last step of carnitine biosynthesis [23].
• The latter are potent cholinomimetics and may activate eNOS via acetylcholine receptors or specific gamma-butyrobetaine ester receptors [24].
• The uptake of radiolabeled carnitine and butyrobetaine has been studied in human heart cells (CCL 27) [25].

Analytical, diagnostic and therapeutic context of C01181

• A binding protein for gamma-butyrobetaine was purified from osmotic shock fluid of an Agrobacterium sp. It was a monomeric protein with an apparent molecular weight of 52,000 or 53,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration, respectively [26].
• The HPLC detection sensitivity to butyrobetaine 4'-bromophenacyl ester was 1 pmol injected with a signal-to-noise greater than 2:1 [19].
• The reaction product, gamma-butyrobetaine, was identified by autoradiography [27].

References