Role of Branched-Chain Aminotransferase Isoenzymes and Gabapentin in Neurotransmitter Metabolism

ABSTRACT In Lactococcus lactis, which is widely used as a starter in the cheese industry, the first step of aromatic and branched-chain amino acid degradation is a transamination which is catalyzed by two major aminotransferases. We have previously purified and characterized biochemically and genetically the aromatic aminotransferase, AraT. In the present study, we purified and studied the second enzyme, the branched-chain aminotransferase, BcaT. We cloned and sequenced the corresponding gene and used a mutant, along with the luciferase gene as the reporter, to study the role of the enzyme in amino acid metabolism and to reveal the regulation of gene transcription. BcaT catalyzes transamination of the three branched-chain amino acids and methionine and belongs to class IV of the pyridoxal 5′-phosphate-dependent aminotransferases. In contrast to most of the previously described bacterial BcaTs, which are hexameric, this enzyme is homodimeric. It is responsible for 90% of the total isoleucine and valine aminotransferase activity of the cell and for 50 and 40% of the activity towards leucine and methionine, respectively. The original role of BcaT was probably biosynthetic since expression of its gene was repressed by free amino acids and especially by isoleucine. However, in dairy strains, which are auxotrophic for branched-chain amino acids, BcaT functions only as a catabolic enzyme that initiates the conversion of major aroma precursors. Since this enzyme is still active under cheese-ripening conditions, it certainly plays a major role in cheese flavor development.

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Identification of the mitochondrial branched chain aminotransferase as a branched chain alpha-keto acid transport protein.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)53662-0 ◽

1993 ◽

Vol 268 (5) ◽

pp. 3084-3091 ◽

Cited By ~ 1

Author(s):

S.M. Hutson ◽

T.R. Hall

Keyword(s):

Transport Protein ◽

Keto Acid ◽

Acid Transport ◽

Branched Chain ◽

Branched Chain Aminotransferase

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The role of gut microbiota and amino metabolism in the effects of improvement of islet β-cell function after modified jejunoileal bypass

Scientific Reports ◽

10.1038/s41598-021-84355-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Cai Tan ◽

Zhihua Zheng ◽

Xiaogang Wan ◽

Jiaqing Cao ◽

Ran Wei ◽

...

Keyword(s):

Gut Microbiota ◽

Cell Function ◽

Body Weight Gain ◽

Fasting Blood Glucose ◽

Jejunoileal Bypass ◽

Β Cell ◽

Β Cell Function ◽

Branched Chain

AbstractThe change in gut microbiota is an important mechanism of the amelioration of type 2 diabetes mellitus (T2DM) after bariatric surgery. Here, we observe that the modified jejunoileal bypass effectively decreases body weight gain, fasting blood glucose, and lipids level in serum; additionally, islet β-cell function, glucose tolerance, and insulin resistance were markedly ameliorated. The hypoglycemic effect and the improvement in islet β-cell function depend on the changes in gut microbiota structure. modified jejunoileal bypass increases the abundance of gut Escherichia coli and Ruminococcus gnavus and the levels of serum glycine, histidine, and glutamine in T2DM rats; and decreases the abundance of Prevotella copri and the levels of serum branched chain amino acids, which are significantly related to the improvement of islet β-cell function in T2DM rats. Our results suggest that amino acid metabolism may contribute to the islet β-cell function in T2DM rats after modified jejunoileal bypass and that improving gut microbiota composition is a potential therapeutic strategy for T2DM.

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Impaired branched chain amino acid metabolism alters feeding behavior and increases orexigenic neuropeptide expression in the hypothalamus

Journal of Endocrinology ◽

10.1530/joe-11-0270 ◽

2011 ◽

Vol 212 (1) ◽

pp. 85-94 ◽

Cited By ~ 14

Author(s):

Megan N Purpera ◽

Li Shen ◽

Marzieh Taghavi ◽

Heike Münzberg ◽

Roy J Martin ◽

...

Keyword(s):

Amino Acid ◽

Food Intake ◽

Feeding Behavior ◽

Control Diet ◽

Peripheral Tissues ◽

Protein Status ◽

Branched Chain Amino Acid ◽

Branched Chain ◽

Branched Chain Aminotransferase ◽

Deficient Mice

Elevation of dietary or brain leucine appears to suppress food intake via a mechanism involving mechanistic target of rapamycin, AMPK, and/or branched chain amino acid (BCAA) metabolism. Mice bearing a deletion of mitochondrial branched chain aminotransferase (BCATm), which is expressed in peripheral tissues (muscle) and brain glia, exhibit marked increases in circulating BCAAs. Here, we test whether this increase alters feeding behavior and brain neuropeptide expression. Circulating and brain levels of BCAAs were increased two- to four-fold in BCATm-deficient mice (KO). KO mice weighed less than controls (25.9 vs 20.4 g,P<0.01), but absolute food intake was relatively unchanged. In contrast to wild-type mice, KO mice preferred a low-BCAA diet to a control diet (P<0.05) but exhibited no change in preference for low- vs high-protein (HP) diets. KO mice also exhibited low leptin levels and increased hypothalamicNpyandAgrpmRNA. Normalization of circulating leptin levels had no effect on either food preference or the increasedNpyandAgrpmRNA expression. If BCAAs act as signals of protein status, one would expect reduced food intake, avoidance of dietary protein, and reduction in neuropeptide expression in BCATm-KO mice. Instead, these mice exhibit an increased expression of orexigenic neuropeptides and an avoidance of BCAAs but not HP. These data thus suggest that either BCAAs do not act as physiological signals of protein status or the loss of BCAA metabolism within brain glia impairs the detection of protein balance.

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Plasma Branched-Chain Amino Acids and Incident Cardiovascular Disease in the PREDIMED Trial

Clinical Chemistry ◽

10.1373/clinchem.2015.251710 ◽

2016 ◽

Vol 62 (4) ◽

pp. 582-592 ◽

Cited By ~ 91

Author(s):

Miguel Ruiz-Canela ◽

Estefania Toledo ◽

Clary B Clish ◽

Adela Hruby ◽

Liming Liang ◽

...

Keyword(s):

Cardiovascular Disease ◽

Amino Acids ◽

Cardiovascular Death ◽

Branched Chain Amino Acids ◽

Control Group ◽

Cvd Risk ◽

Hazard Ratios ◽

Increased Risk ◽

Branched Chain

Abstract BACKGROUND The role of branched-chain amino acids (BCAAs) in cardiovascular disease (CVD) remains poorly understood. We hypothesized that baseline BCAA concentrations predict future risk of CVD and that a Mediterranean diet (MedDiet) intervention may counteract this effect. METHODS We developed a case-cohort study within the Prevención con Dieta Mediterránea (PREDIMED), with 226 incident CVD cases and 744 noncases. We used LC-MS/MS to measure plasma BCAAs (leucine, isoleucine, and valine), both at baseline and after 1 year of follow-up. The primary outcome was a composite of incident stroke, myocardial infarction, or cardiovascular death. RESULTS After adjustment for potential confounders, baseline leucine and isoleucine concentrations were associated with higher CVD risk: the hazard ratios (HRs) for the highest vs lowest quartile were 1.70 (95% CI, 1.05–2.76) and 2.09 (1.27–3.44), respectively. Stronger associations were found for stroke. For both CVD and stroke, we found higher HRs across successive quartiles of BCAAs in the control group than in the MedDiet groups. With stroke as the outcome, a significant interaction (P = 0.009) between baseline BCAA score and intervention with MedDiet was observed. No significant effect of the intervention on 1-year changes in BCAAs or any association between 1-year changes in BCAAs and CVD were observed. CONCLUSIONS Higher concentrations of baseline BCAAs were associated with increased risk of CVD, especially stroke, in a high cardiovascular risk population. A Mediterranean-style diet had a negligible effect on 1-year changes in BCAAs, but it may counteract the harmful effects of BCAAs on stroke.

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