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Leucine accelerates blood ethanol oxidation by enhancing the activity of ethanol metabolic enzymes in the livers of SHRSP rats

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Abstract

Chronic ethanol consumption induces liver diseases, such as alcoholic hepatitis and cirrhosis. The enhancement of alcohol oxidation is important in the prevention of these liver diseases. Chronic supplementation with branched chain amino acids (BCAAs) prevents liver cirrhosis. Therefore, BCAAs may be associated with enhanced ethanol oxidation. To evaluate this hypothesis, we investigated the effect of the administration of individual BCAAs on ethanol oxidation and changes in alcohol-metabolizing enzyme activities following acute alcohol intake in rats. Blood ethanol concentrations and the activities of alcohol-metabolizing enzymes, such as alcohol dehydrogenase (ADH) and low and high Km aldehyde dehydrogenase (ALDH), were measured in the liver following acute ethanol administration in rats; the ethanol was administered 30 min after the treatment with amino acids [such as leucine (Leu), isoleucine (Ile), valine (Val) or alanine (Ala)]. Leu significantly decreased the blood ethanol concentration 1 h after ethanol administration compared to the water-treated control (C) [C 0.46 ± 0.09, Leu 0.18 ± 0.04, Ile 0.27 ± 0.09, Val 0.46 ± 0.1, Ala 0.43 ± 0.06, mean ± SEM (g/l), P < 0.05]. In addition, leucine significantly stimulated ADH activity 30 min after ethanol intake [C 0.042 ± 0.014, Leu 0.090 ± 0.016, Ile 0.042 ± 0.008, Val 0.022 ± 0.010, Ala 0.070 ± 0.016, mean ± SEM (unit/mg protein), P < 0.05] and low Km ALDH activity 15 min after ethanol intake [C 0.51 ± 0.63, Leu 3.72 ± 0.66, Ile 1.26 ± 0.89, Val: ND, Ala 1.86 ± 1.57, mean ± SEM (unit/mg protein), P < 0.05]. However, leucine and its metabolite α-keto-isocaproic acid did not enhance ethanol clearance in isolated rat hepatocytes. These results indicate that leucine accelerates ethanol oxidation by indirectly enhancing ADH and low Km ALDH activities in the liver.

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Abbreviations

BCAAs:

Branched-chain amino acids

Leu:

Leucine

Ile:

Isoleucine

Val:

Valine

Ala:

Alanine

KIC:

α-Keto-isocaproic acid

KMV:

α-Keto-β-methyl valeric acid

ADH:

Alcohol dehydrogenase

ALDH:

Aldehyde dehydrogenase

GOT:

Glutamate oxaloacetate transaminase

IL-6:

Interleukin-6

TNF-α:

Tumor necrosis factor-α

mTOR:

Mammalian target of rapamycin

SHRSP:

Spontaneously hypertensive stroke prone

NAD:

Nicotinamide adenine dinucleotide

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Acknowledgments

We thank Dr. Hideyuki Sone, Mr. Osamu Fukaya and Mrs. Yumi Murakami for their assistance with the experimental trials.

Conflict of interest

The authors declare that they have no conflict of interest.

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Author notes

  1. Hitoshi Murakami

    Present address: Frontier Research Laboratories, Institute for Innovation, Ajinomoto Co., Inc., 1-1 Suzuki-cho, Kawasaki, 210-8681, Japan

Authors and Affiliations

  1. Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai, 981-8555, Japan

    Hitoshi Murakami, Michiko Ito, Yuji Furukawa & Michio Komai

Authors
  1. Hitoshi Murakami
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  2. Michiko Ito
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  3. Yuji Furukawa
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  4. Michio Komai
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Correspondence to Michio Komai.

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Murakami, H., Ito, M., Furukawa, Y. et al. Leucine accelerates blood ethanol oxidation by enhancing the activity of ethanol metabolic enzymes in the livers of SHRSP rats. Amino Acids 43, 2545–2551 (2012). https://doi.org/10.1007/s00726-012-1406-8

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  • DOI: https://doi.org/10.1007/s00726-012-1406-8

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