TY - JOUR
T1 - Impaired homocysteine transsulfuration is an indicator of alcoholic liver disease
AU - Medici, Valentina
AU - Peerson, Janet M.
AU - Stabler, Sally P.
AU - French, Samuel W.
AU - Gregory, Jesse F.
AU - Virata, Maria Catrina
AU - Albanese, Antony
AU - Bowlus, Christopher
AU - Devaraj, Sridevi
AU - Panacek, Edward A
AU - Rahim, Nazir
AU - Richards, John R
AU - Rossaro, Lorenzo
AU - Halsted, Charles H.
PY - 2010/9
Y1 - 2010/9
N2 - Background & Aims: Although abnormal hepatic methionine metabolism plays a central role in the pathogenesis of experimental alcoholic liver disease (ALD), its relationship to the risk and severity of clinical ALD is not known. The aim of this clinical study was to determine the relationship between serum levels of methionine metabolites in chronic alcoholics and the risk and pathological severity of ALD. Methods: Serum levels of liver function biochemical markers, vitamin B6, vitamin B12, folate, homocysteine, methionine, S-adenosylmethionine, S-adenosylhomocysteine, cystathionine, cysteine, α-aminobutyrate, glycine, serine, and dimethylglycine were measured in 40 ALD patients, of whom 24 had liver biopsies, 26 were active drinkers without liver disease, and 28 were healthy subjects. Results: Serum homocysteine was elevated in all alcoholics, whereas ALD patients had low vitamin B6 with elevated cystathionine and decreased α-aminobutyrate/cystathionine ratios, consistent with decreased activity of vitamin B6 dependent cystathionase. The α-aminobutyrate/cystathionine ratio predicted the presence of ALD, while cystathionine correlated with the stage of fibrosis in all ALD patients. Conclusions: The predictive role of the α-aminobutyrate/cystathionine ratio for the presence of ALD and the correlation between cystathionine serum levels with the severity of fibrosis point to the importance of the homocysteine transsulfuration pathway in ALD and may have important diagnostic and therapeutic implications.
AB - Background & Aims: Although abnormal hepatic methionine metabolism plays a central role in the pathogenesis of experimental alcoholic liver disease (ALD), its relationship to the risk and severity of clinical ALD is not known. The aim of this clinical study was to determine the relationship between serum levels of methionine metabolites in chronic alcoholics and the risk and pathological severity of ALD. Methods: Serum levels of liver function biochemical markers, vitamin B6, vitamin B12, folate, homocysteine, methionine, S-adenosylmethionine, S-adenosylhomocysteine, cystathionine, cysteine, α-aminobutyrate, glycine, serine, and dimethylglycine were measured in 40 ALD patients, of whom 24 had liver biopsies, 26 were active drinkers without liver disease, and 28 were healthy subjects. Results: Serum homocysteine was elevated in all alcoholics, whereas ALD patients had low vitamin B6 with elevated cystathionine and decreased α-aminobutyrate/cystathionine ratios, consistent with decreased activity of vitamin B6 dependent cystathionase. The α-aminobutyrate/cystathionine ratio predicted the presence of ALD, while cystathionine correlated with the stage of fibrosis in all ALD patients. Conclusions: The predictive role of the α-aminobutyrate/cystathionine ratio for the presence of ALD and the correlation between cystathionine serum levels with the severity of fibrosis point to the importance of the homocysteine transsulfuration pathway in ALD and may have important diagnostic and therapeutic implications.
KW - Alcohol
KW - Cystathionine
KW - Methionine
KW - Vitamin B6
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U2 - 10.1016/j.jhep.2010.03.029
DO - 10.1016/j.jhep.2010.03.029
M3 - Article
C2 - 20561703
AN - SCOPUS:77955849533
VL - 53
SP - 551
EP - 557
JO - Journal of Hepatology
JF - Journal of Hepatology
SN - 0168-8278
IS - 3
ER -