Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, NY 10029, USA. Electronic address: . Clinics in liver disease
(Impact Factor: 3.66).
11/2012; 16(4):667-85. DOI: 10.1016/j.cld.2012.08.002
This article describes the pathways and factors that modulate blood alcohol levels and metabolism and describes how the body disposes of alcohol. The various factors that play a role in the distribution of alcohol in the body, influence the absorption of alcohol, and contribute to first-pass metabolism of alcohol are described. Most alcohol is oxidized in the liver, and general principles and overall mechanisms for alcohol oxidation are summarized. The kinetics of alcohol elimination in-vivo and the various genetic and environmental factors that can modify the rate of alcohol metabolism are discussed.
Available from: Xiaodong Wang
- "On the other hand, 18 proteins were shown to be significantly decreased with the fold<0.5 (Table 4). Among the down-regulated proteins, 2 of the most significantly decreased proteins are CYP2E1 and aldehyde dehydrogenase, both of which were known to be critical players in ethanol metabolism . Notably, among the significantly decreased are 4 proteins encoded by Ogdh, Hadha, Acadm, Hmgcs2, which participating in metabolism of long-chain or medium-chain fatty acids, krebs cycle or ketogenesis. "
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ABSTRACT: CYP2E1, one of the cytochrome P450 mixed-function oxidases located predominantly in liver, plays a key role in metabolism of xenobiotics including ethanol and procarcinogens. Recently, down-expression of CYP2E1 was found in hepatocellular carcinoma (HCC) with the majority to be chronic hepatitis B virus (HBV) carriers. In this study, we tested a hypothesis that HBx may inhibit CYP2E1 gene expression via hepatocyte nuclear factor 4α (HNF4α). By enforced HBx gene expression in cultured HepG2 cells, we determined the effect of HBx on CYP2E1 mRNA and protein expression. With a bioinformatics analysis, we found a consensus HNF-4α binding sequence located on -318 to -294 bp upstream of human CYP2E1 promoter. Using reporter gene assay and site-directed mutagenesis, we have shown that mutation of this site dramatically decreased CYP2E1 promoter activity. By silencing endogenous HNF-4α, we have further validated knockdown of HNF-4α significantly decreased CYP2E1expression. Ectopic overexpression of HBx in HepG2 cells inhibits HNF-4α expression, and HNF-4α levels were inversely correlated with viral proteins both in HBV-infected HepG2215 cells and as well as HBV positive HCC liver tissues. Moreover, the HBx-induced CYP2E1 reduction could be rescued by ectopic supplement of HNF4α protein expression. Furthermore, human hepatoma cells C34, which do not express CYP2E1, shows enhanced cell growth rate compared to E47, which constitutively expresses CYP2E1. In addition, the significantly altered liver proteins in CYP2E1 knockout mice were detected with proteomics analysis. Together, HBx inhibits human CYP2E1 gene expression via downregulating HNF4α which contributes to promotion of human hepatoma cell growth. The elucidation of a HBx-HNF4α-CYP2E1 pathway provides novel insight into the molecular mechanism underlining chronic HBV infection associated hepatocarcinogenesis.
Available from: Kusum K Kharbanda
- "However , it has been unequivocally recognized that most of the detrimental effects of excessive alcohol consumption are due to its metabolism (Cederbaum, 2012; Zakhari, 2006). Alcohol dehydrogenase (ADH), predominantly a liver enzyme, metabolizes alcohol to generate acetaldehyde, a prime suspect in many deleterious effects of alcohol (Cederbaum, 2012; Zakhari, 2006). While simultaneously generating acetaldehyde , ADH converts the coenzyme, nicotinamide adenine dinucleotide (NAD + ) to its reduced form, NADH (Crow, 1985). "
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ABSTRACT: Li and colleagues (2014) in this issue report that dietary nicotinic acid (NA) supplementation ameliorates ethanol-induced hepatic steatosis, but a deficiency does not worsen injury induced by alcohol alone. The authors further present some mechanistic insights into the protective role of NA supplementation. Results of this and other previous studies in the context of alcoholic liver injury raise one important question as to what should be an adequate dose of NA that will provide the maximum benefit to hepatic and extrahepatic tissues and with minimum adverse effects.
Available from: Beili Wang
- "These differences may be due to the measurement systems (high-performance liquid chromatography [HPLC], vs. capillary electrophoresis) and target subjects (Western vs. Asian populations). Many factors influence CDT values, including atypical phenotype distributions of alcohol dehydrogenase
, amount of daily alcohol consumption, amount of alcohol consumed per drinking session, duration of abstinence before blood sampling, body weight
 and consumption of fermented food. All these factors may contribute to the CDT differences between Han Chinese and other populations. "
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ABSTRACT: Carbohydrate-deficient transferrin (CDT) is a widely used alcohol biomarker. Because of the high prevalence of chronic alcohol abuse in many countries, CDT plays an important role in the areas of traffic, clinical, and forensic medicine. However, CDT levels have not been determined in the Han Chinese population. Therefore, we investigated the frequency of genetic transferrin variants and the relationship between CDT levels and alcohol consumption in this population. From this data, we established a CDT cut-off for Han Chinese and evaluated the analytical performance of the CDT capillary zone electrophoresis system.
The prevalence of transferrin variants was 4.14%. The mean CDT level of the reference group was 0.73%. We recommended CDT level >1.5% as cut off standard of alcohol intake to ensuring the specificity was best. The CDT test total precision for 0.5%, 0.7%, and 1.55% was 14.4%, 11.5%, and 7.2%, respectively. The data showed good linearity in the studied range of 0.6% to 8.2%.
These results demonstrate that CDT is a useful marker to detect heavy daily alcohol consumption. We proposed and evaluated the first CDT cut-off for the Han Chinese population, and we showed that the CDT capillary zone electrophoresis system is a reliable analytic method.
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