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Alcohol and Its Biomarkers: Clinical Aspects and Laboratory Determination is a concise guide to all currently known alcohol biomarkers, their clinical application, and the laboratory methods used to detect them. Pathologists can use this resource to understand the limitations and cost factors associated with each method for determining certain alcohol biomarkers. In addition, interferences in these determinations are discussed, so that clinicians can understand the causes of falsely elevated biomarkers and pathologists and laboratory scientists can potentially eliminate them. The book focuses on the analytical methods used to detect alcohol in blood and urine, the limitations of alcohol determination using enzymatic methods, and the differences between clinical and forensic alcohol measurement. Chapters also cover cutting-edge alcohol biomarkers for potential use.
Amitava Dasgupta received his Ph.D degree in Chemistry from the Stanford University and his fellowship training in Clinical Chemistry from the Laboratory Medicine Department of the University of Washington School of Medicine at Seattle. He is a tenured Full Professor of Pathology and Laboratory Medicine at the University of Texas Health Sciences Center located at the Texas Medical Center at Houston. Dr. Dasgupta has published 196 scientific papers, wrote many invited review articles, and edited, co-edited or wrote 15 books. He is on the Editorial Board of five major medical journals including American Journal of Clinical Pathology, Archives of Pathology and Laboratory Medicine, Therapeutic Drug Monitoring, Clinica Chimica Acta and Journal of Clinical Laboratory Analysis.
Alcohol and Its Biomarkers: Clinical Aspects and Laboratory Determination is a concise guide to all currently known alcohol biomarkers, their clinical application, and the laboratory methods used to detect them. Pathologists can use this resource to understand the limitations and cost factors associated with each method for determining certain alcohol biomarkers. In addition, interferences in these determinations are discussed, so that clinicians can understand the causes of falsely elevated biomarkers and pathologists and laboratory scientists can potentially eliminate them. The book focuses on the analytical methods used to detect alcohol in blood and urine, the limitations of alcohol determination using enzymatic methods, and the differences between clinical and forensic alcohol measurement. Chapters also cover cutting-edge alcohol biomarkers for potential use.
Auteur
Amitava Dasgupta received his PhD degree in Chemistry from Stanford University and his fellowship training in Clinical Chemistry from the Laboratory Medicine Department of the University of Washington School of Medicine at Seattle. He is a tenured Full Professor of Pathology and Laboratory Medicine at the University of Texas Health Sciences Center located at the Texas Medical Center at Houston. Dr. Dasgupta has published 210 scientific papers, written many invited review articles, and has edited, co-edited or written 15 books. He is on the Editorial Board of five major medical journals including American Journal of Clinical Pathology, Archives of Pathology and Laboratory Medicine, Therapeutic Drug Monitoring, Clinica Chimica Acta and Journal of Clinical Laboratory Analysis.
Échantillon de lecture
Chapter 2 Genetic Aspects of Alcohol Metabolism and Drinking Behavior
This chapter discusses the various pathways of alcohol metabolism, including alternative pathways in alcoholics that may cause the generation of free radicals and oxidative stress. Gender differences in alcohol metabolism and the effect of food on alcohol absorption are also addressed. Keywords
Alcohol metabolism; alcohol dehydrogenase; aldehyde dehydrogenase; polymorphism
Contents
2.1 Introduction 37
2.2 Alcohol Absorption: Effect of Food 37
2.3 First-Pass Metabolism of Alcohol 39
2.4 Alcohol Metabolism 40
2.4.1 Non-Oxidative Pathways of Alcohol Metabolism 42
2.4.2 Factors Affecting Alcohol Metabolism 43
2.5 Genes Encoding Alcohol Dehydrogenase 45
2.5.1 Polymorphism of Alcohol Dehydrogenase Genes 46
2.6 Genes Encoding Aldehyde Dehydrogenase 48
2.6.1 Polymorphisms of Alcohol Dehydrogenase and Aldehyde Dehydrogenase Genes that Protect Against the Development of Alcohol Use Disorder 51
2.6.2 Polymorphism of Alcohol Dehydrogenase and Aldehyde Dehydrogenase Genes that may Increase the Risk of Developing Alcohol Use Disorder 56
2.7 Polymorphism of the CYP2E1 Gene 59
2.8 Conclusions 59
References 60 2.1 Introduction
Ethanol, commonly referred to as "alcohol," is a small water-soluble polar molecule with a molecular weight of 46. The ethanol molecule contains a hydroxyl (-OH) functional group. Alcohol (ethanol) is a nutrient with a caloric value of approximately 7 kcal/g, whereas protein has a caloric value of 4 kcal/g and fat produces 9 kcal/g. After ingestion, alcohol is readily absorbed, but a small amount also undergoes first-pass metabolism. Absorption of alcohol from the gastrointestinal tract depends on how fast the person is drinking as well as whether or not alcohol is consumed with food. After absorption, alcohol is distributed in various tissues and also undergoes extensive metabolism and finally elimination. Although the majority of alcohol is metabolized via the oxidative pathway mainly involving two enzymes-alcohol dehydrogenase and aldehyde dehydrogenase-a small amount is also oxidized by the liver cytochrome P450 enzyme system, most commonly CYP2E1, especially in the presence of a high blood alcohol level. Other enzymes, such as catalase, may also be capable of metabolizing alcohol, but they represent a minor pathway. Polymorphisms of genes coding both alcohol dehydrogenase and aldehyde dehydrogenase enzymes affect blood alcohol level, and some polymorphisms may protect an individual from alcohol abuse. Minor non-oxidative metabolic pathways for alcohol involve conjugation with glucuronic acid yielding ethyl glucuronide and conjugation with sulfate to produce ethyl sulfate. 2.2 Alcohol Absorption: Effect of Food
Alcohol is absorbed from both the stomach and small intestine. A small amount of alcohol that is not absorbed is found in the breath and is the basis of breath analysis of drivers suspected of driving while intoxicated. In general, it is assumed that approximately 1-5% of alcohol is excreted by the lungs, and 1-3% is excreted via other routes such as urine (0.5-2.0%) and sweat (up to 0.5%). A very small amount of alcohol is also metabolized by non-oxidative pathways, and products of such reactions are often used as alcohol biomarkers, such as ethyl glucuronide and ethyl sulfate. The overall elimination process of alcohol can be described by a capacity-limited model similar to the Michaelis-Menten model of enzyme kinetics [1]. When alcohol is consumed, approximate
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