FATTY ACID ETHYL ESTERS: BIOLOGICAL MARKERS OF ALCOHOL

与零级代谢物乙醛、脂肪酸乙酯不同， 酯（FAEE）是一级直接，非氧化代谢产物， 乙醇在我们的实验室在1981年描述的是由 酶FAEE合酶。 我们广泛的方法论 开发用于提取和定量这些脂质， 生物样本导致观察到FAEE是 在体内脂肪组织和骨髓中形成，并具有半- 寿命约为24小时，比乙醇长得多。 在初步实验中，浓度高达5400 nmol/g 发生在兔脂肪组织和骨髓中，限度为 2 nmol/g的可检测性;同样，尸检研究显示， 脂肪组织中这些酒精代谢物的存在 酒鬼 在一项初步临床研究中， FAEE允许正确诊断酒精消费， 在摄入五分之四的酒精后长达六天 消费者和八个控制中的八个。 没有误报 因此被发现。 重要的是，FAEE合酶活性具有 在人外周血白细胞中定量。 提出 因此，研究将描述以下比率的有用性： 脂肪组织和骨髓FAEE浓度与白细胞 作为酒精生物学标记的FAEE合酶活性 不依赖于合成酶多态性的消耗 活动 首先，脂肪的时间过程和浓度 将对喂食以下饲料的家兔的组织和骨髓FAEE进行定量 不同量的乙醇长达三个月， 标准化为白细胞FAEE合酶活性。 脂肪组织 FAEE合酶将被表征。 人类研究将包括 脂肪组织FAEE定量在800例患者接受 常规普通外科手术和与获得的结果相关的结果 通过标准问卷评估频率、持续时间和 近期饮酒量。 的药代动力学分析 通过细针抽吸获得的皮下脂肪组织， 将在40例患者中进行骨髓FAEE 在临床研究中心给予乙醇， FAEE浓度相对于外周血白细胞的正常化 FAEE合酶活性。 这些数据将建立 组织FAEE/白细胞合成酶指数的定量有用性 作为酒精消耗的标志，用于诊断医疗 评估、法医案件、高风险工作人员和监督 拒绝饮酒的问题饮酒者身上

Unlike the zero order metabolite, acetaldehyde, fatty acid ethyl esters (FAEE) are first order direct, nonoxidative metabolites of ethanol described in our laboratory in 1981 to be formed by the enzyme FAEE synthase. Our extensive methodological development for extraction and quantitation of these lipids from biological samples has led to the observation that FAEE are formed in vivo in adipose tissue and bone marrow and have a half- life of approximately 24 hours, much longer than that of ethanol. In preliminary experiments, concentrations as high as 5400 nmol/g occur in rabbit adipose tissue and bone marrow with a limit of detectability of 2 nmol/g; similarly, autopsy studies disclose the presence of these alcohol metabolites in adipose tissues of drinkers. In a pilot clinical study, quantitation of bone marrow FAEE allowed the correct diagnosis of alcohol consumption to be made as long as six days after ingestion in four out of five alcohol consumers, and in eight out of eight controls. No false positives were thus detected. Importantly, FAEE synthase activity has been quantitated in peripheral human leukocytes. Proposed studies therefore will characterize the usefulness of the ratio of adipose tissue and bone marrow FAEE concentration to leukocyte FAEE synthase activity as biological markers of alcohol consumption that is independent of polymorphisms in synthase activity. First, the time course and concentration of adipose tissue and bone marrow FAEE will be quantitated in rabbits fed various amounts of ethanol for up to three months and values normalized to leukocyte FAEE synthase activity. Adipose tissue FAEE synthase will be characterized. Human studies will consist of adipose tissue FAEE quantitation in 800 patients undergoing routine general surgery and results correlated to those obtained by a standard questionnaire to assess frequency, duration and quantity of recent alcohol use. Pharmacokinetic analyses of buttock adipose tissue obtained by skinny needle aspiration and bone marrow FAEE will be performed in forty patients administered ethanol in the Clinical Research Center with normalization of FAEE concentrations to peripheral leukocyte FAEE synthase activity. These data will establish the quantitative usefulness of a tissue FAEE/leukocyte synthase index as a marker of alcohol consumption for use in diagnostic medical evaluations, forensic cases, high risk job holders, and surveillance in problem drinkers who deny alcohol ingestion.