Search

C32H48O5, orthorhombic, P212121 (no. 19), a = 7.1564(10) Å, b = 17.542(3) Å, c = 23.134(4) Å, V = 2904.2(8) Å3, Z = 4, Rgt(F) = 0.0555, wRref(F2) = 0.1343, T = 273(2) K.

C32H48O5, orthorhombic, P212121 (no. 19), a = 7.1564(10) Å, b = 17.542(3) Å, c = 23.134(4) Å, V = 2904.2(8) Å3, Z = 4, Rgt(F) = 0.0555, wRref(F2) = 0.1343, T = 273(2) K. [ABSTRACT FROM AUTHOR]

Approximately 36% of East Asians (Japanese, Chinese, and Koreans) show a characteristic physiological response to drinking alcohol that includes facial flushing (see Figure 1), nausea, and tachycardia [1] . This [...]

Total gene expression analysis (TOGA) was used to identify genes that are differentially expressed in brain regions between the alcohol-naive, inbred alcohol-preferring (iP), and -nonpreferring (iNP) rats. [alpha]-Synuclein, expressed at >2-fold higher levels in the hippocampus of the iP than the iNP rat, was prioritized for further study. In situ hybridization was used to determine specific brain regions and cells expressing [alpha]-synuclein in the iP and iNP rats. Similar to [alpha]-synuclein mRNA levels, protein levels in the hippocampus were higher in iP rats than iNP rats. Higher protein levels were also observed in the caudate putamen of iP rats compared with iNP rats. Sequence analysis identified two single nucleotide polymorphisms in the 3' UTR of the cDNA. The polymorphism was used to map the gene, by using recombination-based methods, to chromosome 4, within a quantitative trait locus for alcohol consumption that was identified in the iP and iNP rats. A nucleotide exchange in the iNP 3' UTR reduced expression of the luciferase reporter gene in SK-N-SH neuroblastoma cells. These results suggest that differential expression of the [alpha]-synuclein gene may contribute to alcohol preference in the iP rats.

Objective: Family history of alcoholism (FHA) is associated with increased drinking history, which can be a confounding factor in studies of the influence of FHA on the acute response to alcohol. The objective of this analysis was to investigate the association between recent drinking history (RDH) and FHA in a sample of family history positive (FHP; n = 55, 28 women) and family history negative (FHN; n = 55, 29 women) subjects, and to explore the influence of RDH on the response to alcohol during a 60 mg% clamp. Method: RDH was measured using daily diary and timeline followback methods. The total number of drinks in the 4-week (TD28) and 1-week (TD07) intervals prior to the study were determined, as well as the number of drinking days in the same intervals. Dependent measures of brain function were obtained at baseline (BO), immediately after the target BrAC was achieved (B1) and 105 minutes later (B2). The alcohol response was quantified as an initial response (ira = B1-B0) and an adaptive response (ada = B2-B1). The association between RDH and the ira and ada measures was tested using multivariate regression. Results: The RDH measures showed a large variance across subjects, with no significant differences between FHP and FHN groups in the study sample. The initial responses for subjective perceptions of 'high' and 'intoxicated,' Alcohol Sensation Scale scores and scores for the grooved pegboard task were significantly negatively associated with TD28. Acute tolerance to perceptions of 'high' and 'intoxication' was significantly negatively associated with TD28. Conclusions: Heavy drinking history is associated with a decreased initial response to alcohol and greater acute tolerance to alcohol, particularly for subjective measures. Although RDH was not associated with FHA in this study, it may be an important determinant of the response to alcohol. (J. Stud. Alcohol 63: 734-744, 2002), STUDIES INVESTIGATING the influence of family history of alcoholism (FHA) on the acute response to alcohol, both initial and adaptive, could be confounded by the drinking history of subjects. Previous [...]

Human brain oscillations represent important features of information processing and are highly heritable. A common feature of beta oscillations (13-28 Hz) is the critical involvement of networks of inhibitory interneurons as pacemakers, gated by [gamma]-aminobutyric acid type A (GABAA) action. Advances in molecular and statistical genetics permit examination of quantitative traits such as the beta frequency of the human electroencephalogram in conjunction with DNA markers. We report a significant linkage and linkage disequilibrium between beta frequency and a set of GABAA receptor genes. Uncovering the genes influencing brain oscillations provides a better understanding of the neural function involved in information processing.

Interaction between functional polymorphisms of the alcohol-metabolism genes is discussed as related to protection against alcoholism. In Taiwan 340 alcoholic and 545 control Han Chinese were genotyped at three loci related to alcohol dehydrogenase and aldehyde dehydrogenase, the major enzymes of alcohol metabolism. Genetic protection against alcoholism exists in East Asians where variant alleles are seen. Results seem to indicate that protection from one allele may be independent of that from another.

Human class I beta3beta3 is an alcohol dehydrogenase dimer that catalyzes the reversible oxidation of ethanol. Stopped-flow kinetics were employed from pH 6 to 9 with recombinant beta369C, where the beta3 subunit has a Cys substitution for Arg-369, to study the rate-limiting steps in coenzyme association and catalysis. Findings indicated an NADH-induced isomerization of the enzyme from an open to closed conformation. The pH dependence of apparent zero-order rate constants are best represented by a model in which a single ionization limits diminishing rates and agreed with Vmax values for acetaldehyde reaction.