Disease relevance of Isopentanol

• Pretreatment of cultured rat hepatocytes with ethanol alone or in combination with isopentanol, the major higher chain alcohol in alcoholic beverages, significantly increased CYP3A and acetaminophen (APAP) bioactivation, with no increase in APAP toxicity [1].
• The gene coding for alcohol acetyltransferase ( ATF2), which catalyzes the esterification of isoamyl alcohol and acetyl coenzyme A (acetyl-CoA), was cloned from Saccharomyces cerevisiae and expressed in Escherichia coli [2].

Psychiatry related information on Isopentanol

• Plasma ethanol concentration, reaction time, and electroencephalogram (EEG) were recorded in 6 normal men after ingestion of ethanol along (Group 1), whiskey (Group 2), or a mixture of ethanol, n-propanol, n-butanol, and iso-amyl alcohol (Group 3) [3].

High impact information on Isopentanol

• We found that several alcohols, notably isoamyl alcohol and 1-butanol, stimulate filamentous growth in haploid cells in which this differentiation is normally repressed [4].
• This pathway is not required for the synthesis of isoamyl alcohol because abolition of branched-chain alpha-keto acid dehydrogenase activity in an lpd1 disruption mutant did not prevent the formation of isoamyl alcohol [5].
• A third route utilizes alpha-ketoisocaproate reductase (a novel activity in Saccharomyces cerevisiae) but with no role in the formation of isoamyl alcohol from alpha-hydroxyisocaproate because cell homogenates could not convert alpha-hydroxyisocaproate to isoamyl alcohol [5].
• Isoamyl alcohol (IAA) induces a phenotype that resembles pseudohyphae in the budding yeast Saccharomyces cerevisiae [6].
• In yeast, the pseudohyphal phenotype induced by isoamyl alcohol results from the operation of the morphogenesis checkpoint [6].

Chemical compound and disease context of Isopentanol

• Subchronic toxicity studies of 3-methyl-1-butanol and 2-methyl-1-propanol in rats [7].
• Isoamyl acetate production from the substrate isoamyl alcohol in E. coli and C. acetobutylicum cultures was determined by head-space gas analysis [8].

Biological context of Isopentanol

• The concept is tested experimentally on a laboratory-scale using, as a model, the esterification of isoamyl alcohol and propionic acid in hexane catalyzed by an immobilized lipase [9].
• The analysis is made on a porous polymer packing material, by determining the 3-methyl-1-butanol formed on alkaline hydrolysis of the drug [10].
• The model was validated by using overall uptake data from rodent inhalation studies for three "unreactive" vapors that were either completely inert (i.e., acetone), reversibly ionized in aqueous media (i.e., acrylic acid), or prevented from being metabolized by an enzyme inhibitor (i.e., isoamyl alcohol) [11].
• At a concentration of 0.5% (v/v), isoamyl alcohol induced the formation of hyphal-like extensions in haploid and diploid strains of Saccharomyces cerevisiae in liquid complex medium [12].
• To identify genes encoding enzymes with major influence on product formation, a genome-wide gene expression analysis was carried out with S. cerevisiae cells grown at pH 3.0 (optimal for 3-methyl-1-butanol formation) and pH 5.0 (yeast cultivated under standard conditions) [13].

Anatomical context of Isopentanol

• Exposure of cultured chick embryo hepatocytes to ethanol, isobutanol, or isopentanol, the predominant alcohols present in commercial alcoholic beverages, resulted in increased metabolism of aminopyrine or biphenyl by the intact cells [14].
• The method involves a single-step extraction from alkalized plasma, cerebrospinal fluid, or urine into n-hexane/isoamyl-alcohol (99/1, v/v) [15].
• Synergistic induction of cytochrome P450 by ethanol and isopentanol in cultures of chick embryo and rat hepatocytes [16].
• An extraction procedure using mixtures of phenol, chloroform, and isoamyl alcohol originally applied to quench mitochondria for determining adenylates proved suitable also for the quantification of reduced and oxidized pyridine nucleotides yielding recoveries of more than 90% [17].
• To obtain information on cell wall synthesis and its relationship to morphology, we examined the induction of cell extensions of yeast upon the addition of isoamyl alcohol in osmotically fragile mutants that had mutations in genes related to the cell integrity pathway through activation of the mitogen-activated protein kinase cascade [18].

Associations of Isopentanol with other chemical compounds

• The drugs are extracted at pH 10.5 into hexane/isoamyl alcohol, which is evaporated and the residue chromatographed [19].
• The N-[3H]-methyl]histamine generated was selectively extracted into toluene/isoamyl alcohol (3:2) and the quantity of the tritium in the sample was determined by liquid- scintillation counting [20].
• In the present study, short-term (1 wk) pretreatment with ethanol plus isopentanol, the predominant alcohols in alcoholic beverages, caused no histologically observed liver damage in either C3H/HeJ mice or endotoxin-responsive C3H/HeN mice, despite an increase in nitrotyrosine levels in the livers of C3H/HeN mice [21].
• Isoamyl acetate is synthesized from isoamyl alcohol and acetyl coenzyme A by alcohol acetyltransferase (AATFase) in Saccharomyces cerevisiae and is hydrolyzed by esterases at the same time [22].
• The knowledge of potential mechanisms has expanded to include effects of other alcohols, such as isopentanol, induction of CYP enzymes other than CYP2E1 and glutathione depletion [23].

Gene context of Isopentanol

• Isopentanol, the major higher chain alcohol in alcoholic beverages, also induced CYP3A and CYP2E1 [24].
• The ATF2 gene encodes alcohol acetyltransferase II, which catalyses the synthesis of isoamyl acetate from acetyl coenzyme A and isoamyl alcohol [25].
• We found that isoamyl alcohol induces cell extensions in pkc1 deletion mutants but not in mutants with mutations in genes positioned downstream or upstream of the PKC1 gene [18].
• These results indicate that pyruvate decarboxylase encoded by the PDC1 gene contributes, at least partially, to the decarboxylation of alpha-KIC for isoamyl alcohol formation [26].
• In another human hepatocyte culture, however, the amount of immunoreactive CYP3A increased by isopentanol was less than that increased by rifampicin [24].

Analytical, diagnostic and therapeutic context of Isopentanol

• Adducts were eluted from the immunoaffinity columns, hydrolyzed with acid, and extracted into isoamyl alcohol, before being subjected to high-performance liquid chromatography [27].
• With isopentanol alone, the amounts of CYP2H1 and ALAS mRNAs at 4 to 6 h were similar to those observed after treatment with the alcohol combination, but declined by 11 h [28].
• Total RNA was extracted using proteinase K digestion and phenol/chloroform/isoamyl alcohol extraction, and HCV RNA was detected by standard RT-PCR using primers from the highly conserved 5' untranslated region [29].
• After isolation by centrifugation, the cpDNA is purified by the combined action of proteolytic enzymes and detergents, followed by the elimination of proteins using a mixture of chloroform and isoamyl alcohol [30].
• The homogeneity of these two polysaccharides was established by repeated precipitation with iso-amyl alcohol, gel-filtration chromatography and sedimentation analysis [31].

References