Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.2.1.7 (BAL)
 1,977 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Evidence obtained by biochemical analysis of BAL fluids from patients with ARDS indicates that at least 2 important pathogenic events take place in the pulmonary tissues. These are the release of neutrophil elastase and the generation of oxidants. Both events can lead to severe pulmonary injury as has been demonstrated in experimental animals. To better understand the mechanisms of oxidant damaged cells, H2O2 was added to cultured cells. H2O2 compromises a multitude of cellular functions, the combination of which leads to cell death. DNA is an important target for oxidant-induced injury. The formation of DNA strand breaks leads to activation of pADP-RP which in turn causes depletion of NAD and ATP, followed by Ca++ influx and eventually cell lysis. Inhibition of pADP-RP prevented cell lysis, but not DNA damage. A similar sequence of events has been described for cell injury following DNA damage induced by gamma-irradiation and alkylating agents and was proposed to be a suicide mechanism for cells with irreversibly damaged DNA. Sublethal doses of H2O2 will delay cell replication, but not necessarily prevent it.
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PMID:Biochemical events associated with pulmonary failure in shock and trauma. 244 44

The blood alcohol level cycle (BALC) of the intragastric tube feeding model first described by Tsukamoto et al., has three separate essential mechanistic components. The first is the requirement for an intact functioning thyroid. The evidence for this is that propylthiouracil or severance of the pituitary stalk completely prevents the cycle. What happens instead of the cycle is that the blood alcohol level rises to a lethal level when ethanol is given continuously at a dose of 11 g/kg/day by stomach tube. When excess thyroid hormone is given orally it markedly attenuates the cycle because it interferes with the changes in the level of thyroid hormone during the cycle. The second component is norepinephrine. Catecholamines are markedly elevated at the peaks of the cycle. Both propranolol and phenoxybenzamine, which are beta- and alpha-blockers, prevent the cycle. Also, when catecholamines are fed in excess in the form of ephedrine, the cycle is eliminated. The third element essential to the cycle is the generation of NAD to support the oxidation of alcohol by alcohol dehydrogenase. When complex I (NADH dehydrogenase) of the mitochondrial electron transport chain is inhibited by feeding rotenone, the cycle is totally eliminated and blood alcohol levels remain constant at 200 mg/%. Thus NADH increases and NAD decreases at the peak of the cycle. Without the fluxuation of NAD, ADH activity cannot fluctuate during the cycle and the cycle is prevented. The significance of the BALC in the understanding of alcohol liver disease pathogenesis is that there's a marked difference in the gene expression and liver toxicity when the peaks and troughs of the cycle are compared. The expression of 1000+ genes is either two-fold up or down regulated as determined by microarray analysis. At the peaks there is increased liver pathology, especially inflammatory changes in the liver associated with an increase of iNOS expression. The genes responsive to hypoxia inducible factor 1alpha (HIF1alpha) regulation are increased including the expression of erythropoietin, adrenomedullin and adrenergic receptor alpha 1a and d. The expression of prolyl hydroxylase, which destabilizes HIF1alpha, increases when the BAL drops to low levels during the cycle. The level of oxygen, as measured on the surface of the liver, is decreased at the peaks, compared to control livers. The NADH/NAD ratio is markedly increased and ATP levels are markedly decreased at the BAL peaks. Also, endotoxin in the blood is very high at the peaks and very low at the troughs. When the blood alcohol levels fall during the cycle, there is an increase in ALT, suggesting that reoxygenation from the hypoxic state at the peaks causes an ischemic reperfusion injury-like lesion in the liver. At this time there is also an increase in expression of many important enzymes such as manganese SOD. Genes such as c-fos and CTGF are increased in expression. These contrasting findings at the peaks and troughs indicate that the blood alcohol levels, which fluctuate up and down, change the gene expression and the pathology of the liver.
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PMID:The pathogenesis and significance of the urinary alcohol cycle in rats fed ethanol intragastrically. 1634 1

Betaine aldehyde dehydrogenase (BADH) catalyses the irreversible oxidation of betaine aldehyde to glycine betaine with the concomitant reduction of NAD(P)(+) to NAD(P)H. In the opportunistic pathogen Pseudomonas aeruginosa, this enzyme (PaBADH) could be an antimicrobial target. Several aldehyde dehydrogenases (ALDHs) are inactivated by arsenite in the presence of a low molecular thiol, a finding that was interpreted as a demonstration of the existence of vicinal thiols in these enzymes. As part of our studies on the susceptibility to chemical modification of the catalytic cysteine (C286) of PaBADH, we treated the enzyme with two arsenical reagents widely used to inhibit enzymes that have vicinal thiols: sodium m-arsenite plus 2,3-dimercaptopropanol (arsenite-BAL) and phenylarsine oxide (PAO). Here we report that they readily and reversibly inactivate PaBADH, even though the four cysteine residues of this enzyme (C286, C353, C377, and C439) are far from each other in the three-dimensional structure. Modification of PaBADH by both reagents was reversible by an excess of a dithiol (dithiothreitol), but only the PAO-modified enzyme could be reactivated by a monothiol (2-mercaptoethanol). C286 is the reactive residue as indicated by the following findings: (i) betaine aldehyde and NADP(+) afforded full protection against enzyme inactivation; (ii) the mutant proteins C353A, C377A, and C439A showed similar inactivation kinetics that the wild-type enzyme, and (iii) pretreatment of PaBADH with arsenite-BAL prevented irreversible inactivation by N-ethylmaleimide. Our results confirm previous findings on other ALDHs, and indicate that these vicinal thiol-specific reagents readily react with certain monothiols, such as the one of the catalytic cysteinyl residue of ALDHs. As arsenicals are being recently used to treat certain cancers, human ALDHs, even those not having conformationally vicinal thiols, may be unsuspected targets in these treatments.
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PMID:Reaction of the catalytic cysteine of betaine aldehyde dehydrogenase from Pseudomonas aeruginosa with arsenite-BAL and phenylarsine oxide. 1902 74