Transaminases alcohols

Alcohol dehydrogenase (5) and leucine a-ketoglutarate transaminase (33,34) contribute to the development of aroma during black tea manufacturing. Polyphenol oxidase and peroxidase are essential to the formation of polyphenols unique to fermented teas. 

Older adults are particularly susceptible to a potentially fatal hepatitis when taking isoniazd, especially if they consume alcohol on a regular basis. Two other antitubercular drugs rifampin and pyrazinamide, can cause liver dysfunction in the older adult. Careful observation and monitoring for signs of liver impairment are necessary (eg, increased serum aspartate transaminase, increased serum alanine transferase, increased serum bilirubin, and jaundice). 

Another common liver disease, alcoholic liver damage produced by moderate to heavy alcoholic intake, is also reflected by an elevation of the serum GOT and GPT activities. The serim glutamyl transferase activity is reported to be a sensitive index of alcoholic intake and can serve to monitor persons on alcoholic withdrawal programs (60). The LD-5 isoenzyme arises mainly from liver tissue, but has a short half-life (61), which is about 1/5 and 1/2 of the half life of the transaminases, GPT and GOT respectively. Some authors consider that a normal LD-5 isoenzyme activity in a jaundiced patient is sufficient evidence to exclude primary liver disease and that obstruction is probably responsible for the jaundice (62). In hemolytic jaundice the LDH-1 and 2 isoenzymes are elevated. 

Hepatocellular damage manifests as elevated serum aminotransferases [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)]. The degree of transaminase elevation does not correlate with the remaining functional metabolic capacity of the liver. An AST level two-fold higher than ALT is indicative of alcoholic liver damage. 

Patients should have blood urea nitrogen, serum creatinine, aspartate transaminase or alanine transaminase, and a complete blood count determined at baseline and periodically, depending on the presence of other factors that may increase the likelihood of toxicity (advanced age, alcohol abuse, and possibly pregnancy). Hepatotoxicity should be suspected in patients whose transaminases exceed five times the upper limit of normal or whose total bilirubin exceeds 3 mg/dL. At this point, the offending agent(s) should be discontinued, and alternatives selected. 

Therapy with INH results in a transient elevation in serum transaminases in 12% to 15% of patients and usually occurs within the first 8 to 12 weeks of therapy. Risk factors for hepatotoxicity include patient age, preexisting liver disease, and pregnancy or postpartum state. INH also may result in neurotoxicity, most frequently presenting as peripheral neuropathy or, in overdose, seizures, and coma. Patients with pyridoxine deficiency, such as alcoholics, children, and the malnourished, are at increased risk, as are patients who are slow acetylators of INH and those predisposed to neuropathy, such as those with diabetes. 

Hepatotoxicity- Duloxetine increases the risk of elevation of serum transaminase levels. The combination of transaminase elevations and elevated bilirubin, without evidence of obstruction, is generally recognized as an important predictor of severe liver injury. Because it is possible that duloxetine and alcohol may interact to cause liver injury, duloxetine should ordinarily not be prescribed to patients with substantial alcohol use. 

Dyspepsia is the most common side effect of zileuton. Liver transaminase levels are elevated in a small percentage of patients taking zileuton. Serum Uver transaminase levels should be monitored and treatment halted if significant elevations occur. Zileuton inhibits the metabolism of theophylline. Thus, when these agents are used concomitantly, the dose of theophylline should be reduced by approximately one-half, and plasma concentrations of theophylline should be monitored closely. Caution should also be exercised when using zileuton concomitantly with warfarin, terfenadine, or propranolol, as zileuton inhibits the metabolism of these agents. Zileuton is contraindicated in patients with acute liver disease and should be used with caution in patients who consume substantial quantities of alcohol or have a history of liver disease. 

Hepatotoxicity. Duloxetine is rarely associated with increases in serum transaminase levels, typically in the first 2 months of treatment. In controlled trials in major depressive disorder, elevations of alanine aminotransferase (ALT) to greater than three times the upper limit of normal occurred in 0.9% (8 of 930) of the duloxetine-treated patients and in 0.3% (2 of 652) of the placebo-treated patients. Current product labeling contains a caution regarding the use of duloxetine in patients with significant alcohol use or chronic liver disease. Postmarketing reports have indicated that increases in transaminases have occurred in some patients with chronic liver disease (Cymbalta 2005). 

Vitamin B6 occurs naturally in three related forms pyridoxine (6.26 the alcohol form), pyridoxal (6.27 aldehyde) and pyridoxamine (6.28 amine). All are structurally related to pyridine. The active co-enzyme form of this vitamin is pyridoxal phosphate (PLP 6.29), which is a co-factor for transaminases which catalyse the transfer of amino groups (6.29). PLP is also important for amino acid decarboxylases and functions in the metabolism of glycogen and the synthesis of sphingolipids in the nervous system. In addition, PLP is involved in the formation of niacin from tryptophan (section 6.3.3) and in the initial synthesis of haem. 

Some examples of emerging enzyme classes that are rapidly making an impact in synthetic organic chemistry are shown in Figure 16.4 alcohol dehydrogenase for the reduction of ketones [30], transaminase [31], and haloalkane dehalogenase... 

A 59-year-old man took troglitazone 400 mg/day for 6 months and alcohol about 40 g/day. He developed weakness and muscle pain. He had mild liver damage. His HbAic concentration was 9.0%. All his muscles were tender, his creatine kinase activity was 10 570 IU/ml, and his myoglobin, aldolase, and aspartate transaminase were raised. Troglitazone was withdrawn. He improved biochemically and clinically. 

A transaminase patented by Celgene Corporation (Warren, NJ), called an co-aminotransferase [(co-AT)E.C. 2.6.1.18] does not require an a-amino acid as amino donor instead it requires a primary amine and hence has the ability to produce chiral amines.125 126 A similar co-AT from Vibrio fluvialis has been described for the production of chiral amines along with chiral alcohols when coupled with AdH or chiral amino acids when coupled with an a-amino acid aminotransferase.127130 Another co-AT, ornithine (lysine) aminotransferase (E.C. 2.6.1.68), has been described for the preparation of a chiral pharmaceutical intermediate used in the synthesis of Omapatrilat, a vasopep-tidase inhibitor developed by Bristol-Myers Squibb, as well as the UAA A1 -piperidinc-6-carboxylic acid.131-132... 

Acute hepatitis induced by intranasal cocaine, with transient increases in liver enzymes, has been reported in three HIV-positive patients (202). All had non-active chronic viral hepatitis with normal immunological status one was seropositive for hepatitis B virus and two were positive for hepatitis C virus. A few days after intranasal cocaine use, serum transaminases rose to high values, and two of the patients had fever, stiffness, sweats, and hepatomegaly. Alcohol and hepatotoxic agents were ruled out. Within a few days, the clinical and laboratory signs of hepatitis improved in all three cases. 

Lflly, M., Bauer, F.F., Styger, G., Lambrechts, M.G., Pretorius, l.S. (2006b).The effect of increased branched-chain amino acid transaminase activity in yeast on the production of higher alcohols and on the flavour profiles of wine and distillates. FEMS Yeast Res., 6, 726-743. 

Acute hepatitis, which may be extremely severe, can occur with extraordinarily heavy acute drinking bouts. The serum transaminase rises after alcohol in alcoholics but not in others. The single case-report that after a binge the cerebrospinal fluid tasted of gin remains unconfirmed. 

Vitamin B Three substances are classed under the term pyridoxine or adermine pyridoxol, pyridoxal and pyridoxamine. Pyridoxine was isolated by various study groups in 1938. Its structure was described by Folkers and Kuhn in 1939. Pyridoxal and pyridoxamine were discovered by Snell in 1942. Pyridoxal phosphate and pyridoxamine phosphate are biologically active substances. Intestinal absorption of Bg is dose-dependent and not limited. In alcoholism, a deficiency of vitamin Bg is encountered in 20—30% of cases, whereas the respective percentage is 50—70% in alcoholic cirrhosis. Vitamin Bg is an important coenzyme for transaminases, which transfer amino groups from amino adds to keto acids. In this way, biochemical pathways between the dtiic acid cycle and carbohydrate and amino acid metabolisms are created. (104)... 

Histologically, non-alcoholic steatohepatitis shows moderate to high-grade, mainly macrovesicular fatty degeneration of the liver cells with inflammatory infiltrates and formation of fibrosis. Cirrhosis frequently develops. Despite the morphological similarity to alcohol-induced fatty liver hepatitis, there is no (noteworthy) alcohol consumption involved in NASH. Viral or autoimmune hepatitis are not detectable either. There are no or only moderate subjective complaints. The transaminases are normal or slightly increased. NASH is mostly associated with obesity and/or type II diabetes, thus NASH is regarded as the hepatic manifestation of a metabolic syndrome. 

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