Hver enzymes

Toxicological studies have demonstrated that there are no important problems with fluconazole. Therapeutic doses of fluconazole may cause enzyme induction in the Hver. This suggests that interactions with other dmgs cannot be excluded. The side effects are similar to those of itraconazole and include nausea, headache, and vertigo. Occasionally, increased Hver enzymes may be noted. Like itraconazole, fluconazole is contraindicated during pregnancy. 

Catalase is a hver enzyme that uses hydrogen peroxide to oxidize other substances. In vivo, the catalase system does not play a significant role in ethanol metabolism, probably because the quantities of hydrogen peroxide available are insufficient for ethanol metabolism. 

L A. Nephrotoxicity is the most common and most serious toxicity associated with amphotericin B administration. This is manifested by azotemia (elevated serum blood urea nitrogen and creatinine), and by renal tubular acidosis, which results in the wasting of potassium and magnesium in the urine (leading to hypokalemia and hypomagnesemia, requiring oral or intravenous replacement therapy). Normochromic normocytic anemia is also seen with long-term amphotericin B administration. Elevation of hver enzymes is not associated with the use of amphotericin B. 

Four weeks after receiving a bone marrow transplant, Mary Smith developed jaundice and a skin rash on her hands, feet, and face. She also had occasional episodes of vomiting and diarrhea. Qtnical chemistry results showed her serum hver enzymes (LDH, ALT) and bUirubin level to be elevated. What is the most likely cause of Mary s symptoms and what is the best therapy ... 

A 62-year-old woman with normal hver function tests took troghtazone 400 mg/day in combination with gli-clazide 80 mg/day and pravastatin (125). After 9 months her transaminases were slightly above normal, but the HbAic was 7.0% and treatment was continued. Her hver enzymes were measured monthly and after 19 months rose abruptly. Troghtazone was withdrawn immediately and she received insulin. Her hver enzymes improved rapidly. A biopsy showed hepatic necrosis round the central vein and a mild inflammatory infiltrate and fibrosis in the portal area compatible with protracted acute hepatitis. A lymphocyte stimulation test and a skin test were negative for troghtazone. 

Glycerol kinase (which converts glycerol to glycerol 3-phosphate) is a hver enzyme in this way glycerol enters the gluconeogenesis pathway. 

All statins share an HMG-like moiety which is linked to rigid hydrophobic groups (Figure 12.3). Lovastatin and simvastatin are lactone prodrugs which are converted to the active open hydroxyl acid form in the hver. Enzyme studies show that the statins are competitive inhibitors of HMGR with respect to HMG-CoA and have K values in the 0.1-2.3 nM range [62]. Crystal structure studies have revealed that the statins occupy the active site where HMG-CoA binds but do not affect NADPH binding [63]. 

Table 1 Percentage distribution of 0 in glucose 6-phosphate formed during the time course of reactions of [l- C]-ribose 5-phosphate with rat hver enzyme preparation (42)...

Martin, K., Schlotter, B., MuBer-Hocker, J., Loeschke, K., Pongratz, D., Folwaczny, C. 26-year old female patient with elevated hver enzymes. Z. Gastroenterol. 2002 40 885-890... 

A 45-year-old man took acarbose 50 mg tds for a year and developed an aspartate transaminase of 62 U/1 and an alanine transaminase of 127 /I, with negative serology 3 months later the alanine transaminase was 153 U/1. After withdrawal of acarbose his hver enzymes normalized (46). 

A 73-year-old woman who had taken acarbose 450 mg/ day for 3 months became very tired and icteric (50). Her total bilirubin was 427 pmol/l (direct bihrubin 335 pmol/l) and her hver enzymes were very high. Liver biopsy showed cholestasis and cytolysis without eosinophils. Acarbose was continued for 3 days and her condition did not change. When the acarbose was withdrawn she improved rapidly. 

A 75-year-old man taking insuhn about 40 U/day was given metformin 500 mg bd (72). He also used enteric-coated aspirin, diltiazem XR, ibuprofen, and lovastatin. Two months later his hver enzymes were raised, but he... 

A 27-year-old woman at 31 weeks of a second pregnancy was admitted in premature labor and treated with intravenous fenoterol 7.5 mg/day. Within 48 hours her hver enzymes were raised. Because the hver function tests became progressively worse and she had epigastric pain and severe nausea, the fenoterol was withdrawn after 9 days. The liver function tests quickly normalized and there appeared to be a clear relation between the administration of fenoterol and the occurrence of hver damage. 

A middle-aged woman who had taken germanium lactate-citrate for at least a year (with an estimated cumulative dose of 32.1 g of germanium) developed renal insufficiency with a creatinine clearance of 10 ml/minute, raised creatine kinase activity, and moderately raised hver enzymes. Biopsy showed highly vacuolated cytoplasm in the epithelial cells of the distal renal tubules and microvesicular and macrovesicular steatosis of centrilobular hepatocytes. After withdrawal of the germanium the laboratory values normalized but moderately severe renal impairment persisted (SEDA-16, 231). 

A 62-year-old woman with rheumatoid arthritis developed swelling and pain of both knees. Aurothiomalate was given in a test dose of 12.5 mg, followed the next day by a dose of 25 mg, and then 50 mg twice weekly (total cumulative dose 137.5 mg). She had a leukocjde count of 2.2 X 10 /1, a normochromic anemia, and a normal platelet count. Her hver enzyme activities were raised. Aurothiomalate was withdrawn and about 6 weeks later her liver function tests returned to normal and her white cell count rose to 6.9 x 10 /1. 

Lambert M, Laterre PF, Leroy C, Lavenne E, Coche E, Moriau M. Modifications of hver enzymes during heparin therapy. Acta Clin Belg 1986 41(5) 307-10. 

In patients taking glucocorticoids for Addison s disease, rifampicin may necessitate an increase in glucocorticoid dosage. Thus, incipient adrenal insufficiency can be unmasked by rifampicin (SEDA-13, 261). The phenomenon is due to hver enzyme induction (29). 

Because of the rare and unpredictable nature of hepatobihary reactions to terbinafine, the mechanism of hepatotoxicity has been hypothesized to be either immunological or metabolically mediated. A potentially toxic reactive metabolite of terbinafine, 7,7-dimethylhept-2-ene-4-jmal (TBF-A), the A-dealkylation product of terbinafine, has been identified in vitro (43). The authors speculated that this allylic aldehyde metabolite, formed by hver enzymes and conjugated with glutathione, would be transported across the canalicular membrane of hepatocytes and concentrated in the bile. The reactive monoglutathione conjugate could bind to hepatobiliary proteins and cause direct toxicity. Alternatively, it could modify canahcular proteins and lead to an immune-mediated reaction, causing cholestatic dysfunction. 

Committee (SADRAC) in the period 1965-95. There were 23 hver reactions with a snspected cansal relation to oral low-dose tetracychne derivatives. A cansal relation was considered likely in three cases and possible in eight, giving an incidence of ronghly one in 18 million defined daily doses. There were no deaths from these liver reactions, and hver enzyme activities normalized in all cases without any serious chnical consequences. The authors remarked that the frequency of hver reactions resulting from tetracyclines may be somewhat higher, as previous studies in Sweden suggest that only 20-50% of severe adverse reactions are reported to SADRAC (106). 

There have been several reports of hepatotoxicity attributed to herbal medicines containing L. tridentata leaves (1,2). Of 18 reports of illnesses associated with the ingestion of chaparral, there was evidence of hepatotoxicity in 13 cases (3). The presentation was characterized by jaundice with a marked increase in serum hver enzymes at 3-52 weeks after ingestion, and it resolved 1-17 weeks after withdrawal. The predominant pattern of liver damage was cholestatic in four cases there was progression to cirrhosis and in two there was acute fulminant liver failure that required liver transplantation. 

Coluccio, D., R. Nicklaus, S. Schneider, M. Lewis, and L. Hall. 2000. Evaluation of the Biotrin alpha-glutathione S-transferase (a-GST) enzyme immunoassay (ElA) in detecting liver changes compared to standard hver enzymes. Clinical Chemistry 46 A140. 

One monoamine oxidase has been found soluble in nature, and has been purified. This is the enzyme of blood serum, which has been purified 200-fold from steer plasma. The specificity of the serum enzyme is more restricted than those of the hver enzymes tryptamine and epinephrine are not oxidized rapidly, if at all, although phenylethylamine is a substrate. The polyamines spermine and spermidine are among the best substrates, and decamethylenediamine, but not shorter diamines, is also attacked. Aromatic substitutions on methylamine form substrates that permit spectrophotometric assays. Benzylamine and furfurylamine, for example, which do not absorb fight in the region used, are converted to benzaldehyde and furfuraldehyde, respectively these products have absorption maxima near 250 mja and 275 m/ . 

Problem 8.22 Reduction of pyruvic acid by NADH using the hver enzyme lactate dehydrogenase yields exclusively (5)-lactic acid. Write the Fischer projection of this product. Why does only a single product form ... 

---