L-Alanine transaminase

A 54-year-old woman had fatigue and dark urine after taking acarbose 50 mg tds for 5 months (57). Her aspartate transaminase was 2436 U/l, alanine transaminase 2556 U/l, y-glutamyl transpeptidase 601 U/l, and alkaline phosphatase 174 U/l serology was negative and she had a normal liver and gall bladder on ultrasound. Her liver enzymes normalized 5 months after withdrawal. 

A 58-year-old woman started to feel ill 2 weeks after starting to take rosiglitazone 4 mg/day (72). One week later her peak aspartate transaminase was 5.2 pkat/l, alanine transaminase 4.2 pkat/l, and bilirubin 41 pmol/... 

Kim et al. have recently reported [39] the use of an (O-transaminase from Vibrio fluvialis as shown in Scheme 2.36. In order to shift the equiUbrium towards formation of the product amine they employed the use of excess L-alanine as the amino... 

A 45-year-old man took acarbose 50 mg tds for a year and developed an aspartate transaminase of 62 U/l and an alanine transaminase of 127 H, with negative... 

A 49-year-old woman developed jaundice after taking pioglitazone 30 mg/day for 6 weeks, and after 3 weeks the alanine transaminase was 131 U/l and aspartate transaminase 79 U/l (106). Tests for viral hepatitis were negative. A liver biopsy showed marked portal edema, patchy chronic inflammation, a cellular infiltrate, and marked bile duct proliferation. There was no fibrosis. The laboratory results worsened after pioglitazone was withdrawn, and 1 month after withdrawal the bilirubin reached a peak of 585 pmol/1. Over the next 8 weeks the symptoms and laboratory tests improved, and after 6 months her condition was the same as when she had started to take pioglitazone. 

A 61-year-old man developed hepatotoxicity 8 days after starting to take rosiglitazone 4 mg/day, and it was withdrawn (109). The alanine transaminase was 28 pikat/l, aspartate transaminase 23 gkat/l, alkaline phosphatase 8.7 pkat/l, total bilirubin 14 gmol/l, and direct bilirubin 13 pmol/l. All the tests were normal 5 months later. He had taken troglitazone for 1 week 8 months before this incident but had stopped because of nausea and an upset stomach. 

A 69-year-old man taking rosiglitazone 4 mg/day and metformin 500 mg/day developed hepatic failure within a week and both drugs were withdrawn (110). His alanine transaminase was 32 pkat/l, aspartate transaminase 47 pikat/l, total bilirubin 65 pmol/l, and direct bilirubin 41 pmol/l. He became comatose and the aspartate... 

A 38-year-old woman was given insulin when glibenclamide and acarbose failed. Troglitazone 400 mg/day was added and increased to 800 mg/day 1 month later. After 2 months her liver function tests were normal, but she developed jaundice after 4 months. Total and direct bilirubin were 127 and 101 pmol/l and alanine transaminase was 34 pkat/l. After withdrawal of troglitazone her symptoms disappeared and her liver function tests normalized within several months. Metformin 1000 mg bd reduced her insulin requirement. Rosiglitazone 4 mg bd was added and her liver function tests remained normal for 10 months. 

For two transaminases the remaining unknown stereochemical parameter was determined by demonstrating an internal transfer of tritium (dialkyl amino acid transaminase) [28] or deuterium (pyridoxamine-pyruvate transaminase) [27] from the a-position of the substrate L-alanine to C-4 of the cofactor. Internal hydrogen transfer from the a-position of the substrate amino acid to C-4 of PLP has also been demonstrated for two of the abortive transamination reactions, those catalyzed by tryptophan synthase fi2 protein [32] and by aspartate-/8-decarboxylase [31]. In addition, the same phenomenon must occur in alanine transaminase, as deduced from the observation that the enzyme catalyzes exchange of the /8-hydrogens of... 

L-Lactic acid, in the presence of NAD, is oxidised to pyruvate in a reaction catalysed L-lactate deshydrogenase (l-LDH). The equilibrium of the reaction is forced in the direction of the products by the elimination of pyruvate by reacting it with L-glutamate, resulting in the formation of L-alanine. This reaction is catalysed by glutamate-pyruvate-transaminase (GPT) ... 

Bedogni, G., Miglioli, L., Battistini, N., Masutti, F., Tiribelli, C., Bellentani, S. Body mass index is a good predictor of an elevated alanine transaminase level in the general population hints from the Dionysos study. Dig. Liver Dis. 2003 35 648-652... 

A 66-year-old man had taken trovafloxacin 100 mg/day for 4 weeks for refractory chronic sinusitis (10). For several years he had also taken allopurinol, doxepin, hydrochlorothiazide, losartan, metoprolol, and nabumetone. He developed nausea, vomiting, malaise, and abdominal distension. His white cell count was 8000 x 10 /1 with 16% eosinophils his serum aspartate transaminase was 537 IU/1, alanine transaminase 841 IU/1, direct bilirubin 17 pmol/l total bilirubin 27 pmol/l, alkaline phosphatase 111 IU/1 blood urea nitrogen 5 pmol/l and creatinine 190 pmol/l. Tests for hepatitis A, B, and C were negative. A biopsy of the liver showed centrilobular and focal periportal necrosis and eosinophilic infiltration the sinusoids were dilated and contained lymphocytes and eosinophils many hepatocytes were undergoing mitosis. After withdrawal of trovafloxacin and treatment with prednisone, his hepatic and renal function returned to normal, and the eosinophilia gradually resolved. 

A 63-year-old man, who had taken amiloride and alfuzosin for 9 months for hypertension and benign prostatic hyperplasia, became jaundiced. His aspartate transaminase was 3013IU/1, alanine transaminase 2711 IU/1, alkaline phosphatase 500 IU/1, and total bilirubin 415 pmol/l. Viral causes, autoimmune hepatitis, and biliary obstruction were excluded. After withdrawal of alfuzosin, his liver function tests gradually returned to normal within 6 months. 

The safety and efficacy of ABLC 5 mg/kg/day in patients with neutropenia and intolerance or refractoriness to amphotericin deoxycholate have been reported in two smaller series of 25 treatment courses from the UK. In one, the mean serum creatinine at the start of therapy was 139 pmol/l and at the end of therapy 132 pmol/l there were no infusion-related adverse events (27). There was an increase in alanine transaminase activity in 12 of the 22 analysed treatment courses. In the other, there was an increase in serum creatinine in 5 of 18 courses (28%), and hypokalemia (less than 2.5 mmol/1) in two courses (11%) premedication for infusion-associated reactions was required in three courses (17%) (28). There were modest increases in serum alanine transaminase activities in five patients (30%). 

In 25 children with chronic hepatitis C, pretreatment positivity for liver/kidney microsomal type 1 (LKM-1) antibodies was associated with more frequent treatment-limiting increases in serum alanine transaminase activity (256). Withdrawal of interferon alfa-2b because of hypertransaminasemia was required in three of four LKM-1 positive children compared with two of the 21 LKM-1 negative children. Although none developed features of autoimmune hepatitis, careful surveillance of hepatic function is recommended in LKM-l-positive patients. 

A 3.5-year-old girl was admitted after accidental ingestion of 50-60 tablets of ferrous sulfate 200 mg. She was unresponsive and her serum iron concentration was 138 pmol/l. She required resuscitation and ventilation and an intravenous infusion of deferoxamine was started at a rate of 15 mg/kg/hour, reducing to 5 mg/kg/hour 20 hours later, when the iron concentration was 27 pmol/l. At that time, her liver function deteriorated, with raised alanine transaminase activity (57 IU/1), raised bilirubin (56 pmol/l), and a coagulopathy with an INR of 2.7. She was given an infusion of A-acetylcysteine 12.5 mg/kg/hour and her hepatic function stabilized. After about 40 hours she had acute respiratory deterioration with tachypnea and hypoxemia. A chest X-ray showed widespread bilateral infiltrates. A diagnosis of acute respiratory distress syndrome was made. 

A 41-year-old man developed severe hepatic dysfunction following a 3.5-week course of terbinafine (250 mg/ day) (40). He had marked pruritus, jaundice, malaise, anorexia, and loin pain. His serum bilirubin rose to a peak of 718 pmol/l with alkahne phosphatase 569 U/1, alanine transaminase 90 U/1, aspartate transaminase 63 U/1, and a prolonged prothrombin time of 21 seconds, unresponsive to vitamin K. Liver biopsy showed canalicular cholestasis consistent with a drug reaction. His symptoms resolved 11 months after drug withdrawal, and his hver function tests normalized after 15 months. 

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