L-aspartate transaminase

A 61-year-old man developed hepatotoxicity 8 days after starting to take rosiglitazone 4 mg/day, and it was withdrawn (109).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man taking rosiglitazone 4 mg/day and metformin 500 mg/day developed hepatic failure within a week and both drugs were withdrawn (110).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 possible explanation for the superiority of the amino donor, L-aspartic add, has come from studies carried out on mutants of E. coli, in which only one of the three transaminases that are found in E. coli are present. It is believed that a branched chain transaminase, an aromatic amino add transaminase and an aspartate phenylalanine aspartase can be present in E. coli. The reaction of each of these mutants with different amino donors gave results which indicated that branched chain transminase and aromatic amino add transminase containing mutants were not able to proceed to high levels of conversion of phenylpyruvic add to L-phenylalanine. However, aspartate phenylalanine transaminase containing mutants were able to yield 98% conversion on 100 mmol l 1 phenylpyruvic acid. The explanation for this is probably that both branched chain transaminase and aromatic amino acid transminase are feedback inhibited by L-phenylalanine, whereas aspartate phenylalanine transaminase is not inhibited by L-phenylalanine. In addition, since oxaloacetate, which is produced when aspartic add is used as the amino donor, is readily converted to pyruvic add, no feedback inhibition involving oxaloacetate occurs. The reason for low conversion yield of some E. coli strains might be that these E. cdi strains are defident in the aspartate phenylalanine transaminase. 

EC2.6.1.1 L-aspartate aminotransferase (glutamate oxaloacetate transaminase) (aminotransferase (transaminase))... 

W13. Wolf, P. L., William, D., Coplon, N., and Coulson, A. S., Low aspartate transaminase activity in serum of patients undergoing chronic hemodialysis. Clin. Chem. 18, 567-568 (1972). 

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 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 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. 

Sizer, I. W., and Jenkins, W. T. (1962). Glutamic Aspartic Transaminase from Pig Ventricles Preparation and Assay of Enzymes. Methods Enzymol 5 677. Stryer, L. (1995). Amino Acid Degradation and the Urea Cycle. In Biochemistry, 4th ed. New York Freeman. 

A 44-year-old man with depression was given hydroxyzine hydrochloride 100 mg/day, clonazepam 2 mg/ day, and citalopram 20 mg/day. Two years before he had tolerated fluoxetine for 6 months for an episode of depression, with good effect. After 7 weeks he developed weakness and weight loss. Physical examination was normal but the serum aspartate transaminase (AsT) was raised at 277 IU/L (reference range < 36 IU/1). His bilirubin was normal. Citalopram was withdrawn and the other drugs were continued intermittently 5 days later the serum aspartate transaminase had fallen by a half, and within 2 months it had returned to normal. 

In the presence of NAD, L-malic acid is oxidised to oxaloacetate in a reaction catalysed by L-malate deshydrogenase (l-MDH). The reaction equilibrium is forced in the direction of the products by the elimination of oxaloacetate, via its reaction with 1-glutamate, resulting in the production of L-aspartate. This reaction is catalysed by glutamate-oxaloacetate-transaminase (GOT) ... 

In the widely used colorimetric assay of SGOT and SGPT (R2), serum is incubated at 37 °G with phosphate-buffered L-aspartate/a-oxoglutarate or DL-alanine/a-oxoglutarate, respectively, the reaction terminated after a definite interval by addition of 2,4-dinitrophenylhydrazine in dilute HCl, and after a period at room temperature the hydrazones of oxalace-tate or pyruvate so formed are treated with dilute alkali and the optical density measured against water at 505 mp the results are read from standard curves of optical density against transaminase activity. 

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. 

In a retrospective analysis of a stndy of iV-phosphonoacetyl-L-aspartate (250 mg/m ) followed by weekly bolnses of flnoronracil (600-800 mg/m ) in 44 patients with metastatic colorectal cancer, five of 17 patients with complete or partial responses to therapy developed transient ascites (with or withont associated hypoalbuminemia) compared with one of 27 withont snch a response (101). Other significant findings in some of the responders inclnded raised bihmbin concentrations and transaminase activities from metastasis. The anthors cautioned that the adverse effects observed do not necessarily represent disease progression. 

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. 

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/... 

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