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At least 235 records · Page 13Linked to original sources
PubMed1986

Induction of L-alanine:4,5-dioxovalerate transaminase by phenylhydrazine is associated with depletion of heme level.

The hemin regulation of L-alanine:4,5-dioxovalerate transaminase, the enzyme proposed for an alternate route of delta-aminolevulinic acid (ALA) biosynthesis in mammalian system was studied in different conditions: phenylhydrazine induced anemia, polycythemia by erythropoietin to anemic rats, treatment with cobalt chloride, a porphyrogenic drug. The activity of L- alanine:4,5-dioxovalerate transaminase in liver and kidney is stimulated in phenylhydrazine, whereas, erythropoietin injection to anemic rats prevents such stimulation. Further treatment with cobalt chloride to erythropoietin treated anemic rats stimulates the enzyme activity. Actinomycin D, however, inhibits the stimulation of L-alanine:4,5-dioxovalerate transaminase by phenylhydrazine suggesting that induction is at the level of transcription. Induced level of this enzyme in anemic condition was estimated quantitatively by radial immunodiffusion using antibody raised against L-alanine:4,5-dioxovalerate transaminase. Moreover, our studies reveal that stimulation of L-alanine:4,5-dioxovalerate transaminase in anemic condition is dependent on depletion of heme level. The regulatory role of intracellular heme pool on the induction of this enzyme suggests its physiological importance in heme biosynthesis.

Anemia↗
PubMed1986

Excess generation of endogenous heme inhibits L-alanine:4,5-dioxovalerate transaminase in rat liver mitochondria.

In the present study, we examined the possibility that the excess heme generation within mitochondria may provide a local concentration, sufficient to inhibit the activity of L-alanine:4,5-dioxovalerate transaminase, the enzyme proposed for an alternate route of delta-aminolevulinic acid biosynthesis in mammalian system. This was accomplished by assaying together L-alanine:4,5-dioxovalerate transaminase and heme synthetase activities in intact mitochondria isolated from rat liver. Endogenous heme in intact mitochondria has been generated in excess, by increasing the concentration of the substrate of heme synthetase. Our studies showed that the activity of L-alanine:4,5-dioxovalerate transaminase decreased as the rate of heme formation increased. In intact mitochondria, almost 50% inhibition of alanine:4,5-dioxovalerate transaminase was obtained with 4.0 mumole of heme generation. We conclude that end product inhibition of L-alanine:4,5-dioxovalerate transaminase by hemin, which was proposed in earlier report by us (FEBS Letter (1985), 189, 129), is an important physiological mechanism for the regulation of hepatic heme biosynthesis.

Animals↗
PubMed1999

Effects of increasing doses of vigabatrin on platelet gamma-aminobutyric acid-transaminase and brain gamma-aminobutyric acid in rats.

We report the relationship of GABA-transaminase inhibition in platelets and brain with the increase in brain gamma-aminobutyric acid (GABA), as percents of the control, at 24 h after single and after 3 and 8 days of treatment with increasing doses (1, 3, 10, 30, 100 and 300 mg kg(-1) day(-1) of vigabatrin in rats. The inhibition of GABA-transaminase in platelets correlated at least as well as that in brain with the increase in brain GABA after 3 days (r = - 0.87 vs. r = -0.78), and 8 days of treatment (r = -0.77 vs. r = -0.74), and when the data of single and multiple doses were pooled (r = -0.77 vs. r = -0.75). The correlation between platelet GABA-transaminase and brain GABA fitted to a power curve, the increase in brain GABA being significant only when platelet GABA-transaminase was inhibited to less than 50% of the control. Our results suggest that platelet GABA-transaminase could be a peripheral marker of the effect of vigabatrin on brain GABA in rats.

4-Aminobutyrate Transaminase↗
PubMed2003

Caloric restriction increases gluconeogenic and transaminase enzyme activities in mouse liver.

Long-term caloric restriction (CR) has been shown to extend maximum life span in laboratory rodents. We investigated the activities of gluconeogenic and transaminase enzymes in the livers of old and young mice fed either control or calorie-restricted diets. Livers were sampled 48 h after the last scheduled feeding time. Old mice on CR showed significant increases in the activities of pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase and glucose-6-phosphatase when compared with controls, indicating increased gluconeogenesis. Increased activities of tyrosine, tryptophan, histidine, phenylalanine, alanine and aspartate transaminases, as well as of malate and glutamate dehydrogenases were also observed, while branched-chain amino acid transaminase was unchanged. Young mice on CR showed a significant increase only in the phosphoenolpyruvate carboxykinase activity in the gluconeogenic pathway, while transaminases were increased significantly, except for tryptophan and branched-chain amino acid transaminases. Glutamate dehydrogenase also showed increased activity but malate dehydrogenase was unchanged. Increases in the level of acetyl-CoA and [Acetyl-CoA]/[CoA] ratio were observed only in the old CR mice. Our results demonstrate increased gluconeogenic activity in CR mice and are consistent with a state of increased hepatic gluconeogenesis and protein turnover during CR.

Acetyl Coenzyme A↗
PubMed2001

Effects of the antidepressant/antipanic drug phenelzine on alanine and alanine transaminase in rat brain.

1. Phenelzine (PLZ) is an antidepressant with anxiolytic properties. Acute and chronic PLZ administration increase brain GABA levels, an effect due, at least in part, to an inhibition of the activity of the GABA metabolizing enzyme, GABA transaminase (GABA-T). 2. Previous preliminary reports have indicated that acute PLZ treatment also elevates brain alanine levels. As with GABA, the metabolism of alanine involves a pyridoxal phosphate-dependent transaminase. 3. In the study reported here, the effects of acute PLZ treatment on the levels of various amino acids, some of which are also metabolized by pyridoxal phosphate-dependent transaminases were compared in rat whole brain. Of the 6 amino acids investigated, only GABA and alanine levels were elevated (in a time- and dose-dependent manner). 4. The elevation in brain alanine levels could be explained, at least in part, by a time- and dose-dependent inhibitory effect of PLZ on alanine transaminase (ALA-T), although as with GABA the increases are higher than expected from the degree of enzyme inhibition produced. In addition, we also showed that the elevation in alanine levels and the inhibition of alanine transaminase in the brain are retained after 14 days of PLZ treatment, and that PLZ produces a marked increase in extracellular levels of alanine. 5. These results are discussed in terms of their relevance to synaptic function and to the pharmacological profile of PLZ.

Alanine↗
PubMed2000

Serial measurements of serum transaminases in renal transplant recipients with chronic hepatitis C: do they reflect disease severity?

UNLABELLED: Chronic hepatitis C infection is a common problem in renal allograft recipients, this study was designed to investigate the association of serum aminotransferase levels with liver histology, in renal transplant patients with chronic hepatitis C virus (HCV) infection, in the long term. METHODS: In this study, 82 HCV-infected renal allograft recipients, who were followed up with functioning grafts for at least 6 months, were analyzed. Patients were classified according to their transaminase values as persistently normal, intermittently abnormal, or continuously abnormal liver function tests. Serum transaminase levels exceeding at least 1.5 times the upper limit of normal (40 IU) for periods longer than 1 month were taken as abnormal. Patients with abnormal liver function tests owing to HCV unrelated causes (drugs, alcohol, or other toxic substances, other viruses, etc.) were excluded from the study. Forty-eight of these patients underwent at least one liver biopsy. RESULTS: Of the 82 patients, 34 (41.5%) had persistently normal (liver biopsy revealed normal or minimal changes in 77.0%, chronic persistent hepatitis in 15.3%, chronic active hepatitis in 7.7%; no patient had cirrhosis), 29 (35.3%) intermittently abnormal (liver histology was consistent with minimal changes in 50%, chronic persistent hepatitis in 27.8%, chronic active hepatitis in 16.7%, cirrhosis in 5.5%), 19 (23.2%) persistently abnormal (liver biopsy showed minimal changes in 41.1%, chronic persistent hepatitis in 17.6%, chronic active hepatitis in 35.3%, cirrhosis in 5.9%) transaminase values. CONCLUSION: Although continuously or intermittently elevated transaminases do not always indicate morphologically advanced disease, the normal course of serum transaminases is mostly accompanied by normal, or near-normal, liver histology, in HCV-infected renal transplant patients. Liver biopsy is not indicated in deciding disease severity in these patients unless clinical findings dictate otherwise.

Adolescent↗
PubMed2000

Human brain GABA transaminase tissue distribution and molecular expression.

Human brain gamma-aminobutyrate transaminase is differentially expressed in a tissue-specific manner. mRNA master dot-blot analysis for 50 different human tissues, including different brain regions and fetal tissues, provided a complete map of the tissue distribution. Genomic Southern analysis revealed that the gamma-aminobutyrate transaminase gene is a single copy, at least 15 kb in size. In addition, human brain gamma-aminobutyrate transaminase cDNA was expressed in Escherichia coli using a pGEX expression vector system. Catalytically active gamma-aminobutyrate transaminase was expressed in large quantities and the purified recombinant enzyme had kinetic parameters that were indistinguishable from those isolated from other mammalian brains. The human enzyme was inactivated by a well-known antiepileptic drug vigabatrin. Values of Ki and kinact were 1 mM and 0.35 min-1, respectively. Results from inactivation kinetics suggested that human gamma-aminobutyrate transaminase is more sensitive to the vigabatrin drug than the enzyme isolated from bovine brain.

4-Aminobutyrate Transaminase↗
PubMed1971

Central neural regulation by adrenergic nerves of the daily rhythm in hepatic tyrosine transaminase activity.

1. In adrenalectomized fasted rats transection of the spinal cord at C7-C8 or placement of bilateral electrolytic lesions in the lateral hypothalamus when performed in the morning interrupted the daily rhythm of hepatic tyrosine transaminase by elevating low (AM) enzyme activities to high (PM) levels; lesions placed in PM did not affect the late afternoon rise in enzyme activity.2. Bilateral thalamic lesions had no affect on enzyme activity.3. The activity of hepatic catechol-O-methyl transferase was unaffected by hypothalamic lesions.4. The lesion-evoked rise of tyrosine transaminase activity was abolished by exogenously administered norepinephrine.5. Cycloheximide blocked the rise of tyrosine transaminase activity caused by hypothalamic lesions.6. The results suggest that rhythmic activity of sympathetic nerves governed by lateral hypothalamus contribute to regulation of the daily rhythm in tyrosine transaminase by regulating the release of norepinephrine peripherally; norepinephrine may block the daily rise of enzyme by interfering with protein synthesis, possibly of new enzyme, by competing with pyridoxal co-factor.7. It is proposed that alternating activity of sympathetic-adrenergic and vagal-cholinergic nerves to liver, controlled by the C.N.S., contribute to rhythmic activity of hepatic tyrosine transaminase.

Adrenalectomy↗
PubMed1990

Stereospecific production of the herbicide phosphinothricin (glufosinate) by transamination: cloning, characterization, and overexpression of the gene encoding a phosphinothricin-specific transaminase from Escherichia coli.

We have cloned the gene encoding a 43-kilodalton transaminase from Escherichia coli K-12 with a specificity for L-phosphinothricin [L-homoalanine-4-yl-(methyl)phosphinic acid], the active ingredient of the herbicide Basta (Hoechst AG). The structural gene was isolated, together with its own promoter, and shown to be localized on a 1.6-kilobase DraI-BamHI fragment. The gene is subject to catabolite repression by glucose; however, repression could be relieved completely when 4-aminobutyrate (GABA) served as the sole nitrogen source. The regulation pattern obtained and a comparison of the restriction map of the initially cloned 15-kilobase SalI fragment with the physical map of the E. coli K-12 genome suggest that the cloned gene is identical with gabT, a locus on the gab gene cluster of E. coli K-12 which codes for the GABA:2-ketoglutartate transaminase (EC 2.6.1.19). A number of expression plasmids carrying the isolated transaminase gene were constructed. With these constructs, the transaminase expression in transformants of E. coli could be increased up to 80-fold compared with that in a wild-type control, and the transaminase constituted up to 20% of the total soluble protein of the bacteria. Thus, the protein crude extracts of the transformants could be used, after a simple heat precipitation step, for the biotechnological production of L-phosphinothricin in an enzyme reactor.

Aminobutyrates↗
PubMed1978

Effects of in vivo and in vitro dialysis on plasma transaminase activity.

The effects of dialysis on plasma glutamic oxalacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) were investigated. GOT was measured using Autoanalyzer (SMA) and kinetic (Karmen) methods. Hemodialysis of uremic subjects was associated with a significant increase of GOT (SMA) and GPT (SMA). In contrast, hemodialysis had no effect on GOT (Karmen). However, the SMA method is influenced by substances affecting the blank value. Therefore, the results suggest that the increase in transaminase activities measured by the SMA method are not due to true increases in enzyme activities. Plasma from dialysis patients, obtained prior to hemodialysis, was also dialyzed in vitro. In vitro dialysis of uremic plasma significantly increased GOT (SMA), GOT (Karmen) and GPT vitro dialysis of uremic plasma significantly increased GOT (SMA), OGT (Karmen) and GPT (SMA). The results suggest that an inhibitor of transaminase activity may accumulate in renal failure. In vitro dialysis may remove this inhibitor and thus increase true transaminase activity.

Alanine Transaminase↗
PubMed1990

Role of L-alanine: 4,5-dioxovalerate transaminase in chlorophyll synthesis in Bajra (Pennisetum typhoideum) seedlings.

L-alanine:4,5-dioxovalerate transaminase activity and chlorophyll levels were estimated in lead and mercury treated Bajra seedlings. The enzyme activity increased with age upto 2nd day of germination and decreased on consequent days, where as the chlorophyll content increased with age upto 4th day and remained constant on day 5. Both the metals have no effect on L-alanine: 4,5-dioxovalerate transaminase activity but reduced chlorophyll levels. In vitro incubation of the enzyme with metal solutions showed that the enzyme activity was inhibited by mercury, while lead had no effect. Studies on sub-cellular localization of the L-alanine:4,5-dioxovalerate transaminase showed that it is present in all fractions. The non-correlation between L-alanine: 4,5-dioxovalerate transaminase activity and chlorophyll synthesis is evident from different activity profiles with age and response to heavy metal treatment in the seedlings. Hence, our results suggest the non-involvement of L-alanine:4,5-dioxovalerate transaminase in chlorophyll synthesis in bajra seedlings.

Aminolevulinic Acid↗
PubMedDate not supplied

[The effect of hydrocortisone and insulin on the activity and isoenzymes of typrosine-alpha-ketoglutarate transaminase in the ctyostructures of the livers of rats of different ages].

Administration of hydrocortisone or insulin and also a simultaneous use of these hormones in a high dose caused a marked elevation of the total activity of tyrosine-alpha-ketoglutaric transaminase and its anode and cathode isoenzymes in the soluble fraction of the liver in the sexually immature (weighing 100-110 g) and mature (weighing 180-200 g) male rats. The stimulating effect of insulin was sharper in the young in comparison with adult animals. Administration of hydrocortisone caused a more pronounced elevation of the total tyrosine-alpha-ketoglutaric transaminase activity in the hepatic mitochondria of young rats than in adult animals. Insulin administration increased the activity of tyrosine-alpha-ketoglutaric transaminase in the mitochondria of the liver of the sexually mature male rats without significant changes of this enzyme in the sexually imature rats. A simultaneous injection of hydrocortisone and insulin to the sexaully mature male rats caused the same increase in the tyrosine-alpha-ketoglutaric transaminase activity in the hepatic mitochondria as after the administration of glucocorticosteriod alone. As to the sexaully immature males, the activity of the enzyme fell to the normal level. It is supposed that androgens played a significant role in the realization of the inducing action of glucocorticoids and insulin influencing the synthesis of tyrosine-alpha-ketoglutaric transaminase in different directions in the mitochondria of the liver of young and sexually mature animals.

Animals↗
PubMed1997

[Effect of methadone or naltrexone on the course of transaminases in parenteral drug users with hepatitis C virus infection].

A prospective study was conducted on the evolution of serum transaminases in 116 patients infected with hepatitis C virus (HCV), parenteral drug abusers, included for 6 months in treatment programs with methadone, naltrexone or "drug free" regimen. Treatment with methadone or naltrexone did not result in a transaminase increase in these patients. In contrast, patients included in the drug-free program appear to have a higher increase in serum transaminase levels than those treated with methadone or naltrexone (146.1 +/- 122.29 vs 91.88 +/- 81.96 and 86.99 +/- 64.26 Ul/ml, respectively). Such an increase originated mainly from patients who anytime during follow-up had a liver necrosis outbreak in the acute hepatitis range, and is offset if, instead of a given transaminase value, we consider a simplified liver necrosis index (1.28 +/- 0.74 vs 0.95 +/- 0.72 and 1.01 +/- 0.65, respectively; p > 0.05). HIV infected patients have serum transaminase values similar to those in HIV-negative patients (80.61 +/- 58.81 vs 113.63 +/- 99.59, respectively; p > 0.05).

Adult↗
PubMed1995

Liver histology in hepatitis C infection: a comparison between patients with persistently normal or abnormal transaminases.

Forty two cases of confirmed hepatitis C virus (HCV) infection with available liver histology were studied. Most patients, 23 of 42 (55%) had abnormal liver function tests but 19 of 42 (45%) had persistently normal liver transaminases (mean aspartate transaminase (AST) 24.1 IU/l, mean follow up 10 months). Histological examinations in the group with normal AST activities were normal in two of 19 (11%), showed non-specific reactive hepatitis in eight of 19 (42%), chronic persistent hepatitis in six of 19 (31%), and chronic active hepatitis in three of 19 (16%). Twenty three of 42 (55%) had either persistently or temporary raised liver transaminases (mean AST 96.2 IU/l, mean follow up 16 months). Histological examinations in this second group with abnormal liver biochemistry showed reactive hepatitis in five of 23 (22%), chronic persistent hepatitis in six of 23 (26%), chronic active hepatitis in 10 of 23 (43%), and cirrhosis in two (9%). Average alcohol intake was significantly higher in the group within abnormal liver function (17.8 v 6.4 units, p = 0.01). Although serious pathology was more frequent in the abnormal transaminase group, significant liver pathology (chronic persistent hepatitis or chronic active hepatitis) was found in nine of 19 (47%) of cases with repeatedly normal transaminases. Liver biopsy is advised in all cases of chronic hepatitis C infection to accurately assess both the degree of fibrosis and the current activity of the disease.

Adult↗
PubMed1975

[Studies On Glutamic Pyruvic- And Oxaloacetic Transaminase Of Different Organs Of Ascaris Lumbricoides Suis]

A Study on glutamic pyruvic and oxaloacetic transaminase of different organs(e.g intestine, seminal vesicle, reticular tissue, uterus, ovary, testes) in Ascaris lumbricoides suis have been investigated. The activity of transaminase were determined on the whole homogenates and subcellular fractions separated by differential centrifugation. The activity of glutamic pyruvic and oxaloacetic were assayed by colorimetric method of Reitman-Frankel. The results were obtained as follows: 1. About ninty percent of the glutamic pyruvic and oxaloacetic transaminase in different organs was found to be localized in the supernatant fraction with the separation of differential centrifugation. And it was found that ten percent of glutamic pyruvic and oxaloacetic transaminase exists in the mitochondrial fraction. 2. The specific activity of glutamic oxaloacetic transnaminase in different organs was relatively higher than the glutamic pyruvic transaminase activity.

Journal Article↗
PubMed1977

Raised serum transaminase levels in patients with rheumatic fever treated with salicylates.

Of 11 patients with acute rheumatic fever, 9 were treated with a total daily salicylate dosage of 3,6 g or less, 1 patient required a total daily dosage of 5,4 g and another required 9,0 g daily. Six of the 11 patients had elevated serum transaminase levels, and all were asymptomatic. The elevated transaminase levels appear to bear a direct relationship to the serum salicylate level, and a serum salicylate level of 19,2 mg/100 ml appears to be the critical point. In 5 out of the 6 patients with elevated transaminases, the serum salicylate level exceeded 19,2 mg/100 ml, while in the 5 patients with normal transaminases the serum salicylate level did not exceed 19,2 mg/100 ml. Also, in 10 of the 11 patients eosinophilia was noted, but this decreased despite continued or increased salicylate administration. A narrow margin thus appears to exist between therapeutic serum salicylate levels and hepatotoxic levels, and serial serum transaminase estimations are advocated in patients on long-term salicylate therapy.

Acute Disease↗
PubMed2003

Screening for statin-related toxicity: the yield of transaminase and creatine kinase measurements in a primary care setting.

BACKGROUND: Recommendations for monitoring levels of transaminases (alanine aminotransferase and aspartate aminotransferase) and of creatine kinase (CK) in patients taking 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) vary and are not based on data from clinical practice. We performed a study to determine the yield of routine screening of aminotransferase and CK levels among patients taking statins. METHODS: We performed a retrospective review of a primary care practice's computerized medical record. A computerized search identified all patients with a statin on their medication list and gave their alanine aminotransferase, aspartate aminotransferase, and CK values for 1998. We reviewed the records of all patients for whom these values were significantly or moderately abnormal to determine the values' relationship to statin therapy and outcomes. RESULTS: During the year of the study, 1014 (85%) of the 1194 patients who had a statin on their medication list had at least 1 monitoring test performed. Of these 1014 patients, 10 (1.0%) had a significant elevation and 5 (0.5%) a moderate elevation of transaminase levels, but none of these abnormalities appeared to be related to statin use. Moreover, 6 (0.9%) patients had at least 1 significantly abnormal CK value but it did not appear to be attributable to a statin; and of the 14 (2.1%) patients who had a moderate CK elevation, it was potentially due to a statin in only 2. There were no documented adverse sequelae associated with these abnormal results. CONCLUSIONS: In this study of statin use in a primary care practice, routine monitoring revealed no cases of significantly or moderately abnormal transaminase values attributable to statins. No significantly abnormal and only 2 moderately abnormal CK values were potentially attributable to statin use. This study questions the usefulness of routine measurement of transaminase and CK levels in all patients taking statins.

Alanine Transaminase↗
PubMed1995

Subclinical Addison's disease: a cause of persistent abnormalities in transaminase values.

A common reason for referring patients to hepatologists is persistently abnormal serum transaminase levels with vague constitutional symptoms. In the United Kingdom, these abnormalities are most often caused by a fatty liver either related to obesity or alcohol abuse; they are less commonly caused by chronic liver disease, particularly chronic viral hepatitis, autoimmune hepatitis, or chronic biliary disease. Endocrine disease is rarely a cause of these abnormalities, although hypothyroidism and hyperthyroidism are well-recognized causes. Addison's disease has been only reported once in the literature by R. G. Olsson as a cause of increased transaminase levels associated with constitutional symptoms; it is not mentioned in textbooks on hepatology. Three patients with Addison's disease are reported here, all of whom had increased serum transaminase levels for more than 6 months before the recognition of the hypoadrenalism with resolution to normal after steroid replacement. Hepatologists should consider subclinical Addison's disease as a cause of persistently increased transaminase levels with constitutional symptoms in the absence of evidence for fatty liver as well as viral and autoimmune markers.

Addison Disease↗