Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Holotyrosine phenol-lyase (EC 4.1.99.2), a pyridoxal-5'-phosphate (PLP)- requiring enzyme, was shown to rapidly dissociate when injected into BDF1 mice. The holoenzyme dissociated when incubated in plasma but not 0.01 M potassium phosphate (pH 7.4) buffer at 37 degrees C. A nonspecific alkaline phosphatase from calf intestine was found to inactivate the holoenzyme at pH 7.4 and 37 degrees C. This inactivation was inhibited in the presence of 0.5 M potassium phosphate buffer. Two other PLP-requiring enzymes, aspartate aminotransferase (EC 2.6.1.1), and alanine aminotransferase (EC 2.6.1.2) were inactivated by alkaline phosphatase in a similar manner. Incubation of holotyrosine phenol-lyase in the presence of bovine serum albumin also resulted in a reduction of holoenzyme activity but partially protected the enzyme from inactivation by alkaline phosphatase. A nuclear fraction having PLP-hydrolyzing activity also inactivated holotyrosine phenol-lyase. A regulatory function for alkaline phosphatase in the metabolism of PLP-requiring enzymes is suggested by these data.
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PMID:Albumin and alkaline phosphatase as factors involved in the regulation of tyrosine phenol-lyase activity. 65 5

The polymerase chain reaction with prior reverse transcription of RNA into cDNA was applied to hepatitis C virus RNA detection in human serum samples of different origin. In order to eliminate false negative results, the following steps were optimized: RNA extraction, reverse transcription, and oligonucleotide primer selection. We compared different RNA extraction methods using guanidinium salt/detergent and proteinase K digestion/phenol extraction, and tested virus particle enrichment with polyethylene glycol precipitation and ultracentrifugation. RNA extraction with guanidinium salt/detergent was the most efficient method. Ultracentrifugation of single samples did not improve hepatitis C virus RNA detection. Polyethylene glycol precipitation performed poorly. Recombinant thermostable reverse transcriptase produced cDNA from fewer samples than did Moloney murine leukaemia virus reverse transcriptase. Nested oligonucleotide primers from the 5'-terminal non-coding region of the hepatitis C virus genome amplified cDNA from more samples than did primers from the coding regions. Thirty six anti-hepatitis C virus antibody positive samples were tested; nested primers (nucleotides 6 to 327 and 15 to 288) yielded 21 amplificates, whereas primers from the coding region produced 16 amplificates (nucleotides 4684-5276) and 5 amplificates (nucleotides 5166-5270), respectively. The most efficient combination of steps was RNA extraction with guanidinium salt solution, reverse transcription with Moloney murine leukaemia virus reverse transcriptase and nested polymerase chain reaction primed with primers from the 5'-terminal non-coding region of the hepatitis C virus genome. Other combinations produced more false negative results. Three different groups of anti-hepatitis C virus antibody positive individuals had markedly different viraemia patterns: Hepatitis C virus RNA was detected in the sera of only 10% of anti-hepatitis C virus antibody positive blood donors, but in 90% of anti-hepatitis C virus antibody positive patients with clinically manifest hepatitis C, and 90% of anti-hepatitis C virus antibody positive haemophiliacs who had received plasma products in the past which had not been virus-inactivated. No hepatitis C virus RNA could be detected in the sera of 450 anti-hepatitis C virus antibody negative blood donors with elevated serum alanine aminotransferase catalytic concentrations.
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PMID:Improved detection of hepatitis C virus RNA by reverse transcription and polymerase chain reaction. 128 41

Biochemical and metabolic indicators were monitored in a group of volunteers suffering from a variety of chronic illnesses participating in a week's course on a special uncooked vegetable diet, known as "living food". Unmatched healthy controls ate the same diet cooked for 2 min in a microwave oven. After 1 week on the regimen, serum protein and urea contents decreased and alanine aminotransferase (ALAT) activity increased in both groups, although all within the normal range. Blood glucose increased in both groups to slightly above normal limits but total serum cholesterol dropped about 1 mmol/l from normal starting levels. Serum tocopherol and retinol increased only in the group eating the uncooked diet. In both groups urinary sodium dropped drastically without a significant change in potassium. Serum and urinary phenol and p-cresol diminished also significantly. It is concluded that this vegetable diet may be of some benefit in the short term but any longer-term use requires evaluation.
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PMID:Effects of eating an uncooked vegetable diet for 1 week. 148 62

The effects of phenol, guaiacol and m-cresol on erythrocytes, hepatocytes, dipalmitoyl phosphatidylcholine (DPPC)-liposomes and surface tension were studied at various concentrations. Phenol at 10 mM caused a slight inhibition of hypotonic hemolysis in rat erythrocytes. Guaiacol at 4 and 10 mM and m-cresol at 0.6 to 10 mM caused a significant inhibition of hypotonic hemolysis. In the enzyme leakage from isolated rat hepatocytes, phenol at 0.001 to 0.4 mM and 2 to 10 mM, guaiacol at 2 to 10 mM and m-cresol at 0.001 to 4 mM caused an inhibition in GOT leakage. The leakage of GPT from hepatocytes was inhibited by phenol at 0.4 to 10 mM, guaiacol at 2 to 10 mM, and m-cresol at 0.001 to 4 mM. m-Cresol at 10 mM caused increases in GOT and GPT leakage. The inhibition of phenol and m-cresol on the LDH leakage in hepatocytes were observed at a concentration of 0.001 mM and 0.1 to 1 mM, respectively. Guaiacol or m-cresol at 10 mM caused an increase in LDH leakage. Phase-transition temperature of DPPC-liposomes was depressed by phenol and m-cresol at 1 to 10 mM and by guaiacol at 5 and 10 mM. Guaiacol at 1 and 10 mM and m-cresol at 10 mM caused a depression of surface tension, but phenol caused no change in surface tension. The order of effects on erythrocyte, hepatocyte and DPPC-liposome membranes was m-cresol greater than phenol greater than or equal to guaiacol. In the present study, phenol and its related compound showed a positive correlation between their effects on various membranes and germicidal effects as evaluated by the phenol coefficient, but the effects were not related to a depression of surface tension.
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PMID:[Effects of phenol and related compounds on erythrocytes and hepatocytes from rats and dipalmitoyl phosphatidylcholine-liposomes]. 360 69

Animal experiments conducted in the late 1960s and early 1970s in various institutes of China showed that the effective antifertility agent in crude cottonseed oil was gossypol. Gossypol is a yellow substance which occurs in various parts of the cotton plant; its chemical structure is naphthol phenol. At the Capital Hospital gossypol was tested on 172 volunteers selected from hospital employees and workers from a nearby factory. All of the volunteers were under age 50, married and healthy with at least 1 child. Examinations required before treatment were general physical examination, a blood and urine analysis, an electrocardiogram, serum potassium concentration and serum analysis. 2 stages of gossypol treatment were required in the clinical study: the initial stage, the loading period, is of about 60 days. A daily dose of 20 mg gossypol was given successively for 60 days causing the sperms to become immotile, reduced in number or totally absent. A sperm count below 4 million/ml semen was considered to indicate infertility. The dosage in the 2nd stage, the maintenance period, was reduced to 1/3 of the original dose to maintain infertility. The volunteers were followed up every 2-3 months. Fatigue, decrease of libido and impaired appetite were the 3 main complaints. Serum glutamic-pyruvic transaminase (SGPT) activities showed that the transient symptoms of fatigue and loss of appetite were not related to disturbance of liver function. The mechanism of hypokalemia induced by gossypol is probably of renal origin. Infertility induced by gossypol in contraceptive doses over a relatively short period of administration was reversed about 3 months after stopping treatment. Gossypol used as a male antifertility agent has been found to be very effective and relatively safe.
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PMID:Clinical study of gossypol as a male contraceptive. 679 20

Investigation by polymerase chain reaction of HBV-DNA in serum from chronic hepatitis B virus carriers is not widely used for routine diagnosis because polymerase chain reaction assays are complex and may be too sensitive. We investigated the sensitivity, the specificity and the possible value for clinical use of a simplified polymerase chain reaction method in which a single, 30 cycles round of polymerase chain reaction is performed using only 10 microliters of serum treated with microwaves. The efficiency of the polymerase chain reaction in amplifying HBV-DNA was greater after microwave irradiation of serum than after alkaline extraction, but lower than after protein digestion and phenol chloroform precipitation. Despite its simplicity and high sensitivity, the assay was very specific. Studies in anti-HBe positive chronic hepatitis B virus carriers demonstrated HBV-DNA sequences in 1/15 (7%) healthy carriers, in 4/20 (20%) patients with slight alanine aminotransferase elevation, in 16/18 (89%) with marked alanine aminotransferase elevation and in all 20 with fluctuating alanine aminotransferase levels. In the latter, HBV-DNA was detected either at exacerbation (two cases), during remission (one case) or both (17 cases). HBV-DNA was detected by classical dot-blot hybridization in only 24/58 (41%) samples that were positive by the simplified polymerase chain reaction method. Although extremely high sensitivity is not achieved, microwave irradiation of serum simplifies considerably the detection of small amounts of HBV-DNA and makes polymerase chain reaction suitable for monitoring patients in whom weak hepatitis B virus replication is associated with ongoing liver disease.
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PMID:Microwave treatment of serum facilitates detection of hepatitis B virus DNA by the polymerase chain reaction. Results of a study in anti-HBe positive chronic hepatitis B. 775 85

A combined preparation of liver extract and flavin adenin dinucleotide (FAD) (Adelavin) has been widely used in patients with chronic liver diseases in Japan. One milliliter of this agent contains 15 microliters of phenol-soluble phase of liver nucleic acid fraction and 10 mg of FAD. To examine the advantages of using this preparation in the elimination of hepatitis C virus (HCV) from patients with chronic hepatitis (CH)-C receiving interferon (IFN), 2 ml of this preparation was intravenously (n = 9) or intramuscularly (n = 8) administered daily for 5 days before 6 million units of IFN-alpha was intramuscularly injected once. Before and 48 hours after the injection of IFN, serum ALT, 2'5'-oligoadenylate synthetase (2'5-AS) activity, and HCV RNA levels were measured. The daily administration of this preparation alone for 5 days did not significantly change serum ALT, 2'5-AS activities, and HCV RNA levels. The 2'5-AS activities were significantly increased by IFN after the intravenous injection of this preparation (p < 0.01), while an injection of IFN alone of this dose did not change its activities (n = 10). HCV RNA levels were significantly decreased by IFN only after the administration of the preparation (intramuscular, p < 0.01; intravenous, p < 0.01). The effect of intravenous injection of this preparation was also elicited in patients with HCV genotype II and with HCV more than 10(5) copies/ml. These results suggest that this preparation may enhance the 2'5-AS production by IFN as a result of the increase in mitochondrial adenosin triphosphate production and may be a potent agent to enhance the anti-viral efficacy of IFN in patients with CH-C.
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PMID:Enhancing effect of the liver extract and flavin adenin dinucleotide mixture on anti-viral efficacy of interferon in patients with chronic hepatitis C. 888 68

Central neuropeptides play important roles in many instances of physiological and pathophysiological regulation mediated through the autonomic nervous system. In regard to the hepatobiliary system, several neuropeptides act in the brain to regulate bile secretion, hepatic blood flow, and hepatic proliferation. Stressors and sympathetic nerve activation are reported to exacerbate experimental liver injury. Some stressors are known to stimulate corticotropin-releasing factor (CRF) synthesis in the central nervous system and induce activation of sympathetic nerves in animal models. The effect of intracisternal CRF on carbon tetrachloride (CCl4)-induced acute liver injury was examined in rats. Intracisternal injection of CRF dose dependently enhanced elevation of the serum alanine aminotransferase (ALT) level induced by CCl4. Elevations of serum aspartate aminotransferase, alkaline phosphatase, and total bilirubin levels by CCl4 were also enhanced by intracisternal CRF injection. Intracisternal injection of CRF also aggravated CCl4-induced hepatic histological changes. Intracisternal CRF injection alone did not modify the serum ALT level. Intravenous administration of CRF did not influence CCl4-induced acute liver injury. The aggravating effect of central CRF on CCl4-induced acute liver injury was abolished by denervation of hepatic plexus with phenol and by denervation of noradrenergic fibers with 6-hydroxydopamine treatment but not by hepatic branch vagotomy or atropine treatment. These results suggest that CRF acts in the brain to exacerbate acute liver injury through the sympathetic-noradrenergic pathways.
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PMID:Effect of central corticotropin-releasing factor on carbon tetrachloride-induced acute liver injury in rats. 1007 38

The protective action of thymol (paramethyl-isopropyl-phenol) was investigated against carbon tetrachloride (CCl(4))-induced hepatotoxicity in male Swiss albino mice. The CCl(4)at a dose of 20 microl kg(-1)produced damage to liver cells and was followed by the significant increase (P<0.001) in serum alanine aminotransferase (ALT) activity and hepatic lipid peroxidation after 24 h. The hepatocellular necrosis was further confirmed by histopathological examination of liver section. Oral administration of thymol in a single dose (300 mg kg(-1)) resulted in significant (P<0.05) amelioration of CCl(4)-induced hepatotoxicity. Thymol also inhibited lipid peroxidation induced by CCl(4)in vivo. The protection offered by thymol was also evident from histopathology photomicrograph. In a separate in vitro assay, thymol inhibited the non-enzymatic lipid peroxidation of normal mice liver homogenate induced by Fe(3+)-ascorbate. The present study suggests that thymol protects the liver against CCl(4)-induced toxicity and the protection may be mediated through its ability to inhibit lipid peroxidation. However, other interactions between thymol and CCl(4)remains to be elucidated. 1999 Academic Press.
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PMID:The protective action of thymol against carbon tetrachloride hepatotoxicity in mice. 1043 75

The protective effects of the juice of Opuntia ficus indica fruit (prickly pear) against carbon tetrachloride (CCl(4))-induced hepatotoxicity were examined in rats. The animals were treated orally with the juice (3 mL/rat) 2 h after administration of the hepatotoxic agent. Preventive effects were studied by giving the juice (3 mL/rat) for 9 consecutive days. On day 9 the rats received the hepatotoxic agent. Morphological and biochemical evaluations were carried out 24, 48 and 72 h after induction of the hepatic damage. Data show that O. ficus indica fruit juice administration exerts protective and curative effects against the CCl(4)-induced degenerative process in rat liver. Histology evaluation revealed a normal hepatic parenchyma at 48 h; the injury was fully restored after 72 h. Moreover, a significant reduction in CCl(4)-induced increase of GOT and GPT plasma levels is evident; these data are in agreement with the functional improvement of hepatocytes. O. ficus indica fruit juice contains many phenol compounds, ascorbic acid, betalains, betacyanins, and a flavonoid fraction, which consists mainly of rutin and isorhamnetin derivatives. Hepatoprotection may be related to the flavonoid fraction of the juice, but other compounds, such as vitamin C and betalains could, synergistically, counteract many degenerative processes by means of their antioxidant activity.
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PMID:Opuntia ficus indica (L.) Mill. fruit juice protects liver from carbon tetrachloride-induced injury. 1622 May 74


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