Alanine transaminase

The initial enthusiasm for tacrine and velnacrine, which are the anticholinesterases most studied clinically, has been tempered by the fact that not all patients respond. Most show the peripheral parasympathomimetic effects of cholinesterase inhibition, e.g. dyspepsia and diarrhoea, as well as nausea and vomiting, and about half of the patients develop hepatotoxicity with elevated levels of plasma alanine transaminase. While some peripheral effects can be attenuated with antimuscarinics that do not enter the brain, these add further side-effects and the drop-out rate from such trials is high (<75%) in most long-term studies. Donepezil appears to show less hepatotoxicity but its long-term value remains to be determined. 

Interferon beta 1a (Rebif) 44 meg SQ Three times per week Flu-like symptoms 28% Injection site reactions 66% Leukopenia 22% Increased aspartate aminotransferase/ alanine transaminase 1 7-27%... 

Interferon beta 1b (Betaseron) 0.25 mg SQ Every other day Flu-like symptoms 60-76% Injection site reactions 50-85% Asthenia 49% Menstrual disorder 1 7% Leukopenia 1 0-1 6% Increased aspartate aminotransferase/ alanine transaminase 4-1 9%... 

ALT Alanine transaminase (SGPT) alanine creatine phospokinase... 

Elevated aspartate transaminase (AST), alanine transaminase (ALT), and /glutamyl transpeptidase (GGT)... 

Routine liver assessment tests include alkaline phosphatase, bilirubin, aspartate transaminase, alanine transaminase, and y-glutamyl transpeptidase (GGT). Additional markers of hepatic synthetic activity include albumin and prothrombin time. The substances are typically elevated in chronic inflammatory liver diseases such as hepatitis C, but may be normal in others with resolved infectious processes. 

The aminotransferases, aspartate transaminase and alanine transaminase, are enzymes that have increased concentrations in plasma following hepatocellular injury. The highest concentrations are seen in acute viral infections, or ischemic or toxic liver injury. 

FIGURE 21-1. Interpretation of liver function tests. (ALT, alanine transaminase AST, aspartate transaminase CT, computed tomography DDX, differential diagnosis GGT, y-glutamyl transpeptidase.)... 

Mild elevations of serum bilirubin, /globulin, and hepatic transaminase (alanine transaminase and aspartate transaminase) values to about twice normal in acute anicteric disease. 

Several factors correlate with improved response to IFN therapy, including increased alanine transaminases and HBV DNA levels, high histologic activity score at biopsy, and being non-Asian. Treatment for a minimum of 12 months is associated with greater sustained virologic response rates than treatment for 4 to 6 months. Conventional IFN therapy has been... 

Treatment for HCV infection is necessary because a high percentage of acutely infected patients develop chronic infections. Treatment is indicated in patients previously untreated who have chronic HCV, circulating HCV RNA, increased alanine transaminases levels, evidence on biopsy of moderate to severe hepatic grade and stage, and compensated liver disease. 

Patients should have blood urea nitrogen, serum creatinine, aspartate transaminase or alanine transaminase, and a complete blood count determined at baseline and periodically, depending on the presence of other factors that may increase the likelihood of toxicity (advanced age, alcohol abuse, and possibly pregnancy). Hepatotoxicity should be suspected in patients whose transaminases exceed five times the upper limit of normal or whose total bilirubin exceeds 3 mg/dL. At this point, the offending agent(s) should be discontinued, and alternatives selected. 

As examples, two enzymes that will be discussed again later in this chapter are alanine transaminase (alanine aminotransferase) and aspartate transaminase (aspartate aminotransferase). In both cases, the amino group is transferred to 2-oxoglutarate (also known as a-ketoglutarate), which is oxoacid, above, forming glutamate as amino acid2. For example, the alanine transaminase (ALT) reaction is ... 

For example, coupling alanine transamination (via ALT) with GLDH is shown in Figure 6.6b. A similar scheme can be drawn using, for example, aspartate transaminase in place of alanine transaminase. 

Transamination of alanine yields pyruvate catalysed by alanine transaminase (ALT) whilst aspartate produces oxaloacetate catalysed by aspartate transaminase (AST). All transaminase enzymes operate close to a true equilibrium (K eq 1, see Chapter 2) and... 

Determination of the level of cytosolic enzymes such as aspartate transaminase, alanine transaminase, and lactate dehydrogenase is part of standard biochemical liver function tests to measure hepatocellular necrosis [2, 101]. Cytosolic enzymes are not subject to genetic variations inherent in microsomal enzyme production. Liver cytosolic enzymes metabolize several molecules, of which galactose and amino acids are typical examples, used for hepatic function tests. 

This enzyme [EC 2.6.1.2], also known as glutamic-pyruvic transaminase and glutamic-alanine transaminase, catalyzes the pyridoxal-phosphate-dependent reaction of alanine with 2-ketoglutarate, resulting on the production of pyruvate and glutamate. 2-Aminobutanoate will also react, albeit slowly. There is another alanine aminotransferase [EC 2.6.1.12], better known as alanine-oxo-acid aminotransferase, which catalyzes the pyridoxal-phosphate-dependent reaction of alanine and a 2-keto acid to generate pyruvate and an amino acid. See also Alanine Glyoxylate Aminotransferase... 

Schor DS, Struys EA, Hogema BM, Gibson KM, Jakobs C (2001) Development of a stable-isotope dilution assay for gamma-aminobutyric acid (GABA) transaminase in isolated leukocytes and evidence that GABA and beta-alanine transaminases are identical. Clin Chem 47 525-531... 

ALT alanine transaminase alanine aminotransferase previously known as SGPT (serum glutamate pyruvate transaminase). 

In a retrospective review of 497 patients taking propylthiouracil for hyperthyroidism, clinically overt hepatitis developed in six patients at 12-49 days after starting the drug (50). Jaundice and itching were present in five, fever in two, rash in two, and arthralgia in one. Serum bilirubin, alanine transaminase, and alkaline phosphatase were increased in five, four, and six patients respectively. The type of hepatic injury was cholestatic in three, hepatocellular in one, and mixed in two. There were no differences in age, sex, drug dose, or serum thyroid hormone concentrations at time of diagnosis in those with hepatic injury compared with those without. Liver function normalized in all patients at 16-145 days after withdrawal of propylthiouracil. In addition to these cases of overt liver injury, 14% of the cohort had mild asymptomatic liver enzyme rises at a mean of 75 days after the start of treatment. 

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. 

Another patient taking acarbose also had a serum alanine transaminase three times the upper limit of the reference range, but she had positive serology for hepatitis A (21). 

In a 56-week study there was an association between the dose of acarbose in the range 50-300 mg tds and the development of abnormal liver function in 359 patients with type 1 (21%) and type 2 diabetes (38). The patients took the maximum tolerated dose, and 30% took doses of 100 mg or less. Of the patents who were randomized to acarbose (n = 240), 8% developed abnormal liver function tests (alanine transaminase activity more than three times the upper limit of normal) compared with 1% of those who took placebo (n — 119). The dose of acarbose was 200-300 mg tds in those who developed abnormal liver function. Liver function recovered promptly on withdrawal. 

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