Transaminase mitochondrial

GABA transaminase is a mitochondrial enzyme which, like GAD, requires pyridoxal phosphate as co-factor. It is present in both neurons and glia and while secondary to... 

This pyridoxal-phosphate-dependent enzyme [EC 2.6.1.5], also known as tyrosine transaminase, catalyzes the reaction of L-tyrosine with a-ketoglutarate (or, 2-oxoglutarate) to produce 4-hydroxyphenylpyruvate and L-glutamate. L-Phenylalanine can act as the substrate instead of tyrosine. In some systems, the mitochondrial enzyme may be identical with aspartate aminotransferase. 

Transaminases participate in metabolism of most of the amino acids, over 60 different enzymes have been identified.142163 Best studied are the aspartate aminotransferases, a pair of cytosolic and mitochondrial isoenzymes which can be isolated readily from animal hearts. Their presence in heart muscle and brain in high concentration is thought to be a result of their functioning in the malate-aspartate shuttle... 

The twins were referred subsequently to a metabolic specialist because of the suspicion of an inborn error of metabolism. Biochemical testing revealed each had a hyperchloremic (increased blood chloride concentration) metabolic acidosis that was more profound in Elizabeth. Serum levels of glucose and liver transaminases were normal. Urinary organic acids revealed modestly increased concentrations of lactate and ketone bodies. Blood samples and fibroblasts from skin biopsies from both girls were sent to an established diagnostic laboratory for genetic mitochondrial diseases. Tests of respiratory chain complex enzymatic activities were normal. 

The spread of the damaging processes to adjacent hepatocytes is signalled by an increase in transaminase activity the liver cell membranes are also affected. The result is an enhanced release of cytoplasmic enzymes (GPT, to a lesser extent also GOT) into the serum. Ultimately, cell necrosis must be expected with a rise in mitochondrial enzymes in the serum (GDH, mGOT). From the point of view of biochemistry, the term hepatitis presupposes an increase in indicator enzymes once when the hepatocytes have been damaged or destroyed, (s. pp 93-95) (s. tabs. 5.3-5.5)... 

Transaminases are widely distributed throughout the body. AST is found primarily in the heart, liver, skeletal muscle, and Iddney, whereas ALT is found primarily in the liver and kidney, with lesser amounts in heart and skeletal muscle (Table 21-2). ALT is exclusively cytoplasmic both mitochondrial and cytoplasmic forms of AST are found in cells. These are genetically distinct isoenzymes with a dimeric structure composed of two identical polypeptide subunits of about 400 amino acid residues. 

Inagaki N, Kamisaki Y, Kiyama H, Horio Y, Tohyama M, Wada H (1985) Immunocytochemical localizations of cytosolic and mitochondrial glutamic oxaloacetic transaminase isozymes in rat retina as markers for the glutamate-aspartate neuronal system. Brain Res 325 336-339. 

GOTs = sarcoplasmic GOT isozyme GOTm — mitochondrial GOT isozyme GPT = glutamic pyruvic transaminase (alanine aminotransferase) MK = myokinase (adenylate kinase) p.m. = post mortem... 

Glutamate-Oxaloacetate Transaminase Origin pig heart (mitochondrial) Roche Diagnostics Glutamate-Oxaloacetate Transaminase (GOT)... 

The metabolic steps in gluconeogenesis occur in two intracellular compartments (Fig. 3.2) the cytosol and the mitochondrial matrix. The enzymes of the tricarboxylic acid cycle reside in the mitochondrial matrix, apart from succinate dehydrogenase which is present in the inner mitochondrial membrane, whereas most of the enzymes of the gluconeogenic pathway are present in the cytosol. Transaminases, such as alanine aminotransferase and aspartate aminotransferase, are present both in mitochondria and cytosol of the domestic fowl liver (Sarkar, 1977). One of the control enzymes in gluconeogenesis, PEPCK, has a different intracellular distribution in avian liver compared with mammalian liver (Table 3.3). PEPCK in both pigeon and domestic fowl liver is present almost exclusively (> 99%) in mitochondria (Soling et al.. 1973), whereas in most mammals that have been studied, it is present mainly in the cytosol, and only present, if at all, in smaller amounts in... 

Beyond individual considerations of the involvanent of certain hepatic transporters, like BSEP, and mitochondrial dysfunction on DILI, it is important to consider why these two risk factors can contribute so much to the manifestation of severe DILI in humans (Aleo et al., 2014). Bile acids, in general, appear to represent a more reliable marker of hepatic dysfunction regarding excretory abnormalities than serum bilirubin. Elevations in total bile acids can precede evidence of liver damage (as diagnosed by serum transaminase and bilirubin elevations) caused by hepatotoxic drugs by upward of 1 week (Fattinger et al., 2001). In order to explain this association, it is important to understand the intricate interactions between mitochondrial bioenergetics and transporter function within the liver. 

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