Isozymes known genes

Carbonic anhydrase (CA) exists in three known soluble forms in humans. All three isozymes (CA I, CA II, and CA III) are monomeric, zinc metalloenzymes with a molecular weight of approximately 29,000. The enzymes catalyze the reaction for the reversible hydration of C02. The CA I deficiency is known to cause renal tubular acidosis and nerve deafness. Deficiency of CA II produces osteopetrosis, renal tubular acidosis, and cerebral calcification. More than 40 CA II-defi-cient patients with a wide variety of ethnic origins have been reported. Both syndromes are autosomal recessive disorders. Enzymatic confirmation can be made by quantitating the CA I and CA II levels in red blood cells. Normally, CA I and CAII each contribute about 50% of the total activity, and the CAI activity is completely abolished by the addition of sodium iodide in the assay system (S22). The cDNA and genomic DNA for human CA I and II have been isolated and sequenced (B34, M33, V9). Structural gene mutations, such as missense mutation, nonsense... 

Several independent laboratories have now demonstrated that both lithium and valproate (VPA) exert complex, isozyme-specific effects on the PKC (protein kinase C) signaling cascade (reviewed in [3, 5, 11-13]). Not surprisingly, considerable research has recently attempted to identify changes in the activity of transcription factors known to be regulated (at least in part) by the PKC signaling pathway - in particular the activator protein 1 (AP-1) family of transcription factors. In the CNS, the genes that are regulated by AP-1 include those for various neuropeptides, neurotrophins, receptors, transcription factors, enzymes involved in neurotransmitter synthesis, and proteins that bind to cytoskeletal elements [14]. 

The structure of an enzyme can also vary within a person, since different genes may encode enzymes that catalyse the same reaction. These enzymes are known as isozymes. Isozymes are often specific for different types of tissue. For example, lactate dehydrogenase (LDH) is produced in two forms, the M-type (muscle) and the H-type (heart). The M-type is predominates in tissue subject to anaerobic conditions, such as skeletal muscle and liver tissue, whereas the H-type predominates in tissue under aerobic conditions, such as the heart. Isozymes may be used as a diagnostic aid. For example, the presence of H-type LDH in the blood indicates a heart attack, since heart attacks cause the death of heart muscle with the subsequent release of H-type LDH into the circulatory system. 

Summary of the gene nomenclature, accession numbers, common names, tissue distribution, and function, if known, for the human and mouse alkaline phosphatase isozymes... 

There are two major forms of SOD. In humans the Cu-Zn isoenzyme occurs in cytoplasm. A Mn-containing isozyme is found in the mitochondrial matrix. Lou Gehrig s disease, a fatal degenerative condition in which motor neurons are destroyed, is now known to be caused by a mutation in the gene that codes for the cytosolic Cu-Zn isozyme of SOD. 

The term isozyme was originally defined as meaning enzymes with a different primary structure, catalyzing the same reaction, encoded by different genes. However, the term is now used more broadly. Some isozymes are now known to arise from alternate splicing of pre-mRNA to form different mRNAs (mRNA is the final nucleic acid template used for protein synthesis.)... 

Cases are known, however, where Drosophila genes coding for one family of isozymes are linked. The classical example is the rudimentary locus (1-54.5). This locus contains genes which control the synthesis of the functionally related enzymes aspartate carbamyl transferase (ACT), carbamyl phosphate synthetase... 

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