Enzyme regulation isozymes

Specialized controls Enzyme regulation is an important matter to cells, and evolution has provided a variety of additional options, including zymogens, isozymes, and modulator proteins. 

The reactions catalyzed by aspartokinase (1) and aspartate semialdehyde dehydrogenase (2) are utilized for the synthesis of all pathway products, including threonine. Regulation of aspartokinase activity is, therefore, considered to be of central importance in the overall control of the pathway. Two classes of differentially regulated isozymes of aspartokinase have been isolated from plants. One class is comprised of enzymes subject to feedback inhibition by threonine the other encompasses those inhibited by lysine, or by lysine and 5 -adenosylmethionine. Examples of each class have been isolated from several... 

PKC is a family of enzymes whose members play central roles in transducing information from external stimuli to cellular responses. Members of this family of serine/ threonine kinases respond to signals that cause lipid hydrolysis. PKC isozymes phosphorylate an abundance of substrates, leading to both short-term cellular responses such as regulation of membrane transport and long-term responses such as memory and learning. 

Adenylate kinase (AK) is a ubiquitous monomeric enzyme that catalyzes the interconversion of AMP, ADP, and ATP. This interconversion of the adenine nucleotides seems to be of particular importance in regulating the equilibrium of adenine nucleotides in tissues, especially in red blood cells. AK has three isozymes (AK 1,2, and 3). AK 1 is present in the cytosol of skeletal muscle, brain, and red blood cells, and AK 2 is found in the intermembrane space of mitochondria of liver, kidney, spleen, and heart. AK 3, also called GTP AMP phosphotransferase, exists in the mitochondrial matrix of liver and heart. 

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]. 

There is no experimental evidence adequate to evaluate whether metabolism of M-hcxanc is different in children. Similarly, there is no information available from animal experiments. The initial step in -hexane metabolism in animals is a hydroxylation step catalyzed by a P-450 enzyme. Since some of these enzymes are developmentally regulated, it would be of interest to know (1) if there are specific P-450 isozymes involved in -hexane hydroxylation and, (2) if so, are these isozymes known to be developmentally regulated ... 

In addition to CYP3A isozymes, PXR has also been shown to regulate other CYP enzymes, including CYP2B6 [12-14], CYP2B9 [15], CYP2C8 [16] and CYP2C9 [15],... 

The control via activation or inhibition of the rate(s) of an enzyme-catalyzed reaction(s). This control includes the increase or decrease in the stability or half-life of the enzyme(s). There are many different means by which control can be achieved. These include 1. Substrate availability and reaction conditions (e.g., pH, temperature, ionic strength, lipid interface activation) 2. Magnitude of Vraax sud valucs) 3. Activation (particularly, feedforward activation) 4. Isozyme formation 5. Com-partmentalization and channeling 6. Oligomerization/ polymerization 7. Feedback inhibition and cooperativity (particularly, allosterism and/or hysteresis) 8. Covalent modification and 9. Gene regulation (induction repression)... 

Thus in some cases, enzyme expression is directly influenced in a particular organ by testosterone or estrogens. For example, in the mouse kidney, testosterone directly regulates the expression of cytochrome P-450 isozymes, and this leads to the particular sensitivity of the female kidney to the nephrotoxicity of paracetamol. 

The second messenger molecules Ca2+ and cyclic AMP (cAMP) provide major routes for controlling cellular functions. In many instances, calcium (Ca2+) achieves its intracellular effects by binding to the receptor protein calmodulin. Calmodulin has the ability to associate with and modulate different proteins in a Ca2+-dependent and reversible manner. Calmodulin-dependent cyclic nucleotide phosphodiesterase (CaMPDE, EC 3.1.4.17) is one of the key enzymes involved in the complex interactions that occur between the cyclic-nucleotide and Ca2+ second messenger systems (see Figure 13.2). CaMPDE exists in different isozymic forms, which exhibit distinct molecular and catalytic properties. The differential expression and regulation of individual phosphodiesterase (PDE) isoenzymes in different tissues relates to their function in the body. 

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