Enzymes activity metabolic pathways regulation

Nucleotide levels apparently regulate CPS activity (O Neal and Naylor, 1968,1976 Ong and Jackson, 1972a,b Parker and Jackson, 1981). Pyrimidine nucleotides inhibit CPS while purine nucleotides (GMP, IMP) stimulate activity. Ornithine activated CPS and could overcome inhibition by pyrimidines whereas arginine did not affect the activity of CPS from any of these sources. Metabolic regulation of plant OCT has not been reported. Compartmentaliza-tion at the subcellular and tissue levels as well as developmental control are certainly important in the regulation of this key pathway. Molecular, biochemical, and immunological approaches will all be necessary to unravel the regulatory features of these key enzymes and metabolic pathways. 

In die metabolic pathway to an amino add several steps are involved. Each step is die result of an enzymatic activity. The key enzymatic activity (usually die first enzyme in the synthesis) is regulated by one of its products (usually die end product, eg die amino add). If die concentration of die amino add is too high die enzymatic activity is decreased by interaction of die inhibitor with the regulatory site of die enzyme (allosteric enzyme). This phenomenon is called feedback inhibition. 

Metabolic pathways are regulated by rapid mechanisms affecting the activity of existing enzymes, eg, allosteric and covalent modification (often in response to hormone action) and slow mechanisms affecting the synthesis of enzymes. 

There is no information on the metabolism of 3,3 -dichlorobenzidine in children. Limited data in humans suggest that N-acetylation is an important metabolic pathway (Belman et al. 1968), and a detoxification mechanism. N-Acetylation in humans is likely done by one of two families of N-acetyltransferases. One of these families, NAT2, is developmentally regulated (Leeder and Kearns 1997). Some enzyme activity can be detected in the fetus by the end of the first trimester. Almost all infants exhibit the slow acetylator phenotype between birth and 2 months of age. The adult phenotype distribution is reached by the age of 4-6 months, whereas adult activity is found by approximately 1-3 years of age. Also, UDP-glucurono-syltransferase, responsible for the formation of glucuronide conjugates, seems to achieve adult activity by 618 months of age (Leeder and Kearns 1997). These data suggest that metabolism of 3,3 -dichloro-benzidine by infants will differ from that in adults in extent, rate, or both. 

There are several ways by which TSH secretion can be increased. An increased hepatic enzyme activity may cause an increased metabolism of thyroid hormones, leading to lower semm hormone levels, which in mm leads to increased secretion of TRH, and subsequently increased TSH secretion. Regarding human relevance, the pathways for regulation of the hypothalamo-pituitary-thyroid axis of rats and humans are similar and the mechanism is relevant for humans, but the human system is far more resistant to perturbation. 

Metabolite flow along a metabolic pathway is mainly determined by the activities of the enzymes involved (see p. 88). To regulate the pathway, it is suf cient to change the activity of the enzyme that catalyzes the slowest step in the reaction chain. Most metabolic pathways have key enzymes of this type on which the regulatory mechanisms operate. The activity of key enzymes is regulated at three independent levels ... 

Finally, the activity of key enzymes can be regulated by ligands (substrates, products, coenzymes, or other effectors), which as allosteric effectors do not bind at the active center itself, but at another site in the enzyme, thereby modulating enzyme activity (6 see p. 116). Key enzymes are often inhibited by immediate reaction products, by end products of the reaction chain concerned feedback inhibition), or by metabolites from completely different metabolic pathways. The precursors for a reaction chain can stimulate their own utilization through enzyme activation. 

Preiss, J. and Kosuge, T. 1976. Regulation of enzyme activity in metabolic pathways. In Plant Biochemistry. Third Edition (Bonner, J. and Varner, J. E., eds), pp. 277-336. New York - London Academic Press. 

For the regulation of metabolic pathways metabolites are often used which are a product of that pathway. The basic strategy for the regulation is exemplified in the mechanisms employed in the biosynthetic and degradation pathways of amino acids, purines, pyrimidines, as well as in glycolysis. In most cases a metabolite (or similar molecule) of the pathway is utilized as the effector for the activation or inhibition of enzymes in that pathway. 

The current state of Ser/Thr phosphorylation of a protein is determined by the relative activity of Ser/Thr-specific protein kinase and protein phosphatase. It is therefore imderstandable that the cell has had to develop special mechanisms to balance the two activities with one another, and, when needed, to allow kinase or phosphatase activity to dominate. One of the best investigated examples of coordinated activity of protein kinases and protein phosphatases is the regulation of glycogen metabolism in skeletal muscle. Glycogen metabolism is an example of how two different signals, namely a cAMP signal and a Ca signal meet in one metabolic pathway and control the activity of one and the same enzyme. 

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