Metabolic regulation enzyme concentration

Aiming at a computer-based description of cellular metabolism, we briefly summarize some characteristic rate equations associated with competitive and allosteric regulation. Starting with irreversible Michaelis Menten kinetics, the most common types of feedback inhibition are depicted in Fig. 9. Allowing all possible associations between the enzyme and the inhibitor shown in Fig. 9, the total enzyme concentration Er can be expressed as... 

A principle in metabolic regulation that allows one to identify the inhibited step within a metabolic pathway as that reaction for which the concentrations of reactants and products rise and fall, respectively, from their steady-state values when an inhibitor is introduced. In the context of the electron transfer chain, the crossover-point refers to that reaction step demarking the transition from more reduced to more oxidized respiratory enzymes. 

Some enzymes and carriers are synthesized only in response to the presence of the sugar, or of a structurally similar compound these enzymes and carriers are said to be inducible. Contrariwise, enzyme synthesis may be repressed by an increase in the concentration of ATP, or of some other metabolite. Induction and repression of enzymes and carriers provide two important kinds of control in metabolic regulation. 

Inhibition of the initial step of a biosynthetic pathway by an end product of the pathway is a recurrent theme in metabolic regulation. In addition, many key enzymes are regulated by ATP, adenosine diphosphate (ADP), AMP, or inorganic phosphate ion (Pi). The concentrations of these materials provide a cell with an index of whether energy is abundant or in short supply. Because ATP, ADP, AMP, or P often are chemically unrelated to the substrate of the enzyme that must be regulated, they usually bind to an allosteric site rather than to the active site. 

FABPs have been implicated in transmembrane and intracellular transport of fatty acids (Veerkamp et al., 1991 Storch and Thumser, 2000). These are a group of tissue-specific proteins of about 14-15 kDa that bind long-chain fatty acids (C16-C20) with high affinity and a molar stoichiometry of 1 1. Most bind unsaturated fatty acids with higher affinity than saturated fatty acids. In addition to transport functions it has been proposed that they modulate specific enzymes of lipid metabolism, regulate expression of fatty acid-responsive genes, maintain cellular membrane fatty acid levels, and reduce the concentration of fatty acids in the cell, thereby removing their inhibitory effect on metabolic processes. 

ATCase and many (but not all) enzymes subject to metabolic regulation have a second interesting property their reaction velocity is not a hyperbolic function of substrate (aspartate) concentration, as... 

In addition to regulating the direction of metabolic pathways, cells, especially those in multicellular organisms, also exert control at three different levels allosteric enzymes, hormones, and enzyme concentration. 

Nearly all of these chemical transformations are catalyzed en-zymically within the plasmalemma (inside the yeast cell-wall), which is the semipermeable membrane that encloses the protoplasm. Many of these enzymes are present in the cells, even under widely differing conditions of their growth, but a number of processes are involved in enzymic regulation and, thus, in the regulation of sugar catabolism. Some enzymes may be synthesized only in response to the presence of the sugar or of a structurally similar compound. Contrariwise, enzyme synthesis may be repressed by an increase in the concentration of ATP or of some other end-product. These enzyme inductions (for a review, see Ref. 5) and repressions (for a review, see Ref. 6) are two important kinds of control in metabolic regulation. 

To obtain citric acid as the metabolic product again requires interference with the normal Krebs tricarboxylic acid cycle in such a way that citric acid metabolism is blocked. Usually this is achieved by careful regulation of concentrations of trace metals available as coenzymes to the various enzyme pathways used by A. niger, so that some of these are rendered ineffective (are blocked). 

Aside from the inordinately dominant light of molecular genetics, the new wave in biochemistry today is, what has come to be called, metabolic control analysis (MCA) (Comish-Bowden and Cardenas, 1990). The impetus behind this wave is the desire to achieve a holistic view of the control of metabolic systems, with emphasis on the notion of system. The classical, singular focus on individual, feedback-modulated (e.g., allosteric), rate-limiting enzymes entails a naive and myopic view of metabolic regulation. It has become increasingly evident that control of metabolic pathways is distributive, rather than localized to one reaction. MCA places a given enzyme reaction into the kinetic context of the network of substrate-product connections, effector relationships, etc., as supposedly exist in situ, it shows that control of fluxes, metabolite concentrations, inter alia, is a systemic function and not an inherent property of individual enzymes. Such... 

The role of the APS sulfohydrolases in sulfate metabolism is not understood precisely. The lysosomal APS sulfohydrolase can hydrolyze bis(4-nitro-phenyl) phosphate and 4-nitrophenyl 5 -phosphothymidine (Roger et al., 1978). Thus the lysosomal APS sulfohydrolase is less specific than its cytosolic counterpart, which does not hydrolyze these nitrophenyl derivatives. The apparent role of the lysosomal enzyme is to hydrolyze the acid anhydrides of such compounds as FAD, ATP, and ADP in secondary lysosomes. Thus lysosomal APS sulfohydrolase is an acid anhydride hydrolase that helps the cell in the recovery of nucleoside monophosphates from acid anhydrides. The APS sulfohydrolase in the cytosolic fraction probably regulates the concentrations of PAPS and therefore plays an important role in the control of sulfate conjugation. 

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