Regulatory enzymes sequences

The receptor protein (52 kDa) is a member of the steroid hormone receptor superfamily, which has a DNA-binding as well as ligand-binding domain. Another receptor, the retinoid X receptor is also involved, and after binding of the peroxisome proliferator, the two receptors form a heterodimer. This binds to a regulatory DNA sequence known as the peroxisome proliferator response element. The end result of the interaction between peroxisome proliferators and this system is that genes are switched on, leading to increases in synthesis (induction) of both microsomal and peroxisomal enzymes and possibly hyperplasia. 

Most of the enzymes in each metabolic pathway follow the kinetic patterns we have already described. Each pathway however, includes one or more enzymes that have a greater effect on the rate of the overall sequence. These regulatory enzymes exhibit increased or decreased catalytic activity in response to certain signals. Adjustments in the rate of reactions catalyzed by regulatory enzymes, and therefore in the rate of entire metabolic sequences, allow the cell to meet changing needs for energy and for biomolecules required in growth and repair. 

In most multienzyme systems, the first enzyme of the sequence is a regulatory enzyme. This is an excellent place to regulate a pathway, because catalysis of even the first few reactions of a sequence that leads to an unneeded product diverts energy and metabolites from more important processes. Other enzymes in the sequence are usually present at levels that provide an excess of catalytic activity they can generally promote... 

The amino acid biosynthetic pathways are subject to allosteric end-product inhibition the regulatory enzyme is usually the first in the sequence. Regulation of the various synthetic pathways is coordinated. 

The concept of control of metabolic activity by allosteric enzymes or the control of enzyme activity by ligand-induced conformational changes arose from the study of metabolic pathways and their regulatory enzymes. A good example is the multi-enzymatic sequence catalysing the conversion of L-threonine to L-isoleucine shown in Fig. 5.32. 

Metabolic sequences occur in oppositely directed pairs, which are controlled by regulatory enzymes. 

The sequences of biochemical transformations involved in the synthesis of the aspartate family and branched-chain amino acids in multicellular plants are similar to those that occur in microorganisms. Support for this conclusion has been derived principally from isolation of a number of the requisite enzymes. Information on the kinetic and physical properties of enzymes is best achieved after extensive purification. In contrast, useful predictions of the physiological function of regulatory enzymes depend upon effective enzyme extraction and complete preservation of native properties. Since the latter objective has been emphasized during most investigations of enzymes associated with amino acid biosynthesis in plants, the bulk of our knowledge has been obtained from comparatively crude enzyme preparations. Results of both direct and competitive labeling experiments have added demonstrations of many of the predicted precursor-product relationships and a few metabolic intermediates have been isolated from plants. The nature of a number of intermediate reactions does, however, remain to be clarified notably, the reactions associated with the conversion of dihydropicolinate to lysine and those involved in the synthesis of leucine from 2-oxoisovalerate. 

Fig. 2. Generalized interaction between adenylate energy charge and the concentration of a metabolite modifier expected in the control of a regulatory enzyme in an amphibolic sequence. The curves correspond to low (/), normal ( ), and high h) concentrations of the metabolite modifier, From Atkinson [9],...

Many regulatory enzymes are allosterically controlled by a product or products of the reaction sequence that is to say they are subject to feedback control. The binding of an effector to the enzyme causes a conformational change which is transmitted to the active site and causes either an increase or a decrease in activity over a range of substrate concentrations. Frequently, in the absence of an activator or in the presence of an inhibitor, the enzyme exhibits sigmoidal kinetics with respect to substrate concentration. Addition of the activator or removal of the inhibitor restores normal saturation kinetics. 

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