Metabolic reactions control

As indicated in the previous discussion, the control of enzyme activity is understood in terms of kinetic parameters. Differences in Km and or Vmax can also arise when the same chemical (metabolic) reaction is catalysed by two structurally different enzymes. Such is the case with isoenzymes or isoforms of enzymes. 

Q <23 From experience, you know that you produce significantly more heat when you are exercising than when you are resting. Scientists can study the heat that is produced by human metabolism reactions using a human calorimeter. Based on what you know about calorimetry, how would you design a human calorimeter What variables would you control and study in an investigation using your calorimeter ... 

Selective labelling of the two diastereotopic methyl groups of i-leucine (144) has enabled their fates during secondary metabolic reactions to be elucidated [66]. Moreover, in the context of protein interactions, differentiation of the leucine pro-R and pro-S methyl groups in protein NMR spectra allows molecular recognition phenomena to be studied [67]. Recently, efficient routes to both forms of Relabeled leucine, based on application of an auxiliary-controlled stereoselective conjugate addition reaction (Scheme 6.27) have been described [68]. Thus, starting... 

Typically, a specific enzyme catalyzes each chemical reaction in the metabolism of an organism. This specificity is required to properly regulate metabolism. One needs to be able to independently control the rates of aU, or almost all, metabolic reactions, enzyme by enzyme. 

Although details will vary, in each case an agonist at its receptor activates adenylate cyclase and the second messenger cAMP is produced from ATP. cAMP activates protein kinase A and a cascade of reactions may follow. These may be metabolic reactions, as in the cases just described, or activation of a cAMP response-element protein, CREB. CREB is a transcription factor with affinity for specific sites on DNA. Control of protein synthesis follows. 

Anaerobic metabolism occnrs nnder conditions in which the diffusion rate is insufficient to meet the microbial demand, and alternative electron acceptors are needed. The type of anaerobic microbial reaction controls the redox potential (Eh), the denitrification process, reduction of Mu and SO , and the transformation of selenium and arsenate. Keeney (1983) emphasized that denitrification is the most significant anaerobic reaction occurring in the subsurface. Denitrification may be defined as the process in which N-oxides serve as terminal electron acceptors for respiratory electron transport (Firestone 1982), because nitrification and NOj" reduction to produce gaseous N-oxides. hi this case, a reduced electron-donating substrate enhances the formation of more N-oxides through numerous elechocarriers. Anaerobic conditions also lead to the transformation of organic toxic compounds (e.g., DDT) in many cases, these transformations are more rapid than under aerobic conditions. 

In the cell, the free Ca concentration is subject to strict regulation, and targeted increase of Ca concentration is a universal means of controlling metabolic reactions. Several processes are involved in its regulation (Fig. 6.6) release from Ca storage, Ca influx from the extracellular space and transport back into the Ca storage. 

Kamo et al. [Biochim. Biophys. Acta, 367, 1 and 11 (1974)] have shown that nonionic sugars modify the zeta potential of slime mold cells. Aggregation of colloids is related to their surface charge and their surface potential. This fact shows evidence of long-range electrostatic interactions controlled by metabolic reactions taking place at the membrane and able to modify the composition of the membrane medium interface. In this process the diffusion is not relevant, as indicated by Mrs. Babloyantz. 

Figure 11-1 Some control elements for metabolic reactions. Throughout the book modulation of the activity of an enzyme by allosteric effectors or of transcription and translation of genes is indicated by dotted lines from the appropriate metabolite. The lines terminate in a minus sign for inhibition or repression and in a plus sign for activation or derepression. Circles indicate direct effects on enzymes, while boxes indicate repression or induction of enzyme synthesis.

The control of glycogen phosphorylase by the phosphorylation-dephosphorylation cycle was discovered in 1955 by Edmond Fischer and Edwin Krebs50 and was at first regarded as peculiar to glycogen breakdown. However, it is now abundantly clear that similar reactions control most aspects of metabolism.51 Phosphorylation of proteins is involved in control of carbohydrate, lipid, and amino acid metabolism in control of muscular contraction, regulation of photosynthesis in plants,52 transcription of genes,51 protein syntheses,53 and cell division and in mediating most effects of hormones. 

Control elements of metabolic reactions 536 Controllability coefficient 537 Coomassie brilliant blue 102,122s Cooperative binding 352 of protons 331 of substrate 476... 

Other forms of vanadium have been implicated in the stimulation of the plasma membrane vanadate-dependent NAD(P)H oxidation reaction. Decavanadate has been shown to be a more potent stimulator of the vanadate-dependent NADH oxidation activity than added orthovanadate [30,31], Interestingly, decavanadate reductase activity has been found to be an alternative activity of an NADP-specific isocitrate dehydrogenase [32], Diperoxovanadium derivatives have also been shown to be involved in this type of reaction [33,34], Decavanadate may play a role in the biological role of vanadium, as it is found in yeast cells growing in the presence of orthovanadate [8] and is a potent inhibitor of phosphofructokinase-1, the control step of glycolysis, and other metabolic reactions [35],... 

Hundreds of metabolic reactions take place simultaneously in cells. There are branched and parallel pathways, and a single biochemical may participate in severm distinct reactions. Through mass action, concentration changes caused by one reaction may effect the kinetics and equilibrium concentrations of another. In order to prevent accumulation of too much of a biochemical, the product or an intermediate in the pathway may slow the production of an enzyme or may inhibit the activation of enzymes regulating the pathway. This is termed feedback control and is shown in Fig. 24-1. More complicated examples are known where two biochemicals act in concert to inhibit an enzyme. As accumulation of excessive amounts of a certain biochemical may be the key to economic success, creating mutant cultures with defective metabolic controls has great value to the production of a given product. 

Many reactions in metabolism are controlled by the energy status of the cell. One index of the energy status is the energy charge, which is proportional to the mole fraction of ATP plus half the mole fraction of ADP, given that ATP contains two anhydride bonds, whereas ADP contains one. Hence, the energy charge is defined as... 

Although the above equation represents the overall metabolic reaction for carbohydrates, there are actually over thirty individual reactions. Each reaction is controlled by a different enzyme. The failure of an enzyme to function may have serious and possibly fatal consequences. Slightly less than half of the 686 kcal/mole of the energy produced by combustion is available for storage and use by the cell with the remaining amount dissipated as heat... 

How can we define the molecular basis of specific phenotypic states Cells such as muscle or secretory cells must have characteristic patterns of biochemical reactions that support their structural properties and metabolic functions. The persistence of a cell in a steady phenotypic state suggests that the underlying network of metabolic reactions also operates in a steady state. The metabolic network is controlled by signaling molecules that promote or... 

The microspheres (7) which form easily from proteinoids (67 Fig. 14) lend themselves to the investigation of another facet of enzyme chemistry, the study of distribution and coordination of activity in particulate systems. This kind of exploration is particularly needed for enzymes, inasmuch as their organismic setting is in close relationship in a membrane-controlled unit, the cell. The substrates which are acted upon by enzymes are also governed by rates of diffusion. The role of the cell in metabolic reactions must be manifold, and is largely not yet understood. 

Since a variety of en2ymatic reactions control the energy metabolism in parasitic helminths, the following biochemical targets may be utilized for effective design of new anthelmintics. 

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