Metabolic pathways regulation

Understand enzyme regulation via cellular enzyme levels, compartmentation, metabolic pathway regulation, and covalent modifications. 

FIGURE 11.6 Metabolic pathways regulating organic matter decomposition and nntrient release. 

Natural or induced mutations can prove to be very powerful tools to use for the study of metabolic pathway regulation. Biosynthetic perturbations resulting from alterations to structural and/or regulatory genes have already been observed in tomato and the iirforma-tion gathered from these systems has already proved very valuable. 

Quo, C.F., Moffitt, R.A., MerriU, A.H., Wang, M.D. (2011) Adaptive control model reveals systematic feedback and key molecules in metabolic pathway regulation. J Comput. Biol. 18, 169-182. 

Allosteric regulation acts to modulate enzymes situated at key steps in metabolic pathways. Consider as an illustration the following pathway, where A is the precursor for formation of an end product, F, in a sequence of five enzyme-catalyzed reactions ... 

Interestingly, anabolism and catabolism occur simultaneously in the cell. The conflicting demands of concomitant catabolism and anabolism are managed by cells in two ways. First, the cell maintains tight and separate regulation of both catabolism and anabolism, so that metabolic needs are served in an immediate and orderly fashion. Second, competing metabolic pathways are often... 

Citrate synthase is the first step in this metabolic pathway, and as stated the reaction has a large negative AG°. As might be expected, it is a highly regulated enzyme. NADH, a product of the TCA cycle, is an allosteric inhibitor of citrate synthase, as is succinyl-CoA, the product of the fifth step in the cycle (and an acetyl-CoA analog). 

The photosynthetic COg fixation pathway is regulated in response to specific effects induced in chloroplasts by light. What is the nature of these effects, and how do they regulate this metabolic pathway ... 

Several of the problems associated with whole cell bioprocesses are related to the highly effective metabolic control of microbial cells. Because cells are so well regulated, substrate or product inhibition often limits the concentration of desired product that can be achieved. This problem is often difficult to solve because of a poor understanding of the kinetic characteristics of the metabolic pathway leading to the desired product. 

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. 

Controlling an Enzyme That Catalyzes a Rate-Limiting Reaction Regulates an Entire Metabolic Pathway... 

THE FLUX OF METABOLITES IN METABOLIC PATHWAYS MUST BE REGULATED IN A CONCERTED MANNER... 

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. 

As the RPE plays an important role in lipid metabolism and regulation of dynamic transport between the choriocapillaris and photoreceptors, it is important to determine whether carotenoids affect these pathways in the RPE. 

Webb GC et al. Expression profiling of pancreatic (S cells glucose regulation of secretory and metabolic pathway genes. Proc Natl Acad Sci USA 2000 97 5773-5778. 

Brown MS, Goldstein JL. The SREBP pathway regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell 1997 89 331-340. 

Information metabolism provides a way to store and retrieve the information that guides the development of cellular structure, communication, and regulation. Like other metabolic pathways, this process is highly regulated. Information is stored by the process of DNA replication and meiosis, in which we form our germ-line cells. These processes are limited to specific portions of the cell cycle. Information is retrieved by the transcription of DNA into RNA and the ultimate translation of the signals in the mRNA into protein. 

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