Central metabolism

Although most cells have the same basic set of central metabolic pathways, different cells (and, by extension, different organisms) are characterized by the alternative pathways they might express. These pathways offer a wide diversity... 

A variety of starting materials other than glucose or its derivatives is possible for use by some micro-organisms the four shown in Figure 5.1 are all initially converted to acetyl CoA for entry into the central metabolic pathways. 

In Table 9-5 we have listed a large number of reaction types. For many of these reaction types you may be able to think of examples from central metabolism. For example, the oxidation of alcohols to ketones is a very commonly encountered reaction. Thus ... 

Similarly, the introduction of double bonds, isomerisation or hydrolysis are also frequently encountered reactions in central metabolism. Many of these reactions have their analogues in sterol/steroid interconversions. Below we will confine ourselves to a limited number of examples. 

The degradation of 2,2 -dihydroxy- 3,3 -dimethoxybiphenyl-5,5 -dicarboxylate (5,5 -dehydro-divanillate) by Sphingomonas paucimobilis SYK-6 proceeds by partial de-O-methylation followed by extradiol hssion of the catechol to 2-hydroxy-3-methoxy-5-carboxybenzoate. Diversion of this into central metabolic pathways involves decarboxylation to vanillate by two separate decarboxylases LigWl and LigW2 (Peng et al. 2005). 

Experimental studies of Methanosarcina and current understanding of the organism s metabolic pathway allow us to estimate the parameters in the thermodynamic term (Qusheng Jin, personal communication). The methanogens conserve about 24 kJ (mol acetate)-1, so we set AGp to 48 kJ mol-1 and m to one half. A double proton translocation occurs within the central metabolic pathway, furthermore, so, if we take these as the rate limiting steps, the average stoichiometric number / is two. 

Nevertheless, using GC-based technologies, the quantification of several important intermediates of central metabolism, especially phosphorylated intermediates, is not very reliable, presumably because these compounds and their derivatives are not thermostable. For an analysis of these groups of metabolites, an LC-MS (liquid chromatography or HPLC coupled to MS) is more suitable, because it eliminates the need for volatility and thermostability and thereby eliminates the need for derivatization. Using a triple quadrupole MS, most of the intermediates in glycolysis, in the pentose phosphate pathway, and in the tricarboxylic acid cycle were measured in E. coli [214]. 

Besides the two most well-known cases, the local bifurcations of the saddle-node and Hopf type, biochemical systems may show a variety of transitions between qualitatively different dynamic behavior [13, 17, 293, 294, 297 301]. Transitions between different regimes, induced by variation of kinetic parameters, are usually depicted in a bifurcation diagram. Within the chemical literature, a substantial number of articles seek to identify the possible bifurcation of a chemical system. Two prominent frameworks are Chemical Reaction Network Theory (CRNT), developed mainly by M. Feinberg [79, 80], and Stoichiometric Network Analysis (SNA), developed by B. L. Clarke [81 83]. An analysis of the (local) bifurcations of metabolic networks, as determinants of the dynamic behavior of metabolic states, constitutes the main topic of Section VIII. In addition to the scenarios discussed above, more complicated quasiperiodic or chaotic dynamics is sometimes reported for models of metabolic pathways [302 304]. However, apart from few special cases, the possible relevance of such complicated dynamics is, at best, unclear. Quite on the contrary, at least for central metabolism, we observe a striking absence of complicated dynamic phenomena. To what extent this might be an inherent feature of (bio)chemical systems, or brought about by evolutionary adaption, will be briefly discussed in Section IX. 

S. Klamt, S. Schuster, and E. D. Gilles, Calculability analysis in underdetermined metabolic networks illustrated by a model of the central metabolism in purple nonsulfur bacteria. Biotechnol. Bioeng. 77(7), 734 751 (2002). 

Tang YJ, Ashcroft JM, Chen D, Min G, Kim CF1, Murkhejee B, Larabell C, Keasling JD, Chen FF (2007) Charge-associated effects of fullerene derivatives on microbial structural integrity and central metabolism. Nano Lett. 7 754-760. 

One of the great unifying features of life is the similarity in metabolic patterns. As diverse as life forms are, their patterns of metabolic activity— how molecules are formed and degraded—are remarkably closely related. That is not to say that they are identical. They are not. Indeed, identity in metabolic pattern would imply identity in structure and physiology, which is certainly not the case. Nonetheless, the similarities are striking. Variations on a unified central metabolic theme give rise to the diversity of life forms. Nowhere is this fundamental fact more clearly evident than in the central metabolic pathway known as the citric acid cycle. 

Citric acid cycie a central metabolic pathway responsible for converting acetate to carbon dioxide and water with the generation of chemical energy. 

The next part presents the reactions involved in the interconversion of these compounds—the part of biochemistry that is commonly referred to as metabolism (pp. 88-195). The section starts with a discussion of the enzymes and coenzymes, and discusses the mechanisms of metabolic regulation and the so-called energy metabolism. After this, the central metabolic pathways are presented, once again arranged according to the class of metabolite (pp. 150-195). 

A number of central metabolic pathways are common to most cells and organisms. These pathways, which serve for synthesis, degradation, and interconversion of important metabolites, and also for energy conservation, are referred to as the intermediary metabolism. 

Using this approach, general guidelines for experimental design of C-tracer studies with MS could be shown for the central metabolism of Corynebacterium glutamicum comprising various flux scenarios and tracer substrates [26]. 

Bremner JD, Innis RB, Ng CK, Staib L, Duncan J, Bronen R, Zubal G, Rich D, Krystal JH, Dey H, Soufer R, Charney DS (1997b) PET measm-ement of central metabolic correlates of yohimbine administration in posttraumatic stress disorder. Arch Gen Psychiatry 54 246-256... 

The membrane-associated Akt kinase is now a substrate for protein kinase PDKl that phosphorylates a specific Thr and Ser residue of Akt kinase. The double phosphorylation converts Akt kinase to the active form. It is assumed that the Akt kinase now dissociates from the membrane and phosphorylates cytosolic substrates such as glycogen synthase kinase, 6-phosphofructo-2-kinase and ribosomal protein S6 kinase, p70 . According to this mechanism, Akt kinase regulates central metabolic pathways of the cell. Furthermore, it has a promoting influence on cell division and an inhibitory influence on programmed cell death, apoptosis. A role in apoptosis is suggested by the observation that a component of the apoptotic program. Bad protein (see Chapter 15) has been identified as a substrate of Akt kinase. 

A nearly universal set of several hundred small molecules is found in living cells the interconversions of these molecules in the central metabolic pathways have been conserved in evolution. 

The reaction involves biotin as a carrier of activated HCO3 (Fig. 14-18). The reaction mechanism is shown in Figure 16-16. Pyruvate carboxylase is the first regulatory enzyme in the gluconeogenic pathway, requiring acetyl-CoA as a positive effector. (Acetyl-CoA is produced by fatty acid oxidation (Chapter 17), and its accumulation signals the availability of fatty acids as fuel.) As we shall see in Chapter 16 (see Fig. 16-15), the pyruvate carboxylase reaction can replenish intermediates in another central metabolic pathway, the citric acid cycle. 

Holms, W.H. (1986) The central metabolic pathways of Escherichia coli relationship between flux and control at a branch point, efficiency of conversion to biomass, and excretion of acetate. Curr. Top. Cell. Regul 28, 69-106. 

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