Tricarboxylic acid cycle regulation

Coenzyme availability can also often have a limiting effect (5). If the coenzyme is regenerated by a second, independent metabolic pathway, the speed of the second pathway can limit that of the first one. For example, glycolysis and the tricarboxylic acid cycle are mainly regulated by the availability of NAD" (see p. 146). Since NAD is regenerated by the respiratory chain, the latter indirectly controls the breakdown of glucose and fatty acids (respiratory control, see p. 144). 

The most important regulator of p-oxida-tion is the NAD /NADH+H ratio. If the respiratory chain is not using any NADH+H, then not only the tricarboxylic acid cycle (see p. 136) but also p-oxidation come to a standstill due to the lack of NADT... 

How could the activities of the kinase and phosphorylase be regulated so as to control the entry of pyruvate into the tricarboxylic acid cycle ... 

B. S. Sacktor and E. Wormser-Shavit, Regulation of metabolism in working muscle in vivo. I. Concentrations of some glycolytic, tricarboxylic acid cycle, and amino acid intermediates in insect flight muscle during flight, J. Biol. Chem., 241 (1966) 624-631. 

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). 

Buchanan, R. L. and Lewis, D. F. 1984. Regulation of aflatoxin biosynthesis Effect of glucose on the activities of various glycolytic enzymes. Appl. Environ. Microbiol. 48, 306-310. Buchanan, R. L., Federowicz, D., and Stahl, H. G. 1985. Activities of tricarboxylic acid cycle... 

Despite the thousands of secondary metabolites made by microorganisms, they are synthesized from only a few key precursors in pathways that comprise a relatively small number of reactions and which branch off from primary metabolism at a limited number of points. Acetyl-CoA and propionyl-CoA are the most important precursors in secondary metabolism, leading to polyketides, terpenes, steroids, and metabolites derived from fatty acids. Other secondary metabolites are derived from intermediates of the shikimic acid pathway, the tricarboxylic acid cycle, and from amino acids. The regulation of the biosynthesis of secondary metabolites is similar to that of the primary processes, involving induction, feedback regulation, and catabolite repression [6]. 

In class VI are ADP-Glc PPases from anaerobic bacteria Rhodospirillum, capable of growing in either hetero-trophic conditions in the dark or autotrophic conditions in the light under anoxygenic photosynthesis (Table 1). These organisms cannot catabolize glucose but grow very well on pyruvate and tricarboxylic acid cycle (TCA) intermediates. ADP-Glc PPases from class VI are specifically regulated by pyruvate (Table... 

NAD levels regulate an array of vital cellular processes. NAD serves as a cofaCTor for glycolysis and the tricarboxylic acid cycle, thus providing ATP for most cellular processes. 

Fig. 3 Model for regulation of mcl-PHA at the enzymatic ievel in P. putida GPol. Alkanoic acids of mcl (C -Cj ) are taken up by the cell and enter the P-oxidation cycle. The mcl-PHA synthase preferentially polymerizes only (/f)-3-hydroxyacyl-CoA of mcl. It is proposed that during accumulation degradation tilso teikes place (Ren et al. 2009 Tinn 1998). Depending on the energetic status of the cell, the 3-hydroxytilktmoate can be excreted or recycled to (/J)-3-hydroxyacyl-CoA by the acyl-CoA synthetase. Consequently, (R)-3-hydroxyacyl-CoA can be polymerized to mcl-PHA again or channeled back to the p-oxidation cycle and subsequently to the tricarboxylic acid cycle for energy gtiin...

The need for energy by the cell regulates the tricarboxylic acid cycle, which acts in concert with the electron transfer chain and the ATPase to produce adenosine triphosphate in the inner mitochondrial membrane. The cell has limited amounts of ATP, adenosine diphosphate (ADP), and adenosine monophosphate (AMP). When ADP levels are higher than ATP, the cell needs energy, and hence NADH is oxidized rapidly and the tricarboxylic acid cycle is accelerated. When the ATP level is higher than ADP, the cell has the energy needed hence, the electron transport chain slows down. 

Fig. 39.2 Suggested effects leading to neuroprotective activity of hupA in AD. HupA is considered to modulate the APP processing by inducing the activity of a-secretase. The increased activity of a-secretase causes enhancement of nutritional APP (sAPPa) and consequently inhibition the A[i pathway. These APP-modulating effects are mediated through Ml muscarinic receptor-mediated PKC-dependent cascade and Trk receptor-mediated ERK/MAPK-dependent cascade and caused by increased levels of ACh and NGF in the synaptic junction. Increased release of sAPPa and decreased A(3 release from APP followed by inhibition of A[i fibril formations affects the regulation of the expression of apoptotic proteins, attenuates oxidative stress, and allows the mitochondria, respiratory chain, and TCA cycle to function normally. APP amyloid precursor protein, PKC protein kinase C. ERK extracellular signal-regulating kinase, MAPK mitogen-activated protein kinase, TCA tricarboxylic acid cycle (citric acid cycle)...

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