Anaplerotic sequences

Anaplerotic Sequences The Need to Replace Cycle Intermediates (Figure 14.18)... 

Finally, what areas remain important for future research Prediction is always a dangerous business but to us the key questions of ammonia assimilation all revolve around carbon metabolism—what are the sources for the carbon skeletons of amino acids that are synthesized in the chloroplast How do the anaplerotic sequences that provide a ready supply of 2-oxoglutarate and oxoloacetate operate and how are they controlled What are the critical steps that ensure, in times of plentiful ammonia supply, that sufficient carbohydrates are transported and oxidised And perhaps most interestingly of all, how are the electrons needed to reduce and assimilate N2 in nodules and NO in roots generated from carbohydrate transported from the shoot ... 

Metabolic cycles and anaplerotic sequences can partiaUy circumvent stoichiometric and kinetic limitations. 

Metabolic cycle a catalytic series of reactions in which the product of one bimolecular reaction is regenerated A-tB->->—>C + A. Thus A acts catalyti-cally, is required only in small amounts, and can be considered as a carrier of B.The catalytic function of A and other members of the M.c. insure economic conversion of B into C. B is the substrate of the M.c. and C is the product. If intermediates are withdrawn from the M.c., e.g. for biosynthesis, the stationary concentrations of the M.c. intermediates must be maintained by synthesis. Replenishment of depleted M.c. intermediates is called anaplerosis. Only one anaplerotic reaction is necessary, since the resulting intermediate is in equilibrium with all other members of the cycle. Anaplerosis may be served by a single reaction, which converts a common metabolite into an intermediate of the M.c. (e.g. pyruvate to oxalo-acetate in the tricarboxylic acid cycle), or it may involve a metabolic sequence of reactions, i. e. an anaplerotic sequence (e.g. the glycerate pathway which provides phosphoenofpyruvate for anaplerosis of the dicarboxylic acid cycle). 

The tricarboxylic acid cycle (TCA cycle, Krebs cycle, citric acid cycle) is the central primary metabolic process in energy regeneration and production of metabolites in all living cells. It is further present in complete TCA cycle with ten participating acids or modified as incomplete TCA cycle, sometimes with shortcuts by anaplerotic sequences. 

The word amphibolic is often applied to those metabolic sequences that are part of a catabolic cycle and at the same time are involved in a biosynthetic (anabolic) pathway. Another term, anaplerotic, is sometimes used to describe pathways for the synthesis of regenerating substrates. This word, which was suggested by H. L. Komberg, comes from a Greek root meaning "filling up."80... 

Although the major route for aspartate degradation involves its conversion to oxaloacetate, carbons from aspartate can form fumarate in the urea cycle (see Chapter 38). This reaction generates cytosolic fumarate, which must be converted to malate (using cytoplasmic fumarase) for transport into the mitochondria for oxidative or anaplerotic purposes. An analogous sequence of reactions occurs in the purine nucleotide cycle. Aspartate reacts with inosine monophosphate (IMP) to... 

Biochemical pathways may be described as catabolic, anabolic (biosynthetic), amphibolic or anaplerotic. The principal function of a catabolic sequence is to degrade (usually by an oxidative process) simple organic molecules derived from the breakdown of polymers (e.g. amino acids from proteins) and retain some of the free energy released in a biologically useful form. Anabolic pathways consume energy and synthesize (usually by a reductive process) the simple molecules which are assembled into proteins, nucleic acids, carbohydrate polymers and lipids. Amphibolic pathways, such as the tricarboxylic acid cycle, have both catabolic and anabolic properties. They are central metabolic pathways which furnish, from catabolic sequences, the intermediates which form the substrates of anabolic processes. The... 

The utilization of acetyl-CoA by the tricarboxylate cycle is dependent upon the availability of an appropriate intramitochondrial concentration of oxaloacetate which is maintained by anaplerotic reactions (Section 12.6). The intracellular concentration of oxaloacetate therefore depends upon the levels of certain glycolytic intermediates. If carbohydrate metabolism is depressed and fatty acid degradation predominant such as during starvation, fasting or diabetes mellitus, acetyl-CoA cannot enter the tricarboxylate cycle and is utilized by a reaction sequence leading to ketone body formation. There are three so-called ketone bodies ... 

The commercial availability of stable isotope ( C, N, H)-labelled compounds and highly accurate mass spectrometers has made it possible to probe the details of metabolic pathways involved in macronutrient catabolism and neogenesis. This paper highlights aspects of animal nutrition and metabolism in which uniformly C-labelled [U- C] substrates and C-massisotopomer distribution approaches have been applied to investigations of amino acid and carbohydrate synthesis and catabolism. We will focus on the application of [U- C] substrates as tracers in chickens, fish, sheep, and cells in culture to quantify rates of macronutrient synthesis, identification of the sources of dietary nutrients that serve as substrates for neogenesis of macronutrients, and investigations of the intercormectivity of the pathways of macronutrient metabolism with those of the Krebs cycle to preserve metabolic flexibility via anaplerotic and cataplerotic sequences. 

Figure 2. Diagram representing anaplerotic (solid lines and shapes) and cataplerotic (dashed lines and shapes) sequences connecting the Krebs cycle to gluconeogenesis, fatty acid metabolism, and dispensible AA synthesis. Some sequences can serve both anaplerotic and cataplerotic roles, thus linked metabolites (bold) can be catabolized or synthesized. a-KG, a-ketoglutarate OAA, oxaloacetate PEP, phosphoenolpyruvate.

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