The Central Role of ATP in Metabolism

Where possible we have used the free energies AG calculated from in vivo concentrations of metabolites rather than the standard free energies AG, which do not take account of local concentrations of reactants and products. 

FIGURE 5.5 The coupled reaction in which ATP supplies the phosphoryl group for glucose-6-phosphate synthesis in contrast, phospho-enolpyruvate has a phosphoryl transfer potential sufficiently elevated to enable it to donate its phosphoryl group to ADP, generating ATP. 

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The ways in which energy in the form of ATP is produced and utilized constitute bioenergetics, and will be discussed in greater detail at the end of this chapter. However, before turning to a selection of metabolic pathways, we outline some fundamental notions concerning redox reactions followed by a brief description of the central role of ATP in metabolism as an acceptor and donor of phosphoryl groups, and finally a summary of the types of reactions that we will encounter as we wend our way along a sample of some of the pathways of intermediary metabolism. 

The first metabolic pathway elucidated was the glycolytic pathway during the first half of the 20 century by Embden and Meyerhof. Otto Warburg, Cori and Parnas also made very important contributions relating to glycolytic pathway. Krebs established the citric acid and urea cycles during 1930-40. In 1940, Lipmarm described the central role of ATP in biological systems. 

ADP) and inorganic phosphate (Pi) is a strongly endergonic reaction that is coupled to exergonic reactions such as the breakdown of glucose. ATP hydrolysis in turn powers many of life s processes. The central role of ATP in bioenergetics is illustrated in Fig. 1. Partial structures of several compounds that play important roles in metabolism are shown in Fig. 2. 

Riboflavin, also known as vitamin B2, is the central component of FAD and FMN, and is therefore required by all flavo proteins. It plays an important role in the metabolism of fats, ketone bodies, carbohydrates, and proteins. Riboflavin for industrial use is mainly produced from ascomycete fungi in aerobic fermentation. Three quarters of riboflavin is used as a feed additive and the remaining is used as food additives and in pharmaceuticals. Furthermore, FMN can be synthesized by chemical phosphorylation from riboflavin, while FAD can be produced by chemical synthesis or by microbial transformation, which uses FMN and ATP as the substrates. ... 

The reversibility of the metaboUc reaction chains, the crossing over of intermediates and the role of ATP as central store of activating energy and as a factor in regulation of metabolic rates by synchronization of the rate of ATPase activities with those of certain... 

Purines such as ATP and adenosine play a central role in the energy metabolism of all life forms. This fact probably delayed recognition of other roles for purines as autocrine and paracrine substances and neurotransmitters. Today it is recognized that purines are released from neurons and other cells and that they produce widespread effects on multiple organ systems by binding to purinergic receptors located on the cell surface. The principal ligands for... 

Mitochondria play a central role in a variety of biological processes, including ATP synthesis, steroid hormone synthesis, the urea cycle, lipid and amino acid metabolism, and cellular Ca2+ homeostasis. Ca2+ is an essential regulator of vital processes, such as secretion, motility, metabolic control, synaptic plasticity, proliferation, gene expression and apoptosis. Therefore, the location, amplitude,... 

Nucleotides play central roles in metabolism. They serve as sources of chemical energy (ATP and guanosine triphosphate (GTP)), participate in cellular signalling (cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP)) and are incorporated into important cofactors of enzymatic reactions. Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA (Scheme 3). 

Pantothenic acid has a central role in energy-yielding metabolism as the functional moiety of coenzyme A (CoA), in the biosynthesis of fatty acids as the prosthetic group of acyl carrier protein, and through its role in CoA in the mitochondrial elongation of fatty acids the biosynthesis of steroids, porphyrins, and acetylcholine and other acyl transfer reactions, including postsynthetic acylation of proteins. Perhaps 4% of all known enzymes utilize CoA derivatives. CoA is also bound by disulfide links to protein cysteine residues in sporulating bacteria, where it may be involved with heat resistance of the spores, and in mitochondrial proteins, where it seems to be involved in the assembly of active cytochrome c oxidase and ATP synthetase complexes. 

ATP plays a central role in cellular maintenance both as a chemical for biosynthesis of macromolecules and as the major soirrce of energy for all cellular metabolism. ATP is utilized in numerous biochemical reactions including the eitric acid cycle, fatty acid oxidation, gluconeogenesis, glycolysis, and pyruvate dehydrogenase. ATP also drives ion transporters sueh as Ca -ATPase in the endoplasmic reticulum and plasma membranes, H+-ATPase in the lysosomal membrane, and Na+/K+-ATPase in the plasma membrane. Chemieal energy (30.5 kJ/mol) is released by the hydrolysis of ATP to adenosine diphosphate (ADP). 

In the second stage, these numerous small molecules are degraded to a few simple units that play a central role in metabolism. In fact, most of them—sugars, fatty acids, glycerol, and several amino acids—are converted into the acetyl unit of acetyl CoA (Section 14.3.1). Some ATP is generated in this stage, but the amount is small compared with that obtained in the third stage. 

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