Metabolism themes

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. 

Metabolic themes It is difficult to classify microbes on the basis of their metabolic properties, for similar metabolic pathways seem to have been used several times during the development of... 

Ornston LN, W-K Yeh (1982) Recurring themes and repeated sequences in metabolic evolution. In Biodegradation and Detoxification of Environmental Pollutants (Ed AM Chakrabarty), pp. 105-126. CRC Press Inc, Boca Raton. 

Energy metabolism makes sense if you realize that each individual pathway and each organ has a function. Understanding metabolism in every detail may well be impossible, but understanding the general themes is not only possible but important. 

Biochemical studies follow several themes. For example, investigations can be focussed on the chemical structures of molecules, (for example the structure of glycogen, DNA or protein conformation) or the structural inter-relationship between molecules (e.g. enzymes with their substrates, hormones with their receptors). The other branch of biochemical enquiry is into those numerous dynamic events known collectively as metabolism , defined here as all of the chemical reactions and their associated energy changes occurring within cells . The purpose of metabolism is to provide the... 

Life is unified by the molecules of life and by the roles of cells. There are two additional, intimately connected unifying themes energy and the metabolism of the element carbon. Here are the essentials. 

In the preceding chapter, I emphasized the importance of carbohydrates as sources of metabolic energy. I also introduced the idea of metabolic pathways. Now it is time to pull those two themes together and understand how the pathways for metabolism of carbohydrates yield useful metabolic energy and how these processes are controlled. On the way, we will learn how a number of important drugs for human medicine work their therapeutic magic. 

Tkacz JS, Polyketide and peptide products of endophytic fungi Variations on two biosynthetic themes of secondary metabolism, in Bacon CW, White JF, Jr (eds.), Microbial Endophytes Marcel Dekker, Inc., New York, NY, pp. 263—294, 2000. 

Covalent interconversion of enzymes is well established as a fundamental theme in metabolic regulation. The prototypic reversible interconverting systems include the sequence of phosphorylation/dephosphorylation steps in the activation of mammalian glycogen phosphorylase and pyruvate dehydrogenase as well as the nucleotidyla-tion/denucleotidylation using UTP and ATP in the bacterial glutamine synthetase cascade (see Fig. 1.). 

This diversity of mental retardation, in both cause and phenotype, carries important implications for consideration of the biochemistry of consciousness. On the one hand, because this is an investigation of multiple causalities—including, for example, inborn errors of metabolism, each of which has its own unique biochemical profile (Cook Leventhal, 1996), it may not prove possible to identify specific neurotransmitter abnormalities which are common to mental retardation as such. On the other hand common themes concerning key neurotransmitters may be identified from studies of mental retardation. Altered neurotransmitter functioning associated with the severity of mental retardation is open to different interpretations, either reflecting fundamentally impaired development of cerebral structure or a more general impairment of central transmitter activity and functioning. 

The inverse technique, which makes use of complexation of compounds to the product such that it becomes insoluble (e.g. fatty acids with barium cations), is also applied. These methods are also applicable for strains that do not grow on the screening compound due to lack of a complete metabolic pathway for the starting material. A variation on this theme is the trapping of radioactive tracers, such as... 

Metabolic regulation, a central theme in biochemistry, is one of the most remarkable features of a living cell. Of the thousands of enzyme-catalyzed reactions that can take place in a cell, there is probably not one that escapes some form of regulation. Although it... 

Two other features deserve mention. First, there is evidence, especially in the de novo purine pathway, that the enzymes are present as large, multienzyme complexes in the cell, a recurring theme in our discussion of metabolism. Second, the cellular pools of nucleotides (other than ATP) are quite small, perhaps 1% or less of the amounts required to synthesize the cell s DNA. Therefore, cells must continue to synthesize nucleotides during nucleic acid synthesis, and in some cases nucleotide synthesis may limit the rates of DNA replication and transcription. Because of the importance of these processes in dividing cells, agents that inhibit nucleotide synthesis have become particularly important to modern medicine. 

Each one of the thousands of chemical reactions of metabolism is catalyzed by an enzyme. Most of these enzymes are proteins, but others are made from RNA (ribonucleic acid). In both cases enzymes are very large molecules with precise three-dimensional structures. The study of the properties of enzymes and of enzymatic catalysis is a third theme of the book. Not only are the chemical mechanisms by which enzymes act of interest but also enzymes are often targets for useful drugs. Incorrectly formed enzymes can result in serious diseases. 

Inhibition of the initial step of a biosynthetic pathway by an end product of the pathway is a recurrent theme in metabolic regulation. In addition, many key enzymes are regulated by ATP, adenosine diphosphate (ADP), AMP, or inorganic phosphate ion (Pi). The concentrations of these materials provide a cell with an index of whether energy is abundant or in short supply. Because ATP, ADP, AMP, or P often are chemically unrelated to the substrate of the enzyme that must be regulated, they usually bind to an allosteric site rather than to the active site. 

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