Primary And Secondary Metabolism

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All organisms need to transform and interconvert a vast number of organic compounds to enable them to live, grow, and reproduce. They need to provide themselves with energy in the form of ATP, and a supply of building blocks to construct their own tissues. An integrated network of enzymemediated and carefully regulated chemical reactions is used for this purpose, collectively referred to as intermediary metabolism, and the pathways involved are termed metabolic pathways. Some of the crucially important molecules of life are carbohydrates, proteins, fats, and nucleic acids. Apart from fats, these are polymeric materials. Carbohydrates are composed of sugar units, whilst proteins are made up from amino acids, and nucleic acids are based on nucleotides. Organisms vary widely in their capacity to synthesize and transform chemicals. For instance, plants are very efficient at synthesizing organic compounds via photosynthesis from inorganic materials found in the environment, whilst other organisms such as animals and microorganisms rely on obtaining their raw materials in their diet, e.g. by consuming plants. Thus, many of the metabolic pathways are concerned with degrading materials taken in as food, whilst others are then required to synthesize specialized molecules from the basic compounds so obtained.

Despite the extremely varied characteristics of living organisms, the pathways for generally modifying and synthesizing carbohydrates, proteins, fats, and nucleic acids are found to be essentially the same in all organisms, apart from minor variations. These processes demonstrate the fundamental unity of all living matter, and are collectively described as primary metabolism, with the compounds involved in the pathways being termed primary metabolites. Thus degradation of carbohydrates and sugars generally proceeds via the well characterized pathways known as glycolysis and the Krebs/citric acid/tricarboxylic acid cycle, which release energy from the organic compounds by oxidative reactions. Oxidation of fatty acids from fats by the sequence called P-oxidation also provides energy. Aerobic organisms are able to optimize these processes by adding on a further process, oxidative phosphorylation. This improves the efficiency of oxidation by incorporating a more general process applicable to the oxidation of a wide variety of substrates rather than having to provide specific processes for each individual substrate. Proteins taken in via the diet provide amino acids, but the proportions of each will almost certainly vary from the organism's requirements. Metabolic pathways are thus available to interconvert amino acids, or degrade those not required and thus provide a further source of energy. Most organisms can synthesize only a proportion of the amino acids they actually require for protein synthesis. Those structures not synthesized, so-called essential amino acids, must be obtained from external sources.

In contrast to these primary metabolic pathways, which synthesize, degrade, and generally inter-convert compounds commonly encountered in all organisms, there also exists an area of metabolism concerned with compounds which have a much more limited distribution in nature. Such compounds, called secondary metabolites, are found in only specific organisms, or groups of organisms, and are an expression of the individuality of species. Secondary metabolites are not necessarily produced under all conditions, and in the vast majority of cases the function of these compounds and their benefit to the organism is not yet known. Some are undoubtedly produced for easily appreciated reasons, e.g. as toxic materials providing defence against predators, as volatile attractants towards the same or other species, or as colouring agents to attract or warn other species, but it is logical to assume that all do play some vital role for the well-being of the producer. It is this area of secondary metabolism that provides most of the pharmacologically active natural products. It is thus fairly obvious that the human diet could be both unpalatable and remarkably dangerous if all plants, animals, and fungi produced the same range of compounds.

The above generalizations distinguishing primary and secondary metabolites unfortunately leave a 'grey area' at the boundary, so that some groups of natural products could be assigned to either division. Fatty acids and sugars provide good examples, in that most are best described as primary metabolites, whilst some representatives are extremely rare and found only in a handful of species. Likewise, steroid biosynthesis produces a range of widely distributed fundamental structures, yet some steroids, many of them with pronounced pharmacological activity, are restricted to certain organisms. Hopefully, the blurring of the boundaries will not cause confusion; the subdivision into primary metabolism (= biochemistry) or secondary metabolism (= natural products chemistry)

is merely a convenience and there is considerable overlap.

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