PRINCIPLES OF METABOLIC CONTROL

Cells and organisms are relatively isolated systems in a quasi-steady state. The functions of living organisms as a whole as well as of their parts are regulated with the objective of attaining maximum survival. Since the living system reacts in space and time, both spatial and temporal regulation may be employed.

Space comes into play mainly in the higher degree of organization of structures; maintenance of structural stability of proteins, association of cooperating enzymes into multienzyme complexes, their localization in definite compartments (mitochondria, endoplasmic reticulum) and specialization of cells and tissues by differentiation processes.

Time is involved in regulation mainly in terms of modification if reaction rates (metabolic, transport, and others). In practice, both dimensions are utilized simultaneously.

Regulatory mechanisms become effective at very different levels of organization but their basis is always molecular. Functions of an organism can be regulated through reactions taking place in cells (metabolic regulation) and at the level of the whole organism (hormonal, nervous controls). Within a cell, metabolic "processes are controlled mainly by regulating the activity of individual enzymes.

Enzymes can be regulated in several ways:

By changing the concentration of substrates or coenzymes (a metabolic signal) that result in changes of enzyme activity, the amount of the enzyme involved remaining constant. Changes in the concentration of a signal compound are mostly achieved through compartmentation, i.e. by forming membranes separating the cell from the extracellular milieu and smaller compartments within the cell, these being separated spatially (by membranes) or functionally (carriers).

By changing the concentration of effectors (activators and inhibitors) in allosteric enzymes. By interacting with the allosteric site of the enzyme, such effectors can increase or decrease the enzyme activity on the basis of cooperative changes of conformation of the subunits, from which the enzyme is composed. The amount of the allosteric enzyme is not changed during the process.

By induction or repression when, in contrast with the two preceding mechanisms, the amount of enzyme and hence its total activity in the system is changed. The enzyme quantity per cell depends on presence of a repressor protein which is coded by a regulator gene and which, in its active form, inhibits the synthesis of some enzymes (repression). Some low-molecular weight compounds (inducers) can interact with the repressor and change it to an inactive form which cannot inhibit the synthesis of the given enzyme – this is the induction of their synthesis (derepression).

Fundamentally, no new metabolic pathways are opened but simply the existing ones are released or blocked, mainly on the feedback principle.

Multi-enzyme systems are those in which the individual enzymes are organized in such a way that the product of one enzyme reaction serves as substrate for the next. Here again, feedback regulation plays an important role, a product of a reaction sequence controlling the activity of one of the preceding enzymes, usually the first of the sequence. Feedback control is usually negative, i.e. in increased concentration of the product inhibits the regulatory enzyme. In multi-enzyme systems, one of the reactions appears to be rate-limiting, i.e. it proceeds at its maximum possible rate.

Regulation at the level of an organism requires the existence of special differentiated cells and structures with control function (nerve cells, endocrine glands). These cells are known to produce certain compounds that can be considered as material carriers of information, signals that are transported from one part of the organism to another.

Nervous regulation is mediated by a system of glial cells mutually interconnected through hollow and very long projections. It addresses itself to a special receptor, it is very rapid but it cannot embrace all cells of the organism. The molecular basis of this type of regulation are changes in ion concentrations inside and outside the nerve cells which initiate and propagate the transmission of nerve impulses. The impulse is transmitted to another cell at the end plate through molecular mediators.

The molecular basis of hormonal regulation are hormoneswhich can reach all cells of the organism and affect their function but only some cells (those of the target tissues) are receptive to the hormonal stimulus specifically. To increase the efficiency of regulation, hormones are often transported from the cell of origin to the target tissue in association with a specific protein. Such regulation is slower than the nervous one but it may affect any cell in the organism provided it has the proper receptor. It is assumed that the basic process of hormonal regulation is the binding of the hormone to a surface receptor protein or to a component of the cytoplasm.

The central nervous system is superior to the other parts of nervous communications as well as to hormonal regulation because it can store information transmitted by the signals into a memory, into specific structures of glial cells, and to use this information whenever necessary.

ESSENTIAL FATTY ACIDS

Polyunsaturated fatty acids with 20 carbon atoms exhibit unique physiological activities in the human body, for example lowering of cholesterol and triacylglycerols in plasma, prevention of atherosclerosis and other cardiovascular diseases and reduction of collagen-induced thrombocyte aggregation. Moreover, these fatty acids are of great value in the nutrition of edible marine animals reared in man-culture, and as precursors of eicosanoid hormones. Potential sources of such fatty acids include fungi, mainly lower Phyco-mycetes, microalgae, viz. dinoflagellates, diatoms and unicellular red algae, marine macroalgae, particularly Phaeophyta and Rhodophyta, and mosses. The biomass may be enriched with C₂₀-polyunsaturated fatty acids by chilling, nitrogen starvation, controlled illumination and incubation with lipophilic compounds.

Polyunsaturated fatty acids, especially those with 20 carbon atoms, are currently receiving attention in view of their physiological, industrial and pharmaceutical value. So far, these fatty acids are obtained from animals, e.g. fish oil, which makes their large-scale preparation rather uneconomical. Within the past decade much work has been done on polyunsaturated fatty acids in a variety of microorganisms and lower plants. The major objectives of the present article are to review these studies and discuss the biotechnological potential for providing an economical source of these valuable compounds.

The designation "essential" is related to mammals and, more precisely, to man. The mammalian route of fatty acid biosynthesis is more limited than that of plants and microorganisms. This is true as far as polymerization and desaturation reactions are concerned. Thus, it is known that condensation of C₂-units in mammals occurs only up to the С₁₈-stage. Furthermore, double bonds can be subsequently introduced at only four positions, Δ⁴, Δ⁵, Δ⁶ and Δ⁹. Mammals lack the ability to introduce any double bonds at carbon atoms between C-9 and the terminal methyl group. This implies that such living systems cannot synthesize linoleic (18:2 Δ⁹, Δ¹² or ω6; ω designates counting from the methyl group) and linolenic (18:3 Δ⁹, Δ¹², Δ¹⁵ or ω3) acids. These two fatty acids are however, needed by mammals, and must be supplied in their diet, hence the term "essential". Linoleic and linolenic acids belonging to the ω3-and ω6- families are used by mammals (and in fact many other biological systems) as precursors for the biosynthesis of C₂₀-polyunsaturated fatty acids, e.g. arachidonic acid (20:4). The latter fatty acid is important for mammals because it is used in turn as a starting material in the biosynthesis of several physiologically active signal molecules, namely the eicosanoid hormones. Linoleic and linolenic acids are very common in lipids of lower and higher plants, e.g. in oils from plant seeds. On the other hand, C₂₀-polyunsaturated fatty acids are extremely rare among seed-plants, but common among certain microorganisms and lower plants.

LITERATURE USED

Applied Microbiology and Biotechnology. Springer-Verlag, 1996.

Biotechnology Information Series. Worth Central Regional Extension Publication Iowa State University. March, 2001.

Philippine Daily Inquirer. August, 2004.

TIBTECH. January, 1999. Vol. 17.

A Working Paper for a Strategic Partnership with Canadian biotechnology. December, 2003.

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