Rate of turnover

Let us fix attention on a particular H20 molecule A in the interior of water (if we wish to identify this molecule we can suppose that it contains a nucleus of the oxygen isotope 01S) and let us consider the water molecules which happen to be nearest neighbors of this molecule at the moment. These molecules have been in contact with A for different lengths of time. Since all the molecules in the liquid wander about, there was a time when none of these molecules was in contact with A. Further, if we could now begin to watch these molecules, we should find that, after the lapse of different periods of time, they become separated from A and each is replaced by another molecule. Similar remarks can be made about the molecules which come into contact with any chosen molecule. We can now raise the question—-What is the rate of turnover of this process The rate depends on the degree of local order and disorder, which in turn depends on the strength and character of the forces between adjacent molecules. 

From the rate of diffusion of radioactive Pb in molten lead, Andrade estimated that it takes an atom about 2 X 10 u second to move a distance equal to its own diameter.1 If the period of atomic vibration is 5 X 10 ,s second, this time is equivalent to idK)lit 40 atomic vibrations. From the considerations brought forward by Andrade, it appears that the same estimates would apply to liquid mercury above its melting point—that is, near room temperature. When we ask how often the particles of such a liquid change neighbors, it is clear that the rate of turnover is extremely large. If, for example, in (37) we set r0 equal to 1010 second, the chance that two particles remain in contact for as long as 7 X 10-10 second is less than one in a thousand. 

Important inherent characteristics of an enzyme that should be considered are the substrate affinity, characterized by the Michaelis constant the rate of turnover fecat> providing the catalytic efficiency fecat/ M. and the catalytic potential. Several attempts to compare enzyme catalysis with that of platinum have been published. Direct comparisons are difficult, because enzyme electrodes must be operated in aqueous electrolyte containing dissolved substrate, whereas precious metal electrodes aie often supplied with a humidified gaseous stream of fuel or oxidant, and produce water as steam. It is not straightforward to compare tme optimal turnover rates per active site, as it is often unclear how many active sites are being engaged in a film of enzyme on an electrode. 

All other things being equal, the rate of turnover of a particular substrate is directly proportional to the number (or the concentration) of enzyme molecules present. This is an important property to confirm during, for example, the development of a novel assay system. 

Attempts were also made to estimate the rate of turnover of the mucus gel. Telnet al. [14] measured the amount of mucus produced per time imit, using an in situ perfused intestinal loop model in the rat. They foimd that this turnover time is varying between 0.8 and 4.5 hr. 

The half-life is a precise indication of the rate of turnover. 

These three compounds exert many similar effects in nucleotide metabolism of chicks and rats [167]. They cause an increase of the liver RNA content and of the nucleotide content of the acid-soluble fraction in chicks [168], as well as an increase in rate of turnover of these polynucleotide structures [169,170]. Further experiments in chicks indicate that orotic acid, vitamin B12 and methionine exert a certain action on the activity of liver deoxyribonuclease, but have no effect on ribonuclease. Their effect is believed to be on the biosynthetic process rather than on catabolism [171]. Both orotic acid and vitamin Bu increase the levels of dihydrofolate reductase (EC 1.5.1.4), formyltetrahydrofolate synthetase and serine hydroxymethyl transferase in the chicken liver when added in diet. It is believed that orotic acid may act directly on the enzymes involved in the synthesis and interconversion of one-carbon folic acid derivatives [172]. The protein incorporation of serine, but not of leucine or methionine, is increased in the presence of either orotic acid or vitamin B12 [173]. In addition, these two compounds also exert a similar effect on the increased formate incorporation into the RNA of liver cell fractions in chicks [174—176]. It is therefore postulated that there may be a common role of orotic acid and vitamin Bj2 at the level of the transcription process in m-RNA biosynthesis [174—176]. 

If enzymes are described under tbe aspect of reaction mechanisms, the maximal rate of turnover Vmax. the Michaelis and Menten constant Km, the half maximal inhibitory concentration ICso, and tbe specific enzyme activity are keys of characterization of the biocatalyst. Even though enzymes are not catalysts in a strong chemical sense, because they often undergo an alteration of structure or chemical composition during a reaction cycle, theory of enzyme kinetics follows the theory of chemical catalysis. 

Therapeutically, irreversible antagonists present distinct advantages and disadvantages. Once the irreversible antagonist has occupied the receptor, it need not be present in unbound form to inhibit agonist responses. Consequently, the duration of action of such an irreversible antagonist is relatively independent of its own rate of elimination and more dependent on the rate of turnover of receptor molecules. 

A number of other interesting possibilities for utilizing the excess 14C in the atmosphere as a tracer of natural processes come easily to mind. Not much is known about the rate of turnover of humus in the soil. Measurements of 14C in soil humus over the next several years, while the terrestrial biosphere continues to fix carbon with significant amounts of excess 14C, should help to determine the rate of turnover of carbon in the reservoir of humus. Some work along these lines is already in progress (41). 

Rate of turnover In healthy adults, the total amount of protein in the body remains constant, because the rate of protein synthesis is just sufficient to replace the protein that is degraded. This process, called protein turnover, leads to the hydrolysis and resynthesis of 300 to 400 g of body protein each day. The rate of protein turnover varies widely for individual proteins. Short-lived proteins (for example, many regulatory proteins and misfolded proteins) are rapidly degraded, having half-lives measured in rrh-utes or hours. Long-lived proteins, with half-lives of days to weeks, constitute the majority of proteins in the cell. Structural proteins, such as collagen, are metabolically stable, and hare half-lives measured in months or years. 

Genetic factors influence the rate of not only synthesis of proteins but also their breakdown, i.e., the rate of turnover. As we have seen in Chapter 10, some enzymes are synthesized as inactive proenzymes which are later modified to active forms, and active enzymes are destroyed, both by accident and via deliberate hydrolytic pathways. Protein antienzymes may not only inhibit enzymes but may promote their breakdown.35 An example is the antienzyme that controls ornithine decarboxylase, a key enzyme in the synthesis of the polyamines that are essential to growth.36,37 As with all cell constituents, the synthesis of enzymes and other proteins is balanced by degradation. 

For modeling drug disposition in the eye following direct injection, the relative volumes of the aqueous spaces and the rates of turnover are important determinants of kinetics. Two spaces are clearly discernable as illustrated in Figure 23.5. 

It is doubtful that the data available justify quite such a sweeping statement. First, although the physiological functions of many compounds they mention are indeed unknown, it may not be fair to take them out of the context of metabolic pathways. They may be intermediates in the synthesis of pigments, hormones, or other compounds of known function. Conflicting reports on their rate of turnover exist. Second, the reviewers did not correlate plant chemistry specifically with feeding preference they simply assumed that taxonomically (basically that means morphologically) related plants would be similar in their chemical composition. In a very simple, direct way, the work of Brower (below) indicates that this assumption cannot be made. Third, we still need more cause-and-effect evidence for the relationship between plant... 

Rates of Turnover of 7 and / Phosphates of ATP If a small amount of ATP labeled with radioactive phosphorus in the terminal position, [7-32P]ATP, is added to a yeast extract, about half of the 32P activity is found in P, within a few minutes, but the concentration of ATP remains unchanged. 

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