Affects Many Enzymes

Affects many enzyme systems, including those critical to heme synthesis, those that maintain cell membranes, and those involved with steroid metabolism. 

In addition to these we need to mention a small group of metabolites that belong structurally with the building blocks of nucleic acids but which have major metabolic functions that are quite separate from their relationship to nucleic acids. These are the adenosine phosphates two of these, adenosine 5 -triphosphate and adenosine 5 -diphosphate, participate in many metabolic reactions (more, indeed, than any other substance, aside from water) a third, adenosine 5 -monophosphate, participates in relatively few reactions but affects many enzymes as an inhibitor or as an activator. These names are cumbersome for everyday use and biochemists refer to them nearly aU of the time as ATP, ADP, and AMP, respectively. In animals, the ATP needed for driving all the functions of the cell is generated in small compartments of cells called mitochondria. For the purposes of this book we shall not need to know any details of how mitochondria fulfill their functions, but we do need to know that they exist, because we shall meet them again in a quite different context it turns out that in most organisms mitochondria contain small amounts of their own DNA, and this allows some special kinds of analyses. Adenosine, the skeleton from which ATP, ADP, and AMP are built, has a separate importance as one of the four bases that define the sequence of DNA. 

Insulin also affects many enzymes. In general insulin puts the body into an anabolic state, stimulating the production of glycogen and fat and inhibiting the use of glycogen and breakdown of fat. 

At the present time, we can cite more examples of enzyme modification occurring as regulatory mechanisms in animal metabolism than we can in microbial metabolism. In animal metabolism, phosphorylation by protein kinases affects many enzymes (13). 

Metabolic Functions. The functions of the thyroid hormones and thus of iodine are control of energy transductions (121). These hormones increase oxygen consumption and basal metaboHc rate by accelerating reactions in nearly all cells of the body. A part of this effect is attributed to increase in activity of many enzymes. Additionally, protein synthesis is affected by the thyroid hormones (121,122). 

Many herbicides and other chemicals have been reported to influence levels of various phenolic compounds in higher plants by unknown mechanisms. It is unlikely that more than a few of these compounds have a primary influence on secondary phenolic compound synthesis. For instance, in our survey of the effects of 17 herbicides on anthocyanin accumulation, only glyphosate appeared to directly influence accumulation (31). The effects of several compounds on secondary phenolic compound production for which the mechanism of influence is unknown are summarized in Table II. A much longer list could be derived from the literature. Unfortunately, many of these compounds are phytotoxic or are known to have effects other than on secondary aromatic compound production. In most cases the effects on these compounds correlate well with extractable PAL activity (31, 71, 72, 73, 74) (Figure 5), even though they do not directly affect the enzyme. 

The Li+-induced inhibition of the production of the HSV virus may be related to its actions upon viral DNA polymerase production and activity. Li+ reduces both the synthesis of DNA polymerase in tissue culture and the activity of DNA polymerase in vitro, each by about 50%. It has been proposed that Li+ reduces the biosynthesis of viral polypeptides and nucleic acids, and hence inhibits viral DNA replication by competition with Mg2+, a cofactor of many enzymes [243]. However, the inhibitory effect of Li+ on HSV replication in tissue culture is not affected by Mg2+ levels. A more likely hypothesis is the alteration of the intracellular K+ levels, possibly modifying levels of the high-energy phosphate compounds by replacement of either Na+ or K+ in Na+/K+-ATPase [244]. In tissue culture, HSV replication has been shown to be affected by the... 

The subject of biochemical reactions is very broad, covering both cellular and enzymatic processes. While there are some similarities between enzyme kinetics and the kinetics of cell growth, cell-growth kinetics tend to be much more complex, and are subject to regulation by a wide variety of external agents. The enzymatic production of a species via enzymes in cells is inherently a complex, coupled process, affected by the activity of the enzyme, the quantity of the enzyme, and the quantity and viability of the available cells. In this chapter, we focus solely on the kinetics of enzyme reactions, without considering the source of the enzyme or other cellular processes. For our purpose, we consider the enzyme to be readily available in a relatively pure form, off the shelf, as many enzymes are. 

Because many other chemicals can affect the enzymes responsible for n-hexane metabolism (see Section 2.3.3, Metabolism), the possibility of interactions is a significant concern. The initial step in n-hexane metabolism is oxidation to a hexanol by a cytochrome P-450 isozyme other chemicals can induce these enzymes, possibly increasing the rate of metabolism to the neurotoxic 2,5-hexanedione, or competing with M-hexanc and its metabolites at enzyme active sites, reducing the rate of metabolism. Interactive effects can be concentration and/or duration dependent. 

Oxygen is a substrate for enzymes located in every cell of the body and, since the corresponding participating enzymes are not of the same efficiency in different individuals, variability in the effects of oxygen lack should be expected. As Nims says "It is obvious that anoxia affects many functions and that these are not affected in the same degree from one individual to another. "21... 

The answer is C. Thymine dimers are repaired by the process of nucleotide excision repair, which involves many enzyme activities that recognize the mutated structure, cut the DNA strand on both sides of the mutation, remove (excise) the affected fragment, and then refill the gap. One of the major genes leading to xeroderma pigmentosoum encodes a specific excinuclease. 

The activities of many enzymes vary with pH in the same way that simple acids and bases ionize. This is not surprising, since, as we saw in Chapter 1, the active sites generally contain important acidic or basic groups (Table 5.1). It is to be expected that if only one protonic form of the acid or base is catalyti-cally active, the catalysis will somehow depend on the concentration of the active form. In this chapter we shall see that kcM, KM, and kcJKM are affected in different ways by the ionizations of the enzyme and enzyme-substrate complex. 

The effect of pH and ions on acid DNase activity has been investigated in several laboratories, and rather different results have been reported. It appears now that many discrepancies result from a rather poor understanding of the complexity of pH and ion effects. In fact, it has been shown (34) that electrolytes and pH modify the acid DNase activity not only by affecting the enzyme itself but also by stabilizing or destabilizing the secondary structure of native DNA. Since the enzyme has a quite different affinity for the native vs. the denatured structure... 

In addition to direct effects on genes regulating inflammation, glucocorticoids also inhibit the transcription factors that initiate synthesis of pro-inflammatory cytokines (e.g., interleukin-1, tumor necrosis factor), enzymes (e.g., COX-2, nitric oxide synthase), and receptor proteins (e.g., natural killer receptors).17,87,89 Glucocorticoids may also exert some of their effects via a membrane-bound receptor that regulates activity of macrophages, eosinophils, T lymphocytes, and several other types of cells involved in the inflammatory response.89 Consequently, glucocorticoids affect many aspects of inflammation, and their powerful anti-inflammatory effects in rheumatoid arthritis result from their ability to blunt various cellular and chemical components of the inflammatory response. 

Because xenobiotic metabolism involves many enzymes with different cofactor requirements, prosthetic groups, or endogenous cosubstrates, it is apparent that many different nutrients are involved in their function and maintenance. Determination of the effects of deficiencies, however, is more complex because reductions in activity of any particular enzyme will be effective only if it affects a change in a rate-limiting step in a process. In the case of multiple deficiencies, the nature of the rate-limiting step may change with time... 

Like cadmium, mercury(II) has a strong affinity for sulfhydryl groups in proteins, enzymes, hemoglobin, and serum albumin. Because of the abundance of sulfhydryl groups in active sites of many enzymes, it is difficult to establish exactly which enzymes are affected by mercury in biological systems. 

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