Biochemical mechanisms

During the 1950s, an era when biochemical knowledge developed very fast, there was a very strong belief that by finding the biochemical mechanism for resistance, it should be easy to find some substance that counteracted it, for instance, inhibitors of enzymes that detoxicate the pesticide or a new pesticide that shows higher activity toward the resistant insects. 

A priori, i.e., without doing any empirical research, the following mechanisms have been postulated for insect resistance to insecticides. Most of the points also apply to weeds and fungi  

Behavior Insects may have modified their behavior so that they avoid the areas sprayed with the insecticide. Such behavior may be genetically determined. 

Reduced penetration of the pesticide through the cuticle or the intestine. 

Lowered bioactivation Some pesticides such as the sulfur-containing organophosphates may often be bioactivated. 

AquaporinS arc on the small side, consist of about 260 amino acids, and have a molecular weight of about 30 kDa. They weave six times in or out of the plasma membrane (Preston eta ., 1994 Rainaff af., 1995 Deen al., 1994). The aquaporins are related to each other, and constitute a family of proteins. This means that if one were to line up all the polypeptides, one on top of the other, one would find that about half of all amino acids occur at identical positions, when viewing their order from the N terminus to the C terminus. The technical term for measuring relatedness in any protein is sequence homology, 

Aquaporin-1 (AQP-l) and AQF-3 are used for basal water transport in many tissues. The term constitutive is used to refer to any basal activity. The term regulated is used to refer to any acbvity that is increased or decreased by hormones or other components of the environment. AQP-5 is required to produce the water in tears and saliva. AQP-4 occurs in the brain, where it is used in the mechanism that senses if one needs to drink more or less water 

Further details on renal physiology and water regulation appear in the Sodium, Potassium, Chloride, and Water section. 

The process of digestion and the activity of carbonic anhydrase are major ev cryday concerns in the medical profession. A clearer understanding of the concepts of protein digestion and carbonic anhydrase acti ity is provid by simplified descriptions of the relevant biochemical mechanisms. Protein digestion involves the addition of water to a peptide bond. Carbonic anhydrase activity involves the addition of water to COj. A related process, the phosphorolysis of glycogen, is also described. 

Hydrolysis means the reaction of a molecule of water with a chemical bond that results in the breaking of that bond. The process of hydrolysis results in the lysis 

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As a class of compounds, the two main toxicity concerns for nitriles are acute lethality and osteolathyrsm. A comprehensive review of the toxicity of nitriles, including detailed discussion of biochemical mechanisms of toxicity and stmcture-activity relationships, is available (12). Nitriles vary broadly in their abiUty to cause acute lethaUty and subde differences in stmcture can greatly affect toxic potency. The biochemical basis of their acute toxicity is related to their metaboHsm in the body. Following exposure and absorption, nitriles are metabolized by cytochrome p450 enzymes in the Hver. The metaboHsm involves initial hydrogen abstraction resulting in the formation of a carbon radical, followed by hydroxylation of the carbon radical. MetaboHsm at the carbon atom adjacent (alpha) to the cyano group would yield a cyanohydrin metaboHte, which decomposes readily in the body to produce cyanide. Hydroxylation at other carbon positions in the nitrile does not result in cyanide release. 

Biochemistry resulted from the early elucidation of the pathway of enzymatic conversion of glucose to ethanol by yeasts and its relation to carbohydrate metaboHsm in animals. The word enzyme means "in yeast," and the earfler word ferment has an obvious connection. Partly because of the importance of wine and related products and partly because yeasts are relatively easily studied, yeasts and fermentation were important in early scientific development and stiU figure widely in studies of biochemical mechanisms, genetic control, cell characteristics, etc. Fermentation yeast was the first eukaryote to have its genome elucidated. 

In the presence of calcium, the primary contractile protein, myosin, is phosphorylated by the myosin light-chain kinase initiating the subsequent actin-activation of the myosin adenosine triphosphate activity and resulting in muscle contraction. Removal of calcium inactivates the kinase and allows the myosin light chain to dephosphorylate myosin which results in muscle relaxation. Therefore the general biochemical mechanism for the muscle contractile process is dependent on the avaUabUity of a sufficient intraceUular calcium concentration. 

To describe the biochemical mechanisms that cause health effects... 

The biochemical mechanism of bacterial luminescence has been studied in detail and reviewed by several authors (Hastings and Nealson, 1977 Ziegler and Baldwin, 1981 Lee et al., 1991 Baldwin and Ziegler, 1992 Tu and Mager, 1995). Bacterial luciferase catalyzes the oxidation of a long-chain aldehyde and FMNH2 with molecular oxygen, thus the enzyme can be viewed as a mixed function oxidase. The main steps of the luciferase-catalyzed luminescence are shown in Fig. 2.1. Many details of this scheme have been experimentally confirmed. 

According to their genetic relationship and their biochemical mechanism of action (3-lactamases are divided into enzymes of the serine-protease type containing an active-site serine (molecular class A, C, and D enzymes) and those of the metallo-protease type (molecular class B enzymes), which contain a complex bound zinc ion. 

BH3 domain) of the BH3-only proteins binds to other Bcl-2 family members thereby influencing their conformation. This interaction facilitates the release of cytochrome C and other mitochondrial proteins from the intermembrane space of mitochondria. Despite much effort the exact biochemical mechanism which governs this release is not yet fully understood. The release of cytochrome C facilitates the formation of the apoptosome, the second platform for apoptosis initiation besides the DISC. At the apoptosome which is also a multi-protein complex the initiator caspase-9 is activated. At this point the two pathways converge. 

The basic biochemical mechanisms leading to bacterial resistance can be classified into three different categories. 

Chambers JE, Carr RE. 1995. Biochemical mechanisms contributing to species differences in insecticidal toxicity. Toxicology 105 291-304. 

Other mnch more toxic componnds operating throngh specific biochemical mechanisms (e.g., OP anticholinesterases) cannot be modeled in this way. If... 

Biochemical mechanism of resistance to aminoglycosidic antibiotics, H. Umezawa, Adv. Carbohydr. Chem. Biochem., 30 (1974) 183-225. 

The prominent role played by Japanese investigators in carbohydrate science is underscored by the two substantial chapters by Japanese authors in the current volume. This volume also pays tribute to one of the greatest Japanese carbohydrate scientists, Hamao Umezawa, in the obituary article contributed by Tsuchiya, Maeda, and Horton. Hamao Umezawa dedicated his entire, extraordinarily productive career to the development of antibiotics his innovative contributions are exemplified by his chapter in Volume 30 of this series on the biochemical mechanism of inactivation of aminoglycoside antibiotics. 

Table 1-2. The major causes of diseases. All of the causes listed act by influencing the various biochemical mechanisms in the cell or in the body. ...

Kroll MH, Schafer Al Biochemical mechanisms of platelet activation. Blood 1989 74 1181. 

E---S + R E---P->E + P The enzyme is regenerated at the end of this sequence, making it available to bind another substrate molecule. Note that the steps in this enzyme-catalyzed biochemical mechanism are similar to the steps in chemical heterogeneous catalysis binding with bond weakening, reaction at the bound site, and release of products. 

Biochemical mechanisms of resistance 3.5 Multidrug resistance pumps... 

The following sections describe the biochemical mechanisms of resistance to different classes of antibiotics, with the antibiotics grouped according to their mechanism of action. 

Commandeur JNM, Vermeulen NPE. 1990b. Molecular and biochemical mechanisms of chemically induced nephrotoxicity A review (invited review). Chem Res Toxicol 3 171-194. 

Phytochemicals have little nutritional value and do not get absorbed in the body, but they seem to turn on certain switches in the biochemical mechanisms, which signal the beneficial pathways to maintain health, and to turn off the switches which proceed to adverse biochemical pathways. Rice bran products have demonstrated significant benefits as nutritional therapies in diabetes, hyperlipidemia, cancer, fatty liver, hypercalcuria and heart disease. There is experimental and clinical evidence for the beneficial health effects of the following bioactives of rice bran ... 

The above scientific information on rice bran phytochemicals indicates that a multitude of mechanisms are operating at the cellular level to bring about specific health effects. Several health benefits of rice bran appear to be the result of the synergistic function of the many phytochemicals, antioxidants, vitamins and minerals which operates through a specific immune response. Their role in the biochemical mechanisms at the cellular level which result in major health effects is shown in Fig. 17.1. A short overview summarizing the effect of the various phytochemicals on major health issues such as cancer, immune function, cardiovascular disease, diabetes, altered liver function and gastrointestinal and colon disease will be given below. 

Chearwae, W. et al.. Biochemical mechanism of modulation of human P-glycoprotein (ABCBl) by curcumin 1, 11, and III purified from turmeric powder, Biochem. Pharmacol., 68, 2043, 2004. 

Although single-electron-transfer (SET) processes would be expected to be important in reactions that use metals as reagents, this type of process has also been recognized in the reduction of carbonyl groups that involve 1,4-dihydronicotinamide derivatives . Recent work by Oae and coworkers" has shown that an SET process is operative in the reduction of dibenzothiophene S-oxide by l-benzyl-l,4-dihydronicotinamide when the reaction is catalyzed by metalloporphins. The reaction is outlined in equation (18), but the study gave results of much more mechanistic than synthetic value. This type of study is relevant to understanding biochemical mechanisms since it is known that methionine sulphoxide is reduced to methionine by NADPH when the reaction is catalyzed by an enzyme isolated from certain yeasts . 

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