Membranes enzymes

A very important issue - disregard of which is a big source of bad modeling studies - is the dear distinction of transport processes (toxicokinetics) and interactions with targets such as membranes, enzymes, or DNA (toxicodynamics). Figure 10.1-6 gives a rather simplified model of a fish to illustrate this distinction. 

The membrane enzyme luciferase, responsible for light emission in fireflies, is sensitive to anesthetics (20,21), and the concentrations of inhalational agents which inhibit luciferase are the same as those which cause general anesthesia. Studies of various classes of inhalational agents and luciferase demonstrated that above a certain chain length in a homologous series, a point is reached where higher members are not anesthetic. The same cut-off effect in efficacy is observed in anesthesia (22). This effect is not explainable by Hpid theory. 

In the glycerophosphate shuttle, two different glycerophosphate dehydrogenases, one in the cytoplasm and one on the outer face of the mitochondrial inner membrane, work together to carry electrons into the mitochondrial matrix (Figure 21.32). NADH produced in the cytosol transfers its electrons to dihydroxyaeetone phosphate, thus reducing it to glyeerol-3-phosphate. This metabolite is reoxidized by the FAD -dependent mitochondrial membrane enzyme to... 

Squalene monooxygenase, an enzyme bound to the endoplasmic reticulum, converts squalene to squalene-2,3-epoxide (Figure 25.35). This reaction employs FAD and NADPH as coenzymes and requires Og as well as a cytosolic protein called soluble protein activator. A second ER membrane enzyme, 2,3-oxidosqualene lanosterol cyclase, catalyzes the second reaction, which involves a succession of 1,2 shifts of hydride ions and methyl groups. 

TBT and TFT are membrane-active molecules, and their mechanism of action appears to be strongly dependent on organotin(IV) lipophilicity. They function as ionophores and produce hemolysis, release Ca(II) from sarcoplasmic reticulum, alter phosphatodylseiine-induced histamine release, alter mitochondrial membrane permeability and perturb membrane enzymes. Organotin(IV) compounds have been shown to affect cell signaling they activate protein kinase and increase free arachidonic acid through the activation of phospholipase... 

We described here the characterisation of the pemB gene and its product the second PME of E. chrysanthemi. The biochemical analysis of the purified protein indicated that PemB is actually an enzyme that demethylates pectin, leading to formation of methanol and PGA. However, PemB is more active on methylated oligogalacturonides than on polymeric pectin. The activating effect of non-ionic detergents on PemB was never pointed out for other pectinases and it is a characteristic of many membrane enzymes (21). 

Shanklin J, C Achim, H Schmidt, BG Fox, E Miinck (1997) Mossbauer studies of alkane w-hydroxylase evidence for a diiron cluster in an integral-membrane enzyme. Proc Natl Acad Sci USA 94 2981-2986. 

The pathway of the metabolic process converting the original nutrients, which are of rather complex composition, to the simple end products of COj and HjO is long and complicated and consists of a large number of intermediate steps. Many of them are associated with electron and proton (or hydrogen-atom) transfer from the reduced species of one redox system to the oxidized species of another redox system. These steps as a rule occur, not homogeneously (in the cytoplasm or intercellular solution) but at the surfaces of special protein molecules, the enzymes, which are built into the intracellular membranes. Enzymes function as specific catalysts for given steps. 

Dianzani, M.U., Paradisi, L., Barrera, G., Rossi, M.A. and Parola, M. (1989). The action of 4-hydroxynonenal on the plasma membrane enzymes from rat hepatocytes. In Free Radicals, Metal Ions and Biopolymers (eds. P.C. Neaumont, D.J. Deeble, B.J. Parsons and C. Rice-Evans) pp. 329-346. RicheUeu Press, London. 

Aminopeptidase A is another brush border membrane enzyme which has been the subject of various studies [79,81,83-86], It has been found in the intestinal brush border membrane of humans, rabbits, rats, and pigs and is active against peptides with acidic amino acids at the amino terminus. Its activity against dipeptides is more limited. Shoaf et al., isolated three rat brush border aminopeptidases with distinct but somewhat overlapping substrate specificities. These enzymes had preference for dipeptides containing methionine, arginine, or aspartic acid and glycine. The optimal pH for activity of aminopeptidase was reported to be 7-8. 

Animals and plants, especially roots and microorganisms, provide biochemical, bioorganic, and organic compounds to soil. These may be in the form of cellular components, such as cell walls, membranes, enzymes, and complex and simple organic compounds. Decomposition of complex cellular material and... 

PVA/chitosan blend membranes can be applied for the synthesis of monoglyceride, when used as a membrane enzyme reactor [277]. 

Changes in phospholipid composition between tiie inner and outer leaflets are brought about by die activity of a membrane enzyme known as a phospholipid translocase (or... 

Trypsinogen plays a key role among the proenzymes released by the pancreas. In the bowel, it is proteolytically converted into active trypsin (see p. 176) by enteropeptidase, a membrane enzyme on the surface of the en-terocytes. Trypsin then autocatalytically activates additional trypsinogen molecules and the other proenzymes (left). 

Figure 2. Behavior of membrane-associated lipases. From left to right (a) catalytic action of an enzyme that first requires attachment to the substrate at the water-membrane interface (b) action of an integral membrane enzyme that remains attached to the membrane where the enzyme finds its substrate (c) action of a membrane-bound enzyme on substrates in the aqueous medium and (d) action of an enzyme in the aqueous phase on a substrate that must first desorb from the membrane before it can interact with enzyme. From Jain et al. with permission of the authors.

Monoamine oxidases (MAOs) are mitochondrial membrane enzymes. These flavin-dependent enzymes are responsible for the oxidative deamination of numerous endogenic and exogenic amines (norepinephrine, serotonin, dopamine, etc.). MAO A and B take part in the regulation of these amines in many organs, such as the brain. The essential physiological role of these amines, especially in the central nervous system, has motivated the search for inhibitors of their catabolism in order to enhance the synaptic concentration of neuroamines. 

Mechanism of Action A proton pump inhibitor that selectively Inhibits the parietal cell membrane enzyme system (hydrogen-potassium adenosine triphosphatase) or proton pump. Therapeutic Effect Suppresses gastric acid secretion. Pharmacokinetics ... 

A cell s DNA is contained and protected by little compartments that are surrounded by membranes. Enzymes known as nucleases chop up any free DNA floating around the cell these enzymes act as cellular sentinels, guarding against invading viruses that try to sneak their genes into the cell. When an organism dies, the cellular membranes break down and nucleases destroy much of the cell s own DNA. Finding DNA in a body that has been around for a while is unlikely. 

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