Inactivation by liver

In model systems reflecting normal cooking conditions, a relatively weak mutagenic effect is exerted compared with that of HAAs. The type of mutagenic effect of these systems reflects base-pair in contrast to frameshift mutation, as caused by HAAs. Moreover, their action is effectively inactivated by liver chromosomal enzymes (S9 fraction), in contrast to HAAs, which require S9 activation to muta-genic/carcinogenic species.31... 

Trifluoroacetate dihydrate, C H N O.jS.CFjCOOH.-2H20, dec 180. [a] —56 (c — 0.2 in ethanol), uv max 278 nm (e I78O). Slowly loses activity when incubeted in blood. Inactivated by liver and kidney homogenates. 

Because of the metabolic lability of peptide bonds, metabolic inactivation is likely to play a particularly important role in the overall action of the peptide hormones. Structural alterations in the hormone molecule which increase metabolic stability would be expected to increase the duration of hormone action. Oxytocin is well known to be inactivated by an enzyme present in the serum of pregnant primates ( serum oxytocinase" see (1) but also more generally by homogenates of various tissues including the kidneys and liver. The major pathway of oxytocin inactivation by liver cell-sap has been shown to involve reductive fission of the disulphide bond followed by aminopeptidase degradation of the peptide chain (2). In an effort to obtain peptides resistant to aminopeptidase action we introduced D-hemicystine and N-methylhemicystine into the amino terminal position of... 

On the other hand, it has also been found (14) that 1-deamino-1-carba-oxytocin (Ib) is inactivated by liver homogenates, though very much more slowly than oxytocin. This finding demonstrates the existence of mechanisms other than disulphide reduction and aminopeptidase action capable of inactivating oxytocin-like peptides. The biochemical features and physiological significance of these mechanisms remain to be examined. 

Ascorbic acid is photosensitive and unstable in aqueous solution at room temperature. During storage of foods, vitamin C is inactivated by oxygen. This process is accelerated by heat and the presence of catalysts. Ascorbic acid concentration in human organs is highest in adrenal and pituitary glands, eye lens, liver, spleen, and brain. Potatoes, citrus fruits, blade currants, sea buckthorns, acerola, rose hips, and red paprika peppers are among the most valuable vitamin C sources [1,2]. 

The only other examples of bromoconduritol inhibition reported so far are a cytosolic jff-D-glucosidase from calf liver and the lysosomal ff-D-glu-cosidase from calf spleen. In spite of the 6500-fold difference in their reactivity with conduritol B epoxide (see Table XI), both enzymes are rapidly inactivated by bromoconduritol F, with kj(max)/Kj 10 M min for the cytosolic enzyme and lq(max)/Ki 3.2 10 for the crude and 3.9 10 M min for the purified lysosomal enzyme. It should be noted that purification of the lysosomal jS-D-glucosidase had effects on the reactivity with bromoconduritol F similar to those it had on the reactivity with conduritol B epoxide (see Table XI). 

The primary mechanism used by cholinergic synapses is enzymatic degradation. Acetylcholinesterase hydrolyzes acetylcholine to its components choline and acetate it is one of the fastest acting enzymes in the body and acetylcholine removal occurs in less than 1 msec. The most important mechanism for removal of norepinephrine from the neuroeffector junction is the reuptake of this neurotransmitter into the sympathetic neuron that released it. Norepinephrine may then be metabolized intraneuronally by monoamine oxidase (MAO). The circulating catecholamines — epinephrine and norepinephrine — are inactivated by catechol-O-methyltransferase (COMT) in the liver. 

The enzyme involved in the degradation of the dyes has been shown to be azoreductase. The enzymes were first isolated from the intestinal microflora and was later found to be produced by the cytosolic and microsomal fractions of the liver [47]. The enzyme was sensitive to oxygen and was inactivated by oxygen. In experiments involving intestinal anaerobic bacteria, Rafii et al. found the requirement of... 

Catalase and glutathione peroxidase provide two important cellular systems for eliminating H202. Catalase, a 56kDa cytosolic hemoprotein homotetramer that can act without a cofactor, although it may bind NAD(P)H, functions as a peroxidase to convert H202 to water. It can be irreversibly inactivated by oxidation and demonstrates decreased activity after ischemia-reperfusion. Catalase is more abundant in astrocytes than in neurons and in white matter than in gray matter, but it can be induced in neurons by neurotrophins. There is substantially less catalase activity in brain than in other tissues, such as liver. 

Two of these systems were studied as models—the acetylation of choline in brain to give acetyl choline (Hebb, Nachmansohn), and of sulfanilamide (the active component in prontosil, Chapter 3) in liver (Lipmann). Sulfanilamide is rapidly inactivated by acetylation on the p-amino group and then excreted. Sulfanilamide is easily diazotized the diazonium salt formed can be coupled with N-( 1 -naphthyl)ethylenedi-amine dihydrochloride to give a pink derivative (Bratton and Marshall, 1939). This formed the basis for an elegant colorimetric assay. Only the free p-amino group reacts, so that as acetylation proceeded color formation diminished. 

The most common way to take medications is by mouth (orally). This is the slowest and least efficient way to get medication into your system. When a tablet or capsule is swallowed, much of it either passes through the gastrointestinal tract without ever being absorbed into the bloodstream or is inactivated by the liver before it has a chance to reach the rest of the body (more on this later). The fastest and most efficient means to get medication into the bloodstream is to inject it directly into a vein (intravenously). If oral medication is so much slower and so much less efficient, then why do we usually take our medications by mouth We do so because it is easier, cheaper, safer, and painless to take medications orally. 

Isoniazid is bactericidal against growing M. tuberculosis. Its mechanism of action remains unclear. (In the bacterium it is converted to isonicotinic acid, which is membrane impermeable, hence likely to accumulate intracellu-larly.) Isoniazid is rapidly absorbed after oral administration. In the liver, it is inactivated by acetylation, the rate of which is genetically controlled and shows a characteristic distribution in different ethnic groups (fast vs. slow acetylators). Notable adverse effects are peripheral neuropathy, optic neuritis preventable by administration of vitamin Be (pyridoxine) hepatitis, jaundice. 

Each hormone is the center of a hormonal regulation system. Specialized glandular cells synthesize the hormone from precursors, store it in many cases, and release it into the bloodstream when needed (biosynthesis). For transport, the poorly water-soluble lipophilic hormones are bound to plasma proteins known as hormone carriers. To stop the effects of the hormone again, it is inactivated by enzymatic reactions, most of which take place in the liver (metabolism). Finally, the hormone and its metabolites are expelled via the excretory system, usually in the kidney (excretion). All of these processes affect the concentration of the hormone and thus contribute to regulation of the hormonal signal. 

Cytoplasmic and mitochondrial aldehyde dehydrogenases (from beef liver) have also been inactivated by the hydrate 21 [21]. 

Disposition Reteplase is primarily cleared by the liver and kidney. Animal studies suggest that reteplase is inactivated by blood components. 

Glucagon is extensively degraded in the liver and kidney as well as in plasma and at its tissue receptor sites. Because of its rapid inactivation by plasma, chilling of the collecting tubes and addition of inhibitors of proteolytic enzymes are necessary when samples of blood are collected for immunoassay of circulating glucagon. Its half-life in plasma is between 3 and 6 minutes, which is similar to that of insulin. 

Metabolism may be mediated by intestinal microflora, epithelial enzymes, or liver enzymes preceding entry into the systemic circulation. Chloramphenicol is well absorbed when administered orally to calves less than 1 week old, but it is inactivated by microflora when administered to ruminants. Similar observations have been made after oral administration of amoxicillin, ampicillin, and cephalexin therapy in young calves (11). On the other hand, trimethoprim, which is extensively metabolized in the liver and may undergo some metabolism in the rumen, shows higher systemic availability in the newborn calf and kid, due probably to the lower metabolic activity in the neonatal animal. 

Pharmacokinetic properties About 40% of the drug is absorbed from the intestinal tract but nearly completely inactivated by first pass metabolism in the liver (Killinger et al., 1979). The main metabolites are N-desmethyl-loperamide and the di-desmethyl derivative (Yoshida et al., 1979). The elimination half life is about 10 h. 

Protein C. This vitamin K-dependent glycoprotein serine protease zymogen is produced in the liver. It is an anticoagulant with species specificity (19—21). Protein C is activated to Protein Ca by thrombomodulin, a protein that resides on the surface of endothelial cells, plus thrombin in the presence of calcium. In its active form, Protein Ca selectively inactivates, by proteolytic degradation, Factors V, Va, VIII, and Villa. In this reaction the efficiency of Protein Ca is enhanced by complex formation with free Protein S. In addition, Protein Ca activates tissue plasminogen activator, which promotes the conversion of plasminogen [9001-91-6] to plasmin [9001-90-5]. 

A recent report describes the presence of pyrrolidone carboxylyl peptidase in rat liver (46). A partial purification of the enzyme has been obtained by ammonium sulfate fractionation and gel filtration on Sepha-dex G-200. The rat liver enzyme is similar to that obtained from Pseudomonas thus, it is protected against inactivation by 2-pyrrolidone and exhibits similar substrate specificity. 

The most notable similarities relate to activation and inactivation by metal ions and other materials. In most instances (Table I) each is activated by one or more of the cations Co2+, Mn2+, Ni2+, Mg2+, or Ca2+ of which the former three are usually most effective. Here again, however, there are differences. Thus, the B. atrox enzyme is not activated by ions, but they serve to reverse EDTA inhibition (23). The rat liver lysosomal enzyme is also not activated by divalent metals (SI) the sheep brain enzyme does not seem to require divalent cation and in fact it is inhibited by Co2+ (57). 

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