Histidine inhibition

Feedback inhibition of the first enzyme in the pathway keeps the pathway adjusted to the availabihty of external histidine. When sufficient exogenous histidine is present, feedback inhibition completely stops the biosynthesis of histidine. Inhibition of the first enzyme by ADP and AMP adjusts the pathway to the energy charge status of the cell. Together, these repression and inhibition controls provide a complex circuitry by which the rate of histidine biosynthesis is correlated with the cell s needs and potential. 

L-Histidine inhibits the rate of synthesis of compound III and as a consequence, of aminoribosylimidazolecarboxamide phosphate. Glutamine is essential for the conversion of compound III to the latter and it will stimulate this conversion even in the presence of histidine. 

Able to form Ag salt of lower solubility than AgQ in H2O. Therefore applications in photographic processes Inhibition of histidine decarboxylase activity Antifoggant for color films Anthelmintic activity Quenching for oil composition caialj si for the industrial isomerization of cis a, (3 unsaturaied carboxylic acids rubber vul-cankzate improver... 

The high affinity LBS is involved in the interaction of plasminogen with fibrin, a2-antiplasmin, and a plasmin inhibitor called histidine-rich glycoprotein. It has been observed that plasminogen activation takes place on the surface of fibrin and that a2-antiplasmin competitively inhibits the plasminogen—fibrin interaction at the high affinity LBS. 

Histamine synthesis from 1-histidine can be selectively inhibited by a-fluoromethylhistidine. Metabolism by... 

Treatment of bovine heart bci complex with ethoxyformic anhydride (EFA), which is known to modify amino acid residues covalently (preferentially histidine residues), inhibits electron transfer and has an effect on the EPR spectra of the Rieske cluster comparable to that observed upon addition of stigmatellin, that is, a decrease in rhombicity (80). This further supports the suggestion that quinones as well as quinonoid inhibitors interact directly with the histidine ligands of the Rieske cluster. 

A different type of reactive bromo compound having a moderate resemblance to hexoses is represented by the bromoconduritols B (40) and F (41), named after the respective parent tetrahydroxycyclohexene. Even thou their hydroxylation pattern resembles that of D-glucose, only a few examples of D-glucosidase inhibition have been reported. The first was a-D-glucosi-dase from yeast, which is inhibited by bromoconduritol B (formerly called bromoconduritol A), having ki(max)/Kj 69,000 M" min", by alkylation of a histidine residue at the active site. 

Decarboxylation of histidine to histamine is catalyzed by a broad-specificity aromatic L-amino acid decarboxylase that also catalyzes the decarboxylation of dopa, 5-hy-droxytryptophan, phenylalanine, tyrosine, and tryptophan. a-Methyl amino acids, which inhibit decarboxylase activity, find appfication as antihypertensive agents. Histidine compounds present in the human body include ergothioneine, carnosine, and dietary anserine (Figure 31-2). Urinary levels of 3-methylhistidine are unusually low in patients with Wilson s disease. 

Histamine is synthesised by decarboxylation of histidine, its amino-acid precursor, by the specific enzyme histidine decarboxylase, which like glutaminic acid decarboxylase requires pyridoxal phosphate as co-factor. Histidine is a poor substrate for the L-amino-acid decarboxylase responsible for DA and NA synthesis. The synthesis of histamine in the brain can be increased by the administration of histidine, so its decarboxylase is presumably not saturated normally, but it can be inhibited by a fluoromethylhistidine. No high-affinity neuronal uptake has been demonstrated for histamine although after initial metabolism by histamine A-methyl transferase to 3-methylhistamine, it is deaminated by intraneuronal MAOb to 3-methylimidazole acetic acid (Fig. 13.4). A Ca +-dependent KCl-induced release of histamine has been demonstrated by microdialysis in the rat hypothalamus (Russell et al. 1990) but its overflow in some areas, such as the striatum, is neither increased by KCl nor reduced by tetradotoxin and probably comes from mast cells. 

The rate of phosphoprotein formation in the presence of 5 mM CaCl2 was only slightly affected by mild photooxidation in the presence of Rose Bengal, but the hydrolysis of phosphoenzyme intermediate was inhibited sufficiently to account for the inhibition of ATP hydrolysis [359]. The extent of inhibition was similar whether the turnover of E P was followed after chelation of Ca with EGTA, or after the addition of large excess of unlabeled ATP. These observations point to the participation of functionally important histidine residues in the hydrolysis of phosphoprotein intermediate [359]. 

Similarly, the rate of inhibition of phosphoenzyme formation by diethylpyrocarbonate (DEPC) was much slower than the loss of ATPase activity [368], Even when the reaction approached completion with more than 90% inhibition of ATP hydrolysis, about 70% of the Ca -ATPase could still be phosphorylated by ATP (2.3nmoles of E P/mg protein). The remaining 30% of E P formation and the corresponding ATPase activity was not reactivated by hydroxylamine treatment, suggesting some side reaction with other amino acids, presumably lysine. When the reaction of the DEPC-modified ATPase with P-ATP was quenched by histidine buffer (pH 7.8) the P-phosphoenzyme was found to be exceptionally stable under the same conditions where the phosphoenzyme formed by the native ATPase underwent rapid hydrolysis [368]. The nearly normal phosphorylation of the DEPC-trea-ted enzyme by P-ATP implies that the ATP binding site is not affected by the modification, and the inhibition of ATPase activity is due to inhibition of the hydrolysis of the phosphoenzyme intermediate [368]. This is in contrast to an earlier report by Tenu et al. [367], that attributed the inhibition of ATPase activity by... 

After the nucleophilic attack by the hydroxyl function of the active serine on the carbonyl group of the lactone, the formation of the acyl-enzyme unmasks a reactive hydroxybenzyl derivative and then the corresponding QM. The cyclic structure of the inhibitor prevents the QM from rapidly diffusing out of the active center. Substitution of a second nucleophile leads to an irreversible inhibition. The second nucleophile was shown to be a histidine residue in a-chymotrypsin28 and in urokinase.39 Thus, the action of a functionalized dihydrocoumarin results in the cross-linking of two of the most important residues of the protease catalytic triad. 

Irreversible inhibition is probably due to the alkylation of a histidine residue.43 Chymotrypsin is selectively inactivated with no or poor inhibition of human leukocyte elastase (HLE) with a major difference the inactivation of HLE is transient.42,43 The calculated intrinsic reactivity of the coumarin derivatives, using a model of a nucleophilic reaction between the ligand and the methanol-water pair, indicates that the inhibitor potency cannot be explained solely by differences in the reactivity of the lactonic carbonyl group toward the nucleophilic attack 43 Studies on pyridyl esters of 6-(chloromethyl)-2-oxo-2//-1 -benzopyran-3-carboxylic acid (5 and 6, Fig. 11.5) and related structures having various substituents at the 6-position (7, Fig. 11.5) revealed that compounds 5 and 6 are powerful inhibitors of human leukocyte elastase and a-chymotrypsin thrombin is inhibited in some cases whereas trypsin is not inhibited.21... 

Histamine is synthesized in the brain from L-histidine by the enzyme histidine decarboxylase (HDC) (Fig. 2.2C). HDC can be inhibited by application of a-fluoromethylhistidine (a-FMH). Unlike serotonin and the catecholamines, no... 

There are two distinct pools of HA in the brain (1) the neuronal pool and (2) the non-neuronal pool, mainly contributed by the mast cells. The turnover of HA in mast cells is slower than in neurons it is believed that the HA contribution from the mast cells is limited and that almost all brain histaminergic actions are the result of HA released by neurons (Haas Panula, 2003). The blood-brain barrier is impermeable to HA. HA in the brain is formed from L-histidine, an essential amino acid. HA synthesis occurs in two steps (1) neuronal uptake of L-histidine by L-amino acid transporters and (2) subsequent decarboxylation of l-histidine by a specific enzyme, L-histidine decarboxylase (E.C. 4.1.1.22). It appears that the availability of L-histidine is the rate-limiting step for the synthesis of HA. The enzyme HDC is selective for L-histidine and its activity displays circadian fluctuations (Orr Quay, 1975). HA synthesis can be reduced by inhibition of the enzyme HDC. a-Fluoromethylhistidine (a-FMH) is an irreversible and a highly selective inhibitor of HDC a single systemic injection of a-FMH (10-50 mg/kg) can produce up to 90% inhibition of HDC activity within 60-120 min (Monti, 1993). Once synthesized, HA is taken up into vesicles by the vesicular monoamine transporter and is stored until released. 

Thus, the mechanism of MT antioxidant activity might be connected with the possible antioxidant effect of zinc. Zinc is a nontransition metal and therefore, its participation in redox processes is not really expected. The simplest mechanism of zinc antioxidant activity is the competition with transition metal ions capable of initiating free radical-mediated processes. For example, it has recently been shown [342] that zinc inhibited copper- and iron-initiated liposomal peroxidation but had no effect on peroxidative processes initiated by free radicals and peroxynitrite. These findings contradict the earlier results obtained by Coassin et al. [343] who found no inhibitory effects of zinc on microsomal lipid peroxidation in contrast to the inhibitory effects of manganese and cobalt. Yeomans et al. [344] showed that the zinc-histidine complex is able to inhibit copper-induced LDL oxidation, but the antioxidant effect of this complex obviously depended on histidine and not zinc because zinc sulfate was ineffective. We proposed another mode of possible antioxidant effect of zinc [345], It has been found that Zn and Mg aspartates inhibited oxygen radical production by xanthine oxidase, NADPH oxidase, and human blood leukocytes. The antioxidant effect of these salts supposedly was a consequence of the acceleration of spontaneous superoxide dismutation due to increasing medium acidity. 

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