Disease relevance of p-Chloromercuribenzoic acid

• Unlike other beta-class eukaryotic DNA polymerases, the enzyme purified from the Novikoff hepatoma is inhibited by both sulfhydryl blocking agents N-ethylmaleimide (NEM) and p-hydroxymercuribenzoate (pHMB) [1].
• Accumulation of cimetidine was against a concentration gradient via a saturable process (Km = 53 microM, Vmax = 12 nmol/ml/min) that was inhibited by sulfhydryl reagents (p-hydroxymercuribenzoate), metabolic inhibitors (KCN and 2,4-dinitrophenol) and hypothermia (Q10 = 4.5), but did not require inward Na+ gradient [2].
• Incubation of Novikoff rat hepatoma cells; mouse L929, P388 and L1210 cells; and Chinese hamster ovary cells with sulfhydryl reagents, such as p-hydroxymercuribenzoate or p-hydroxymercuribenzenesulfonate, reduced the zero-trans influx of uridine in a concentration-dependent manner [3].
• The reactivity of the sulfhydryl groups of histidyl-t RNA synthetase from Salmonella typhimurium and the effect of substrates on the reactivity has been studied using p-hydroxymercuribenzoate and 5, 5'-dithiobis (2-nitrobenzoic acid) as reagents [4].
• Hyperglycemia following p-hydroxymercuribenzoate administration to mice [5].

High impact information on p-Chloromercuribenzoic acid

• N-ethylmaleimide, p-hydroxymercuribenzoate, and mersalyl acid also blocked reactivation of both the rotary axostyle and flagella [6].
• Treatment of the angiogenin-PRI complex with p-hydroxymercuribenzoate releases enzymatically active angiogenin [7].
• When human kidney hexosaminidase A was dissociated into its subunits by p-hydroxymercuribenzoate, three distinct proteins having isoelectric points of pH 7.2.5.4, and 4.3 were isolated [8].
• It is concluded that p-hydroxymercuribenzoate dissociates hexosaminidase A, (alphabeta)3, into its subunits, and the beta subunits can reassociate to form relatively stable hexosaminidase B, (betabeta)3, while the alpha subunits reassociate in both the dimeric state, alpha2, and a polymeric state, alpha8 [8].
• Pyrophosphate-driven proton translocation was stimulated by potassium ions and inhibited by KF, by the pyrophosphate analogs imidodiphosphate and aminomethylenediphosphonate (AMDP), and by the thiol reagent p-hydroxymercuribenzoate at concentrations similar to those that inhibit the plant vacuolar H(+)-pyrophosphatase (PPase) [9].

Biological context of p-Chloromercuribenzoic acid

• Another residue, cysteinyl 46, which is thought to be in the active site, is much more reactive toward p-hydroxymercuribenzoate in the mutant subunit than in the wild type protein [10].
• The incubation of hemolysates with iodoacetate (5-100 mm), N-ethylmaleimide (0.1-10 mm), or p-hydroxymercuribenzoate (0.1-5 mm) mimicked the effect of oxidative stress on AMP-deaminase, indicating that sulfhydryl group modification is involved in the enzyme activation [11].
• On the other hand, p-hydroxymercuribenzoate-treated canatoxin was still lethal to mice, and both treated proteins were fully active in promoting platelet aggregation and binding to glycoconjugates [12].
• It was less toxic to cells grown chemoheterotrophically in the dark or photoheterotrophically in the presence of 3-(3,4-dichlorophenyl)-1,1-dimethylurea. p-Hydroxymercuribenzoate therefore killed only cells which were performing photosynthesis at high rates, thereby specifically selecting for mutants deficient in this process [13].
• The two peaks differed in their response to Mn(2+), substrate specificity, heat stability and inhibition by p-hydroxymercuribenzoate [14].

Anatomical context of p-Chloromercuribenzoic acid

• Since p-hydroxymercuribenzoate, which is known to be impermeable to the inner mitochondrial membrane, inhibits glutaminase similarly to NEM, phosphate-activated glutaminase is assumed to be compartmentalized within the inner mitochondrial membrane [15].
• Rabbit erythrocyte GR exhibited substrate inhibition, and was susceptible to inhibition by p-hydroxymercuribenzoate under certain conditions [16].
• 8R-hydroperoxy-9Z,12Z-octadecadienoic acid was isolated from incubations of linoleic acid with the partially purified enzyme or with the cytosol in the presence of p-hydroxymercuribenzoate [17].
• Pretreatment of the microsomes with p-hydroxymercuribenzoate, a sulfhydryl-blocking agent and an inhibitor of PGH2----PGE2 isomerase, did not limit lens microsomal PGE2 formation (24% vs. 39%) but dramatically inhibited PGF2 alpha production (25% vs. 6%) [18].
• The serine protease inhibitors, L-1-tosylamide-2-phenylethyl-chloromethyl ketone (TPCK) and N-alpha-p-tosyl-L-lysine-chloromethyl ketone (TPCK) as well as an inhibitor of thiol protease activity, p-hydroxymercuribenzoate (PHMB), suppressed granule enzyme release from neutrophils activated with IL-1 [19].

Associations of p-Chloromercuribenzoic acid with other chemical compounds

• The inhibition of shikimate kinase activity by p-hydroxymercuribenzoate is reversed completely when the enzyme complex is treated with dithiothreitol, suggesting the sulfhydryl groups may be involved with the active site [20].
• Inhibition of protein binding by pyridoxal 5'-phosphate and NaBH4 suggested a role for lysine at the DNA binding site, while sulfhydryl group involvement was indicated by the sensitivity of the protein to p-hydroxymercuribenzoate inhibition [21].
• Nitrate and NO2- transport by roots of 8-day-old uninduced and induced intact barley (Hordeum vulgare L. var CM 72) seedlings were compared to kinetic patterns, reciprocal inhibition of the transport systems, and the effect of the inhibitor, p-hydroxymercuribenzoate [22].
• The interactions of cis- and trans-Pt(NH3)2Cl2 with the enzyme's sulfhydryl (-SH) groups were inferred from the results of spectrophotometric titrations of the enzyme with 5,5'-dithiobis(2-nitrobenzoic acid) and p-hydroxymercuribenzoate [23].
• The thiolate-specific alkylating agent N-ethylmaleimide (NEM) as well as the reversible thiol-specific blockers p-hydroxymercuribenzoic acid (PHMB) and mersalyl acid inhibited PrP(Sc) amplification in vitro, indicating that the conformational change from PrP(C) to PrP(Sc) requires a thiol-containing factor [24].

Gene context of p-Chloromercuribenzoic acid

• 0. Two 25-kDa and 18-kDa RNases, which were obtained from human liver using a cellulose phosphate column, were bound to the immobilized RNase inhibitor and recovered in a pure and active form after treatment of the resin with p-hydroxymercuribenzoate [25].
• All purified lecithin-cholesterol acyltransferase species were activated by human apolipoprotein A-I and were similarly inhibited by p-hydroxymercuribenzoate and phenylmethylsulfonyl fluoride [26].
• Reaction of the sulfhydryl by titration with PHMB or DTNB leads to loss of sweetness [27].
• In the former we found that residual uninhibited activity remained in the presence of pHMB, in some cases accounting for up to 60% of the total reduction of cytochrome c. Thus, simply measuring the NADH-dependent reduction of cytochrome c consistently overestimated B5R activity [28].
• Separately, the inactivation of PON1 by p-hydroxymercuribenzoate (PHMB), a modifier of the cysteine residue, was also prevented by CLA isomers, suggesting the possible existence of the cysteine residue in the binding site of CLA [29].

Analytical, diagnostic and therapeutic context of p-Chloromercuribenzoic acid

• Amino acid analysis and titration with p-hydroxymercuribenzoate indicated that the 12 half-cystinyl residues present/subunit exist in the free sulfhydryl form [30].
• By using affinity gel chromatography, conversion of holo-CRABP into apo-CRABP by treatment with p-hydroxymercuribenzoate and a possible involvement of a thiol group in RA binding to CRABP were established [31].

References