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PubMed1975

Chemical modification of bovine heart mitochondrial malate dehydrogenase. Selective modification of cysteine and histidine.

Bovine mitochondrial malate dehydrogenase (EC 1.1.1.37) was inactivated by the specific modifications of a single histidine residue upon reaction with iodoacetamide. NADH protected against this loss of activity and reaction with the histidine residue, suggesting that the histidine is at the NADH binding site. N-Ethylmaleimide also modified the enzyme by reacting with 1 sulfhydryl residue. The reaction rate with N-ethylmaleimide was increased by decreasing the pH from neutrality or by the addition of urea. NADH protected against the modification of the sulfhydryl group under all the conditions tested, again suggesting active site specificity for this inactivation. This enzyme has a subunit weight of 33,000 and is a dimer. The native malate dehydrogenase will bind only 1 mol of NADH and it is thus assumed that there is only a single active site per dimer.

Amino Acids↗

PubMed1986

[Genetical aspects of hormonal modification of the stress reactivity. II. Modification in early ontogenesis of the stress reactivity of adult gray rats selected for behavior toward man].

Inherited and modificational changes of the stress reactivity in two outbreed stocks of wild Norway rats trapped in nature and selected for behaviour were studied. During 18 generations the rats of one stock were selected for the lack of defensive behaviour in the glove test (tame), while in another stock the aggressiveness was maintained by the selection (aggressive). Interstock differences in the brain noradrenaline mechanisms were observed. The emotional stress reactivity of the tame animals was decreased, in comparison with the aggressive ones. Definitive stress reactivity of adult rats was modified by injections of hydrocortisone to their mothers on the 16 and 18 days of gestation. Hormonal treatment changed noradrenaline mechanisms and decreased the reaction to emotional stressor in aggressive rats. The modified level of the stress reactivity of aggressive rats was similar to the definitive level of the tame ones. Hormonal treatment did not modify stress reactivity in tame rats. Thus, the phenotype only emerging in aggressive rats, as a result of hormonal modification, is the inherited norm of the tame animals. However, due to rat selection for the lack of defensive behaviour towards the man, high corticosteroid level in the blood of pregnant females, an external developmental factor, in respect to the fetus, loses regulatory function during the development of the neuroendocrine mechanisms of the stress reaction.

11-Hydroxycorticosteroids↗

PubMed1983

Cloning of the MspI modification enzyme. The site of modification and its effects on cleavage by MspI and HpaII.

The gene for the MspI modification enzyme from Moraxella was cloned in Escherichia coli using the plasmid vector pBR322. Selection of transformants carrying the gene was based on the resistance of the modified plasmid encoding the enzyme to cleavage by MspI. Both chromosomal and plasmid DNA were modified in the selected clones. None of the clones obtained produced the cognate restriction enzyme which suggests that in this system the genes for the restriction enzyme and methylase are not closely linked. Crude cell extracts prepared from the recombinant strains, but not the host (E. coli HB101), contain an S-adenosylmethionine-dependent methyltransferase specific for the MspI recognition site, CCGG. Production of the enzyme is 3-4-fold greater in the transformants than in the original Moraxella strain. 5-Methylcytosine was identified as the product of the reaction chromatographically. The outer cytosine of the recognition sequence, *CCGG, was shown to be the site of methylation by DNA-sequencing methods. This modification blocks cleavage by both MspI and its isoschizomer HpaII. HpaII, but not MspI, is able to cleave the unmethylated strand of a hemimethylated substrate. The relevance of these results to the use of MspI and HpaII to analyze patterns of methylation in genomic DNA is discussed.

Cloning, Molecular↗

PubMed1984

Modification and processing of Bacillus licheniformis prepenicillinase in Escherichia coli. Fate of mutant penicillinase lacking lipoprotein modification site.

We have previously shown that Bacillus licheniformis prepenicillinase is modified and processed to form membrane-bound penicillinase in Escherichia coli which contains N-acylglyceride-cysteine27 at the NH2 terminus. In the present study, we have constructed, by in vitro site-directed mutagenesis, two mutant penicillinase genes in which the modification site (the 27th cysteine residue in prepenicillinase) is either converted into serine (penPSer27) or is deleted along with the preceding four residues (Ala23 to Cys27, delta penP2327). The modification, processing, and subcellular localization of these two mutant penicillinases in E. coli cells were studied. Our results indicate that the delta penP2327 deletion mutant prepenicillinase is largely metabolically inert and the unmodified and uncleaved form is associated with the membrane fraction; a small fraction (about 7-9%) appears to contain glyceride-modified prepenicillinase (presumably at the Cys-21 position) which is not cleaved. In contrast, the Cys-27 in equilibrium Ser-27 point mutant prepenicillinase is processed into two forms which contain Asn-29 and Ser-35 at their NH2 termini, respectively, and the bulk of the processed penicillinase appears to be located in the peri-plasm. These results are discussed in terms of the substrate specificities of signal peptidases in E. coli.

Amino Acid Sequence↗

PubMed1976

Selective chemical modification of Escherichia coli elongation factor G. N-Ethylmaleimide modification of a cysteine essential for nucleotide binding.

Escherichia coli Elongation Factor G is inhibited ireversibly by the chemical modification of 1 cysteine residue with N-ethylmaleimide. At pH 5.2, this cysteine is approximately 130 times more reactive than beta-mercaptoethanol toward N-ethylmaleimide. Inhibition is not prevented by either the ribosome or GTP alone at concentrations approximately equal to that of Elongation Factor G, but in combination they reduce the inhibition by 50%. Increasing the stability of the Elongation Factor G-ribosome-GDP complex by the addition of fusidec acid, completely protects against N-ethylmaleimide inhibition. The modified protein cannot form either the Elongation Factor G-ribosome-GMP-P(CH2)P or the Elongation Factor G-ribosome-GDP-fusidic acidcomplex. However, the modification had no effect on its ability to form the Elongation Factor G-ribosome complex. These results suggest that the cysteine residue modified by N-ethylmaleimide is at or near the nucleotide binding site.

Binding Sites↗

PubMed1998

Molecular characterization of the Lactococcus lactis LlaKR2I restriction-modification system and effect of an IS982 element positioned between the restriction and modification genes.

The nucleotide sequence of the plasmid-encoded LlaKR2I restriction-modification (R-M) system of Lactococcus lactis subsp. lactis biovar diacetylactis KR2 was determined. This R-M system comprises divergently transcribed endonuclease (llaKR2IR) and methyltransferase (llaKR2IM) genes; located in the intergenic region is a copy of the insertion element IS982, whose putative transposase gene is codirectionally transcribed with llaKR2IM. The deduced sequence of the LlaKR2I endonuclease shared homology with the type II endonuclease Sau3AI and with the MutH mismatch repair protein, both of which recognize and cleave the sequence 5' GATC 3'. In addition, M. LlaKR2I displayed homology with the 5-methylcytosine methyltransferase family of proteins, exhibiting greatest identity with M. Sau3AI. Both of these proteins shared notable homology throughout their putative target recognition domains. Furthermore, subclones of the native parental lactococcal plasmid pKR223, which encode M. LlaKR2I, all remained undigested after treatment with Sau3AI despite the presence of multiple 5' GATC 3' sites. The combination of these data suggested that the specificity of the LlaKR2I R-M system was likely to be 5' GATC 3', with the cytosine residue being modified to 5-methylcytosine. The IS982 element located within the LlaKR2I R-M system contained at its extremities two 16-bp perfect inverted repeats flanked by two 7-bp direct repeats. A perfect extended promoter consensus, which represented the likely original promoter of the llaKR2IR gene, was shown to overlap the direct repeat sequence on the other side of IS982. Specific deletion of IS982 and one of these direct repeats via a PCR strategy indicated that the LlaKR2I R-M determinants do not rely on elements within IS982 for expression and that the efficiency of bacteriophage restriction was not impaired.

Amino Acid Sequence↗

PubMed1979

[Chemical modification of proteins. 5. Modification of the 11-S-globulin from sunflower seed by reaction with dialdehyde starch].

Dialdehyde starch (DAS) reacts unspecifically with the amino acid residues of the 11 S globulin from sunflower seed. The modification of the protein causes a decrease of the content of each amino acid. Their blocking reaches maximum values at high pH levels (9,5) and high concentration of protein (5%). Especially high reactivity is shown by arginine as well as by the hydrophobic amino acids isoleucine, valine, and proline, and furthermore by histidine, lysine, asparagine (aspartic acid), and glutamine (glutamic acid). By reaction with DAS at pH 8.0 70% of the amino groups are blocked within 6 h; on the contrary, glyoxale blocks only 30% of the amino groups. Owing to the blockage of charged amino acid groups, a shift of the isoelectric point of the protein to a lower pH (4,3-4,4) takes place; this effect can be followed for 2 days. As a result of the reaction with DAS, only small amounts (10-15%) of intermolecular crosslinkage products with sedimentation coefficients of 17 S and greater than 17 S were formed. But by means of SDS-gel electrophoresis, dimers and trimers of the polypeptide chains in the protein were detected.

Aldehydes↗

PubMedDate not supplied

Modification of polyetherurethane for biomedical application by radiation-induced grafting. I. Grafting procedure, determination of mechanical properties, and chemical modification of grafted films.

Radiation grafting of monomers onto suitable trunk polymers is a useful tool for tailoring new polymers for special purposes. This technique has been used in the past for the development of biocompatible materials, e.g., by grafting hydrogels onto mechanically stable polymers. In this first part of our work, the radiation grafting of hydrophilic or reactive monomers onto a polyetherurethane film using the pre-swelling technique is described. Following this technique the trunk polymer was swollen in the monomer before irradiation. As monomers 2-hydroxyethyl methacrylate (HEMA), 2,3-epoxypropyl methacrylate (GMA), 2,3-dihydroxypropyl methacrylate (GOMA), and acrylamide (AAm) were used. The kinetics of the grafting reactions were examined, and the distribution of the graft component inside the trunk polymer was investigated by means of infrared (IR) spectroscopy. Surface-grafted as well as bulk- and surface-grafted products could be obtained. The mechanical behavior of the grafted films--especially in the water-swollen state--was examined and compared with that of the pure trunk polymer. In nearly all cases it was found that the tensile strength sigma B and the elongation at break epsilon R decreases as the grafting yield increases. Modification of GMA- and AAm-grafted films via chemical reactions was performed to create new functional groups of biomedical interest. In this manner a diol structure, a carboxylic acid structure, and a sulfonic acid group could be introduced in the grafted polymer. The water uptake of such modified films is increased markedly when compared with that of the unmodified samples.

Biocompatible Materials↗

PubMed1980

Restriction and modification in Bacillus subtilis: identification of a gene in the temperate phage SP beta coding for a BsuR specific modification methyltransferase.

A gene coding for a modifying DNA-methyltransferase which methylates the central C in the BsuR recognition sequence 5'GGCC was identified in the genome of the temperature Bacillus subtilis phage SP beta. This gene is expressed only after induction of the prophage by either mitomycin C or UV. The presence of active methyltransferase in induced cells leads to modification of BsuR recognition sites in SP beta DNA as well as in heterologous DNA.

Bacillus subtilis↗

PubMed1996

Prevalence of hypertension in 1,795 subjects with chronic renal disease: the modification of diet in renal disease study baseline cohort. Modification of Diet in Renal Disease Study Group.

The Modification of Diet in Renal Disease Study was a multicenter trial of the effect of protein restriction and strict blood pressure control on the progression rate of chronic renal failure of multiple causes. At the first baseline visit, 1,795 screened patients with renal disease had blood pressure measured, antihypertensive medications recorded, glomerular filtration rate (GFR) determined by 125I-iothalamate clearance, a nutritional assessment, and a 24-hour urine collection to determine sodium and potassium levels. A total of 1,494 patients in this cohort were classified as hypertensive (83%) and the remainder (301 patients) as nonhypertensive. Ninety-one percent of the hypertensive subjects were on treatment, 54% being controlled to a blood pressure of < or = 140/90 mm Hg. To better understand the factors that contribute to the development of hypertension in chronic renal disease, some determinants of the prevalence of hypertension in this cohort were investigated. Compared with normotensive subjects, hypertensive patients were older (51.2 +/- 12.7 years v 46.6 +/- 13.1 years [mean +/- SD]), had a higher body mass index (BMI; 27.5 +/- 4.7 kg/m2 v 25.4 +/- 4.2 kg/m2), and had a lower GFR (37.8 +/- 19.6 mL/min/1.73 m2 v 50.1 +/- 25 mL/min/1.73 m2). All these differences were significant (P < 0.01). The prevalence of hypertension was significantly higher for men than for women (86% v 80%; P = 0.001), and for blacks than for whites (93% v 81%; P < 0.001). The prevalence of hypertension was higher in subjects with glomerular disease than in those with tubulointerstitial disease (85% v 62.6%; P < 0.001). The prevalence of hypertension varied inversely with GFR (from 66% at a GFR of 83 mL/min/1.73 m2 to 95% at a GFR of 12 mL/min/1.73 m2). The prevalence of hypertension varied directly with BMI (from 70% with a BMI at the 10th percentile to 94% with a BMI at the 97th percentile). This relationship was independent of GFR. Multiple logistic regression analysis showed five predictors in decreasing order of significance as determined by chi-square values: GFR, 83.2; BMI, 36.7; black race, 19.9; increasing age, 14.5 (all P < 0.001); and male gender, 5.1 (P = 0.024). Salt intake was not a determinant of blood pressure status. These results confirm previous reports indicating that hypertension in renal disease is determined by the level of renal function. For the first time, three factors known to predict blood pressure levels in populations with normal renal function were also shown to be determinants of blood pressure in renal disease: BMI, black race, and age. In addition, the data suggest that hypertension is inadequately treated in more than half of patients with chronic renal disease in the United States.

Adolescent↗

PubMed1994

Investigation of ionizable residues critical for sequence-specific enzymatic DNA modification: protein modification and steady-state and pre-steady-state kinetic pH analyses of EcoRI DNA methyltransferase.

Steady-and pre-steady-state pH kinetic analyses are widely used methods to investigate important ionizable groups in enzyme-catalyzed reactions. The first such analysis to identify ionizable residues critical for sequence-specific modification of DNA is presented. EcoRI DNA methyltransferase uses S-adenosyl-L-methionine (AdoMet) to catalyze the N6 methylation of the second adenine in the double-stranded DNA sequence GAATTC. The kinetic mechanism was previously shown to be steady-state-ordered bi bi in which AdoMet binds first followed by DNA addition [Reich, N. O., & Mashhoon, N. (1991) Biochemistry 30, 2933-2939]. Steady-state parameters are strongly dependent on pH and implicate at least four residues with pKa values between 8.2 and 8.9 in the free enzyme and AdoMet-Bound enzyme and one residue with an apparent pKa of 6.0. The data obtained are consistent with the enzyme binding the form of AdoMet in which the alpha amino group is protonated. Two protein residues with an apparent pKa between 8.9 and 9.2 were implicated within the central complex (enzyme-DNA-AdoMet). The general insensitivity of all steady-state parameters to pH changes between pH 6.0 and 8.0 suggests that no critical protein residues undergo ionization-state changes in this range. The lack of significant pH-dependent changes in protein fluorescence and DNA thermal stability suggests minimal structural changes in either macromolecule. In support of the steady-state results single-turnover experiments reveal minimal pH dependence of the methylation rate constant between pH 5.53 and 8.6. Thus, no amino acids critical for catalysis undergo ionization-state changes in this range.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

PubMed1988

UV-induced vanadate-dependent modification and cleavage of skeletal myosin subfragment 1 heavy chain. 1. Evidence for active site modification.

Ultraviolet irradiation above 300 nm of the stable MgADP-orthovanadate (Vi)-myosin subfragment 1 (S1) complex resulted in covalent modification of the S1 and in the rapid release of trapped MgADP and Vi. This photomodified S1 had Ca2+ATPase activity 4-5-fold higher than that of the non-irradiated control S1, while the K+EDTA-ATPase activity was below 10% of controls. There was a linear correlation between the activation of the Ca2+ATPase and the release of both ADP and Vi with irradiation time. Analysis of the total number of thiols and the ability of photomodified S1 to retrap MgADP by cross-linking SH1 and SH2 with various bifunctional thiol reagents indicated that the photomodification did not involve these reactive thiols. Irradiation of the S1-MgADP-Vi complex caused a large increase in absorbance of the enzyme at 270 nm which was correlated with the release of Vi from the active site, suggesting an aromatic amino acid(s) was (were) involved. However, analysis by three different methods showed no loss of tryptophan. All the irradiation-dependent phenomena could be prevented by replacing Mg2+ with either Co2+, Mn2+, or Ni2+. Unlike previous irradiation studies of Vi-dynein complexes [Lee-Eiford, A., Ow, R. A., & Gibbons, I. R. (1986) J. Biol. Chem. 261, 2337-2342], no peptide bonds were cleaved in photomodified S1. Photomodified S1 was able to retrap MgADP-Vi at levels similar to unmodified S1. Upon irradiation of the photomodified S1-MgADP-Vi complex, MgADP and Vi were again released from the active site, resulting in heavy chain cleavage to form NH2-terminal 21-kDa and COOH-terminal 74-kDa peptides. All evidence indicates that this new photomodification and subsequent chain cleavage occur specifically at the active site.

Adenosine Diphosphate↗

PubMed1992

C-terminal modifications of nonpeptide renin inhibitors: improved oral bioavailability via modification of physicochemical properties.

We describe the development of a series of soluble, potent, and bioavailable nonpeptide renin inhibitors. These inhibitors derived from a series of novel nonpeptide renin inhibitors which were recently identified in our laboratories, by alteration of the nature of the C-terminus (P2') of the molecules. Introduction of basic substituents into modified hydroxyethylene dipeptide isosteres gave inhibitors with improved solubility as well as improved potency against human plasma renin. In addition, these modifications produced inhibitors which displayed markedly improved intraduodenal bioavailability in both the ferret and cynomolgus monkey. We also present data which demonstrate excellent efficacy in the monkey for A-74273 (65), with an intraduodenal bioavailability of 16 +/- 4% in the monkey, compared to 1.7 +/- 0.5% for the dipeptide renin inhibitor enalkiren (A-64662, 75). A-74273 is an example of a nonpeptide inhibitor which possesses a good balance of the desirable properties of potency, solubility, and lipophilicity and which is well absorbed into the intestine.

Administration, Oral↗

PubMed1990

Chemical modification of pig liver initiation factor eIF-2 with N-ethylmaleimide. Amino acid sequences around the N-ethylmaleimide-reactive sulfhydryl groups and the effect of GDP on the modification.

The activity of eukaryotic initiation factor eIF-2 as to the formation of the ternary complex, eIF-2 GTP Met-tRNA(f), is inhibited by N-ethylmaleimide. Our preparation of pig liver eIF-2 contained alpha and gamma subunits and was inhibited by more than 90% by N-ethylmaleimide. Using our eIF-2, we determined the sequences around the N-ethylmaleimide-reactive sulfhydryl groups, studied the effect of GDP on the sulfhydryl modification and that of NEM on the [3H]GDP binding, and examined the protective effect of GTP against the inhibition of ternary complex formation by N-ethylmaleimide. Both subunits of native eIF-2 contained [14C]N-ethylmaleimide-reactive sulfhydryl groups. One N-ethylmaleimide-reactive sulfhydryl group was in the alpha subunit and 4 were in the gamma subunit. The sequence of the peptide of the alpha subunit was determined to be: Ala-Gly-Leu-Asn-Cys-Ser-Thr-Glu-Thr-Met-Pro-Ile. Two of the four [14C]N-ethylmaleimide-reactive sulfhydryl groups in the gamma subunit were highly reactive, their sequences being: Ile-Val-Leu-Thr-Asn-Pro-Val-Cys-Thr-Glu-Val-Gly-Glu-Lys (gamma 1); Ser-Cys-Gly-Ser-Ser-Thr-Pro-Asp-Glu-Phe-Pro-Thr-Asp-Ile-Pro-Gly-Thr-Lys (gamma 3a). Peptide gamma 3a contained the consensus sequence element (AspXaaXaaGly) of GTP-binding proteins. With preincubation of eIF-2 with GDP, the incorporation of [14C]N-ethylmaleimide into the gamma subunit was reduced to 40% of the control level, but the 14C-incorporation into the alpha subunit did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1987

Highly controlled carbodiimide reaction for the modification of lysozyme. Modification of Leu129 or Asp119.

In the cross-linking reaction of lysozyme between Leu129 (alpha-COO-) and Lys13 (epsilon-NH3+) using imidazole and 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide hydrochloride (EDC), a side reaction of the peptide bond inversion from alpha to beta between Asp101 and Gly102 was greatly reduced by addition of beta-(1,4)-linked trimer of N-acetyl-D-glucosamine [(NAG)3]. When methylamine or 2-hydroxyethylamine was further added, the extent of the cross-link formation was decreased and the derivative where the alpha-carboxyl group of Leu129 was modified with the amine was newly obtained. On the other hand, when ammonia was added, the beta-carboxyl group of Asp119 instead of the alpha-carboxyl group was mainly amidated. From these results, the presence of a salt bridge between Asp119 and Arg125 besides that between Lys13 and Leu129, is proposed. Enzymatic activities of the derivatives prepared here indicated that the modification of the alpha-carboxyl group reduced the activity to approximately 90% of that of native lysozyme. Des-Leu129 lysozyme, which lacks Leu129, also showed approximately 90% of the activity of native lysozyme. Therefore, the salt bridge between Lys13 and Leu129 may play some role in maintaining the active conformation of lysozyme.

Amino Acid Sequence↗

PubMed1996

Peroxynitrite modification of glutathione reductase: modeling studies and kinetic evidence suggest the modification of tyrosines at the glutathione disulfide binding site.

The catalytic properties of glutathione reductase for its substrate, glutathione disulfide, were altered following a 60 s exposure to a 100-fold molar excess of peroxynitrite; the K(M) value was increased by approximately 2.5-fold and the V(max) value was decreased by approximately 1.7-fold. The kinetic alterations are thought to result from nitrotyrosine formation as the intrinsic Tyr fluorescence is diminished. The UV-visible spectrum of glutathione reductase exhibited absorbance at approximately 423 nm, characteristic of nitrotyrosine. In addition, the presence of nitrotyrosine has been detected by Western immunoblots with an anti-nitrotyrosine antibody. The peroxynitrite-induced inactivation is not observed in the presence of excess glutathione disulfide. However, excess NADPH offered no protection against peroxynitrite-induced inactivation. These observations suggest that the modification of approximately 1.8 Tyr per subunit, at or near the glutathione disulfide binding domain, probably results in the observed catalytic alterations. To test this hypothesis, the two tyrosines closest to the glutathione disulfide binding domain (Tyr114 and Tyr106), as indicated by the X-ray crystallographic data [Karplus and Schulz (1989) J. Biol. Chem., 210, 163-180], were each converted to nitrotyrosines by molecular modeling and the structure energy was minimized. These theoretical calculations indicate that the bond lengths between Tyr114-O and the Gly-N and Cys II-N of glutathione disulfide bound to glutathione reductase (Karplus and Schulz, 1989) increased by 3.0 and 4.3 A, respectively, upon nitration. In the case of Tyr106 the 0-Cys II-N distance also increases by approximately 1.6 A. The loss of these hydrogen bonding contacts is likely to result in the observed catalytic alterations upon reaction with peroxynitrite.

Animals↗

PubMed1990

Inactivation of bacteriophage T7 DNA-dependent RNA polymerase by 5'-p-fluorosulfonylbenzoyladenosine. Identification of the modification site and the effect of the modification on enzyme action.

Bacteriophage T7 RNA polymerase was covalently modified by 5'-[4-fluorosulfonyl)benzoyl]adenosine (4-FSO2BzAdo). The modified enzyme lacks the ability to catalyze RNA synthesis from the phi 10 promoter of bacteriophage T7; both promoter and GTP binding being markedly decreased. The mild hydrolysis of the ester bond of 4-FSO2BzAdo within the covalent enzyme-inhibitor complex restores the RNA synthesis at a lower rate. Sequence studies show that Lys172 is the target of modification by 4-FSO2BzAdo. This residue, which is situated in the polypeptide region connecting two domains of RNA polymerase, was shown to be the primary site of the limited proteolysis occurring in vivo [Ikeda, R. A. & Richardson, C. C. (1987) J. Biol. Chem. 262, 3790-3799]. We propose that Lys172 is located outside the active site. Once this residue has reacted with 4-FSO2BzAdo, the nucleoside moiety of the analog is fixed in the NTP-binding site of the active centre and prevents binding of the substrates. Here, Lys172 per se is not important for the activity but serves as an 'anchor' for binding of the inhibitor.

Adenosine↗

PubMed1990

Covalent modification and metabolic control analysis. Modification to the theorems and their application to metabolic systems containing covalently modifiable enzymes.

A study of the sensitivity properties of metabolic systems containing covalently modifiable enzymes and cascades has been carried out with the aid of metabolic control analysis. We have considered how the theorems of metabolic control analysis must be modified to take into account covalently modifiable enzymes, and have used these results to investigate the effects of increasing the total amount of modifiable enzyme. The sensitivity of system variables to an effector acting through a covalent-modification cycle has also been investigated.

Energy Metabolism↗