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K H Kim

Publications and source records attributed to K H Kim.

At least 19 recordsLinked to original sources
PubMed1979

Control of acetyl-CoA carboxylase by covalent modification.

In this review, various experiments which establish the occurrence of covalent modification mechanisms, both in vivo and in vitro, in the control of acetyl-CoA carboxylase have been presented. It is interesting to note that phosphorylation of the carboxylase results in disaggregation of the active species. These studies indicate that aggregation and disaggregation of the enzyme are involved in the control of carboxylase activity. Our covalent modification mechanism and the allosteric control mechanism share a common ground in that both mechanisms affect the equilibrium between protomers and polymers of the enzyme. However, it is clear that the allosteric control mechanism cannot function alone under normal physiological conditions. Covalent modification of the carboxylase is prerequisite for efficient functioning of the allosteric mechanism. There are many aspects of the regulation of acetyl-CoA carboxylase which require further clarification. However, it is now established that short-term control of acetyl-CoA carboxylase involves the covalent modification mechanism.

Acetyl-CoA Carboxylase↗
PubMed1979

Isolation of estrogen receptor in complex with a discrete nuclear subfraction from hen oviduct.

A nuclear subfraction containing bound estrogen receptor in presumed complex with its nuclear acceptor site has been partially purified from hen oviduct. Sucrose density gradient ultracentrifugation was used to separate mechanically sheared chromatin (i.e. lysed nuclei) into several fractions which differed in protein to DNA ratio as well as in vitro template activity. Gradient fractions were then examined for the presence of bound estrogen receptors. Care was taken to use physiological ionic strength buffers when preparing nuclei since the number of estrogen receptors per nucleus decreased from 5600 to 1600 when nuclei prepared in low ionic strength (mu = 0.013 M) were compared with nuclei prepared in physiological ionic strength (mu = 0.2 M). [3H]Estradiol was introduced into nuclear estrogen receptors by exposing minced oviduct to labeled hormone in tissue culture or by exchanging nuclear estrogen receptor complexes formed in vivo with labeled hormone. In all cases, receptor was found in a fast sedimenting nuclear subfraction of low in vitro template activity. Sodium dodecyl sulfate-gel electrophoresis revealed no differences between proteins from receptor-containing and slower sedimenting fractions. Hybrdization experiments using a cDNA probe made from ovalbumin mRNA indicated no enrichment of this gene in DNA from receptor-containing nuclear material. Salt-extracted nuclear estrogen receptor was shown to partially aggregate to fast sedimenting species of heterogeneous size when sedimented in gradients containing low salt concentrations. Bound receptors were distinguished from such receptor aggregates using a novel electrophoresis technique. In addition, receptor aggregates could be disrupted in high salt, while bound receptors were resistant to this treatment. The number of exchangeable nuclear estrogen receptors in immature chicks given secondary estrogen stimulation was compared with birds that had been withdrawn from hormone. The number of receptors per nucleus was shown to be higher in animals given secondary stimulation, and these receptors were associated exclusively with fast sedimenting nuclear material.

Animals↗
PubMed1979

Stimulation by epinephrine of in vivo phosphorylation and inactivation of acetyl coenzyme A carboxylase of rat epididymal adipose tissue.

Intraperitoneal injection of inorganic 32P into rats results in the incorporation of 32P into acetyl-CoA carboxylase without inactivation of the enzyme. Administration of epinephrine stimulates 32P incorporation and results in enzyme inactivation. Incubation of epididymal fat tissues with inorganic 32P also results in incorporation of 32P into carboxylase. This 32P incorporation reaches a maximum level in 3 h and it has no effect on carboxylase activity. Administration of epinephrine at the time of maximum phosphorylation (3 h) results in further phosphorylation and inactivation of carboxylase. Propranolol, a beta-adrenergic blocking agent which inhibits epinephrine action, blocks both the epinephrine-stimulated phosphorylation and the inactivation of the carboxylase. However, propranolol has no effect on that component of the phosphorylation which is unrelated to enzyme inactivation. These results establish that phosphorylation of carboxylase occurs in vivo at two different sites, only one of which results in enzyme inactivation. The phosphorylation site associated with enzyme inactivation is hormonally controlled.

Acetyl-CoA Carboxylase↗
PubMed1979

Quantitative structure-activity relationships for biguanides, carbamimidates, and bisbiguanides as inhibitors of Streptococcus mutans No. 6715.

Thirty-seven compounds, including 17 biguanides, 6 carbamimidates, and 14 bisbiguanides, were evaluated for potential antiplaque activity by measuring their minimum inhibitory concentrations [MIC (M)] against Streptococcus mutans no. 6715. Linear regression analysis was conducted with the log 1/MIC (M) values and log P, pi, sigma, and MR. The best correlation for the biguanides (r2 = 0.92) was obtained with log P and (log P)2. When the biguanides were included with the carbamimidates, essentially the same correlation (r2 = 0.91) was obtained with log P and (log P)2. The best correlation for the bisbiguanides (r2 = 0.70) was also obtained with log P and (log P)2. Use of an indicator variable (I) for the bisgiguanides allowed all three groups to be included in one equation, which accounted for over 87% of the variance in the data for inhibition of bacterial growth. These results from the classical parabolic model were also compared with those from the recently developed bilinear model.

Biguanides↗
PubMed1979

Quantitative structure-activity relationships in 1-aryl-2-(alkylamino)ethanol antimalarials.

A quantitative structure-activity relationship has been formulated for 646 antimalarials acting against P. berghei in mice. The equation developed has 14 terms, 9 of which are indicator variables. The correlation coefficient for the QSAR is 0.898 and the standard deviation is 0.309. The antimalarials are all arylcarbinols of the type X-ArCHOHCH2NR1R2. Sixty different aryl structures, including a variety of heterocyles, are contained in the study. The most important determinate of activity is found to be the electron-withdrawing ability of the substituents X; the hydrophobic character of X and R plays less important roles. Suggestions for more potent analogues are made and the lack of activity of about 100 additional analogues is also considered.

Animals↗
PubMed1979

QSAR of alkyl pyridinecarbonyldithiocarbazates as uncouplers of oxidative phosphorylation.

The structure-activity relationship for alkyl dithiocarbazates and alkyl pyridinecarbonyldithiocarbazates as oncouplers of oxidative phosphorylation in rat liver mitochondria has been studied using subsituent constants and regression analysis. As in various other uncouplers, the hydrophobic property of substituents gave a good correlation with their biological activities. 4-Pyridinecarbonyldithiocarbazates are the most active among the congeners studied.

Animals↗
PubMed1978

Regulation of rat liver acetyl-CoA carboxylase. Stimulation of phosphorylation and subsequent inactivation of liver acetyl-CoA carboxylase by cyclic 3':5'-monophosphate and effect on the structure of the enzyme.

The effects of citrate and cyclic AMP on the rate and degree of phosphorylation and inactivation of rat liver acetyl-CoA carboxylase were examined. High citrate concentrations (10 to 20 mM), which are generally used to stabilize and activate the enzyme, inhibit phosphorylation and inactivation of carboxylase. At lower concentrations of citrate, the rate and degree of phosphorylation are increased. Furthermore, phosphorylation and enzyme inactivation are affected by cyclic AMP under these conditions. At high citrate concentrations, cyclic AMP has little or no effect on inactivation and phosphorylation of acetyl-CoA carboxylase. Phosphorlation and inactivation of carboxylase is accompanied by depolymerization of the polymeric form of the enzyme into intermediate and protomeric forms. Depolymerization of carboxylase requires the transfer of the gamma-phosphate group from ATP to carboxylase. Inactivation occurs in the absence of CO2, which indicates that phosphorylation of the enzyme is the cause of inactivation and depolymerization, i.e. carboxylation of the enzyme is not responsible for inactivation of the enzyme.

Acetyl-CoA Carboxylase↗
PubMed1978

Effect of epinephrine on acetyl-CoA carboxylase in rat epididymal fat tissue.

If acetyl-CoA carboxylase in epididymal fat tissue is subject to control by convalent modification as in the case of the liver enzyme, catalytically different forms of carboxylase should exist, independent of polymerization. By treating epididymal fat tissue in culture with epinephrine, we have demonstrated catalytically less active forms of acetyl-CoA carboxylase. The catalytically less active forms of the enzyme reacted to antibody with the same efficiency as the active form of carboxylase. However, the less active enzyme formed by epinephrine treatment of tissues has a sedimentation constant of 30 to 35 S, whereas that of the enzyme from control tissue is 45 S. Incubation of the less active forms of the carboxylase with 10 mM citrate and up to 10 mg/ml of bovine serum albumin activated the enzyme without any change in the sedimentation constant. Therefore, the less active forms of the carboxylase formed as a result of epinephrine treatment are not due to the depolymerization of polymeric forms (45 S) to the protomeric forms (17 to 20 S), but to the formation of intermediate species of carboxylase which cannot form polymeric enzyme (45 S) in the presence of high concentrations of citrate.

Acetyl-CoA Carboxylase↗
PubMed1977

Mechanism of palmityl coenzyme A inhibition of liver glycogen synthase.

Palmityl-CoA inhibits free liver glycogen synthase; the concentration required for half-maximum inhibition is 3 to 4 micrometer. Almost complete inhibition was observed at 50 micrometer. Palmityl-CoA inhibition is associated with dissociation of the tetrameric enzyme into monomers, and binding of palmityl-CoA to the monomers. Glycogen-bound enzyme is also inhibited by palmityl-CoA, resulting in dissociation of the enzyme into monomers and concomitant release of the enzyme from the primer glycogen. Palmityl-CoA inhibition of the enzyme is partially reversed by the glycogen synthase activator, glucose-6-P, whereas sodium lauryl sulfate-inhibited enzyme is not reactivated by glucose-6-P. Sodium lauryl sulfate inhibition results in the dissociation of the tetramer into the monomers. Bovine serum albumin and cyclodextrin can prevent palmityl-CoA inhibition only when they are added prior to palmityl-CoA addition. The possible physiological role of palmityl-CoA in glucose homeostasis is discussed.

Acyl Coenzyme A↗
PubMed1977

Quantitative structure-activity relationships for 5-substituted 8-hydroxyquinolines as inhibitors of dental plaque.

Fourteen 8-hydroxyquinolines were tested for antiplaque activity by measuring their minimum inhibitory concentrations [MIC (M)] against Streptococcus mutans No. 6715. Linear regression analysis was conducted with the MIC (M) values and hydrophobic (log P), electronic (beta, pKaOH, pKaN), and steric [molar refractivity (MR), molecular weight (mol wt)] parameters. The best correlation (r2 = 0.90) was obtained with MR, log P, and beta. The smaller the steric contribution of the 5-substituent, the more active the compound. The parent 8-hydroxyquinoline was the most active. The negative contribution toward activity by 5-substituents larger than hydrogen can be overcome by the positive contributions of groups that are lipophilic and electron withdrawing; for example, the 5-chloro derivative is as active as the parent 8-hydroxyquinolines.

Dental Plaque↗