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Biomedical subjects

J Hajdu

Publications and source records attributed to J Hajdu.

At least 109 records · Page 6Linked to original sources
PubMed1982

Synthesis of enzyme-inhibitory phospholipid analogs. III. A facile synthesis of N-acylaminoethylphosphorylcholines.

A facile and efficient synthesis of N-aceylaminoethylphosphorylcholines, a series of inhibitory substrate analogs of phospholipase A2, is described. The procedure consists of a three-step sequence including: (1) N-acylation of ethanolamine with fatty acid chloride, followed by (2) phosphorylation of the alcohol function using 2-chloro-2-oxo-1,3,2-dioxaphospholane and (3) nucleophilic ring opening of the cyclic phosphate triester (IV) with anhydrous trimethylamine. The resulting isosteric amide analogs of glycol-lecithins have been isolated in high yields. The synthesis is illustrated by the preparation of the compounds containing palmitoyl, stearoyl and lauroyl fatty acid side-chains. The N-acylaminoethylphosphorylcholines have been shown to function as reversible phospholipase A2 inhibitors. They are likely to become a new series of useful substrate analogs and an attractive replacement for the n-alkylphosphorylcholines commonly used as single-chain-carrying phospholipase inhibitors.

Chemical Phenomena↗
PubMed1982

Interaction of ligands in phosphorylase A as monitored by crosslinking and enzymatic modifications: synergism of glucose and caffeine manifested in the exposure of N-terminal segment.

1. Glycogen, caffeine and glucose dissociate phosphorylase a tetramer to dimers with half-maximum effect at 0.16%, 1.1 and 71 mM concentration, respectively, as monitored by crosslinking with dimethyl suberimidate at 18 degrees C. 2. The above ligands increase the rate of dephosphorylation and tryptic digestion of phosphorylase alpha at 18 degrees C in the same way with half-maximum effect at 0.04%, 0.1 and 9 mM concentration, respectively. 3. Caffeine and glucose acted synergistically in tetramer dissociation as well as in the enzymic modifications. 4. The alpha-anomer of D-glucose was twice as effective as its mutarotational equilibrium solution.

Animals↗
PubMed1982

Structural features of platelet activating factor (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) required for hypotensive and platelet serotonin responses.

A number of analogs similar in structure to biologically active 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet activating factor) were tested for their relative effectiveness in lowering the blood pressure of spontaneous hypertensive rats and in releasing [3H]serotonin from rabbit platelets. Except for some minor variations, the two test systems gave the same pattern of relative responses for a given analog. Both biological activities (the antihypertensive response and release of platelet serotonin) appear to be stereospecific since the unnatural isomer exhibited no detectable effects. Other structural modifications that greatly reduced (greater than 500-fold) or eliminated the two biological activities were: 1) removal of the acetate group, 2) substitution of the acetate group with long-chain acyl, methoxy, benzoxy, N-formyl, N-trifluoroacetyl, N-hexadecanoyl, or deoxy groups such as dimethyl, propyl, isopropyl, or isobutyl, and 3) replacement of the sn-1 0-alkyl group with an acyl moiety. Biological activities were reduced to a lesser extent (100- to 500-fold) when the sn-2 carbon contained butyrate or hexanoate groups or if ethanolamine was substituted for the choline base. Replacing the sn-2 acetate group with an ethoxy group lowered the activity 48- and 120-fold for the blood pressure and serotonin release, respectively. Substitution of propionate for acetate at the sn-2 carbon gave a compound that was at least, if not more, biologically active than the parent structure; although an N-acetyl analog possessed biologic activities, the responses were only 0.27 to 1.0% of those obtained with the O-acetyl lipid. Maximum biological activity for both hypotensive effects and platelet serotonin release required a glycerolipid having an alkyl ether at the sn-1, acetate or propionate groups at the sn-2, and phosphocholine at the sn-3 positions.

Animals↗
PubMed1981

Kinetic behaviour and oligomeric state of 3-phosphoglyceroyl-D-glyceraldehyde-3-phosphate dehydrogenase.

The specific activity of pig muscle D-glyceraldehyde-3-phosphate dehydrogenase was found to be constant in the reverse reaction, with NADH and 1,3-diphosphoglycerate as substrates, over the enzyme concentration range 10(-8) to 10(-4) M. The molecular weight of the covalent intermediate of the enzyme, 3-phosphoglyceroyl-glyceraldehyde-3-phosphate dehydrogenase, as measured by sedimentation techniques, proved constant (145 000 +/- 6 000) between 3 x 10(-5) M enzyme concentration. Likewise, no change in the apparent molecular weight was observed by gel-chromatography even at 2 x 10(-8) M enzyme concentration. The data indicate that the enzyme functions in its tetrameric form.

Animals↗
PubMed1981

HLA haplotypes in children with adrenogenital syndrome and their parents.

HLA-A and B antigen typing was carried out by the standard NIH lymphocytotoxicity test in children with adrenogenital syndrome (AGS) from 11 families, further in 3 healthy siblings and 20 obligatory gene carrier parents. Of the children 7 had the salt-losing form. The AGS homozygote group was examined for the geno- and haplotypes of the HLA antigen and the heterozygote group for HLA antigen genotypes. Two AGS-affected children of the same family proved to be HLA-identical, while in other families the haplotypes of the healthy siblings were different from those of the affected children. As compared with the data of 222 healthy blood donors, the antigens of the HLA-A and B loci in the homo- and heterozygote groups showed no significant difference.

Adrenal Hyperplasia, Congenital↗
PubMed1980

Structural changes in glycogen phosphorylase as revealed by cross-linking with bifunctional diimidates: phospho-dephospho hybrid and phosphorylase a.

The technique of cross-linking with a series of bifunctional diimidates (maximal effective length ranging from 3.7 to 14.5 A), followed by dodecyl sulfate gel electrophoresis, was applied to compare the subunit contact areas of phosphorylases b, ab (the phospho-dephospho hybrid), and a and to study the structure and ligand-induced structural changes in phosphorylases ab and a. Similarly to phosphorylase b, the nearest cross-linkable lysyl-NH2 groups are about 3.7 A apart across the intradimer subunit interface (contact m) and about 8 A apart across the interdimer interface (contact d) in both phosphorylases ab and a. The activation of phosphorylase b induced by phosphorylation and that elicited by AMP binding are distinguishable at both contacts m and d. Phosphorylases ab and a tend to form tetramers whose structures are not identical, but AMP renders phosphorylase ab similar to phosphorylase a. Glucose, caffeine, and glycogen are able to dissociate both a and ab tetramers to dimers, whereas glucose 6-phosphate can only dissociate phosphorylase ab. The structure around the nucleotide site of phosphorylase a is rigid so that ligands binding here, such as AMP, ATP, ADP, inosine monophosphate, and glucose 6-phosphate, fail to influence the cross-link pattern. In control, in phosphorylase ab contact m is markedly affected by AMP, ATP, and glucose 1-phosphate; hence, in this respect phosphorylase ab resembles phosphorylase b.

Adenine Nucleotides↗
PubMed1979

Amidination of amino groups of aldehyde reductase from human liver.

Amidination of human liver aldehyde reductase (alcohol:NADP+ oxidoreductase, EC 1.1.1.2) with monofunctional n-alkane methylimidates increased the enzymic activity by 10--30%, whereas analogous bifunctional imidoesters caused a loss of activity of about 80%. Both effects were prevented in the presence of the coenzyme NADPH or NADP+, but not of the substrate 4-nitrobenzaldehyde. Amidination increased the apparent Michaelis constant of both the coenzyme (up to 20-fold) and the substrate (about 5-fold). Bifunctional imidoesters with at least 4 carbon atoms between the functional groups (approx. 0.7 nm) crosslinked the enzyme intramolecularly. This reaction was retarded in the presence of the coenzyme, whereas 4-nitrobenzaldehyde had no effect. The results suggest the presence of reactive amino groups at the coenzyme binding site of aldehyde reductase.

Alcohol Oxidoreductases↗
PubMed1979

Molecular forms of purified human erythrocyte membrane acetylcholinesterase investigated by crosslinking with diimidates.

Several molecular forms of human erythrocyte membrane acetylcholinesterase have been studied after crosslinking with bifunctional diimidates. The crosslinked products were analysed by centrifugation on linear sucrose density gradients containing Triton X-100. Molecular weights of covalently linked oligomers were estimated by sodium dodecylsulfate gel electrophoresis. It was shown that acetylcholinesterase crosslinked in absence of Triton X-100 consists of molecular forms built up by dimeric protomers. These dimers were identical with the enzymatically active species sedimenting with 6.5S in linear sucrose density gradients.

Acetylcholinesterase↗
PubMed1977

Properties of human erythrocyte catalases after crosslinking with bifunctional reagents. Symmetry of the quaternary structure.

Normal erythrocyte catalase, the enzyme present in the blood of Swiss acatalasemic heterozygotes, and their hybrid produced in vitro, were studied after crosslinking with bifunctional reagents. On theoretical grounds [cf. Hajdu, J., Bartha, F. & Friedrich, P. (1976) Eur. J. Biochem. 68, 373--383] it is inferred from the dodecylsulphate gel electrophoretic patterns obtained after treating catalase with diimidates of various chain lengths that the enzyme is an isologous tetramer (D2 symmetry). The minimal distances between crosslinkable primary amino groups across the three domains of bonding are different. Reaction with diimidates causes a moderate loss of enzyme activity in all three enzyme types due to amidination rather than crosslink formation. On the other hand, crosslinking stabilizes the enzyme against urea and heat inactivation. This is most prominent with heterozygote acatalasemic catalase. Crosslinking markedly prevents the development of peroxidase activity that can be elicited in catalases by urea treatment. The role of the quaternary structure of the protein in the relationship between catalase and peroxidase activities is discussed.

Animals↗
PubMed1976

Crosslinking with bifunctional reagents as a means for studying the symmetry of oligomeric proteins.

A method based upon the principle that unlike domains of bonding are reflected in different reactivities and distribution of residues that can be crosslinked, has been elaborated for the determination of symmetry of oligomeric proteins. The derivation of theoretical curves for the prediction of crosslinking patterns of tetramers produced by reaction with a bifunctional reagent and subsequent sodium-dodecylsulphage-gel electrophoretic analysis, is presented. Based upon the theory the symmetry properties of a tetramer, to the extent whether it is an isologous or heterologous association, can be deduced by a simple calculation. Crosslinking patterns obtained with rabbit muscle aldolase and pig muscle lactate dehydrogenase after treatment with a series of diimidoesters of increasing chain length are evaluated and shown to be consistent with the expectations for isologous tetramers. From the patterns obtained with the various reagents the distances between lysyl residues located nearest to each other in different subunits in the two proteins could also be determined.

Actins↗