PubMed Health⌕ Search

Biomedical subjects

M I Mackness

Publications and source records attributed to M I Mackness.

At least 91 records · Page 5Linked to original sources
PubMed1991

Serum paraoxonase activity in familial hypercholesterolaemia and insulin-dependent diabetes mellitus.

The activity of serum paraoxonase, an enzyme located on high-density lipoprotein, has been investigated in familial hypercholesterolaemia (FH) and insulin dependent diabetes mellitus (IDDM). Increases in total serum cholesterol and apolipoprotein B were present in both FH and IDDM compared to healthy controls and in the patients with IDDM, serum triglycerides were also raised. The serum HDL-cholesterol concentrations in controls and patients with FH and IDDM did not differ significantly. Serum paraoxonase activity was significantly lower in both the FH and IDDM populations than in controls (P less than 0.001 and P less than 0.01, respectively). 72% of the FH population and 67% of the IDDM population were in the lower half of the frequency distribution for serum paraoxonase (activity of less than 112 U/l). It is likely that the common factor related to low paraoxonase activity is hyperlipidaemia. It is possible that paraoxonase has a physiological role in lipid metabolism and that decreases in its activity may accelerate atherogenesis.

Apolipoproteins B↗
PubMed1990

Serum esterase activities and hyperlipidaemia in the streptozotocin-diabetic rat.

The levels of activity of four serum esterases were measured in control and streptozotocin-diabetic rats for a period of 6 months. Pseudocholinesterase activity was significantly elevated in the diabetic rats at all time points tested, reaching 250% of the control activity at 6 months. Levels of paraoxonase activity progressively decreased with time in the diabetic rats, being 36% lower than in controls at 6 months. No significant differences in either serum arylesterase or carboxylesterase activity between control and diabetic rats were observed.

Animals↗
PubMed1989

Absence of "A"-esterase activity in the serum of a patient with Tangier disease.

The levels of apolipoprotein A-I, A-II and B in subjects who are homozygous or heterozygous for Tangier disease are reported and compared with the amount of "A"-esterase in the serum. The "A"-esterases hydrolyse toxic organophosphate pesticides and are currently classified by the nomenclature committee of the International Union of Biochemistry as arylesterases (EC 3.1.1.2) although recent evidence has cast doubt on this classification. The apolipoprotein data are consistent with previous data reported for a number of Tangier patients. The homozygote has a marked reduction in apo A-I and A-II levels and a 30% reduction in apo B. The heterozygotes have about a 50% reduction of apo A-I, a slight reduction in apo A-II and no change in apo B. These apolipoprotein values correspond to a marked reduction in HDL cholesterol for the homozygote and substantial reductions in the heterozygotes. The "A"-esterase activity is zero in one homozygote while heterozygotes have about 5% of the levels in control subjects. Arylesterase activity appears to be essentially normal. The data thus support previous observations that the HDL "A"-esterase activity is greatly reduced in those conditions where HDL apo A-I is markedly reduced, e.g., in "Fish-eye" Disease.

Apolipoprotein A-I↗
PubMed1988

Multiple forms of sheep serum A-esterase activity associated with the high-density lipoprotein.

Five lipoproteins of sheep serum expressing A-esterase activity, but with differing activities towards four organophosphate substrates, were separated by a combination of gel filtration and ion-exchange chromatography. Each had an Mr of approx. 360,000 and contained a major peptide of Mr 28,000-30,000 that appeared to be present as several isoforms on urea/agarose isoelectric focusing. In every case this peptide split into a number of bands on urea/agarose isoelectric focusing. The bands appear to represent isoforms of the peptide, and four lipoproteins yielded characteristic patterns of bands. This peptide resembles the apolipoprotein A-I of human serum, and available evidence suggests that this is the protein that expresses A-esterase activity. Evidence is presented for the existence of different species of high-density lipoprotein HDL2 particles containing different complements of peptide isoforms and expressing contrasting substrate specificities towards organophosphates.

Animals↗
PubMed1987

Distinction between 'A'-esterases and arylesterases. Implications for esterase classification.

'A'-esterase activities (substrates paraoxon and pirimiphos-methyloxon) and arylesterase activities (substrate phenyl acetate) were assayed in the sera of 14 species of birds representing seven different orders and 11 species of mammal representing five different orders. Ten species of birds had no detectable 'A'-esterase, and the remaining four species only low activity, yet all birds showed considerable arylesterase activity (16.8-99.3 mumol/min per ml of serum). Ten species of mammal showed both 'A'- and 'aryl'-esterase activities. In humans, gel filtration of serum completely separated peaks representing paraoxonase and arylesterase activities. Thus, in both birds and humans, serum enzymes exist that express arylesterase activity but not 'A'-esterase activity. These findings suggest that a distinction should be made between these two types of esterase in future classifications.

Animals↗
PubMed1987

Peroxisomal localization of glucose-6-phosphate dehydrogenase and pyrophosphate-stimulated dihydroxyacetone-phosphate acyltransferase in mouse kidney.

1. The subcellular localization of dihydroxyacetone-phosphate acyltransferase (DHAPAT) (assayed in the presence of pyrophosphate) and glucose-6-phosphate dehydrogenase (NADP+-dependent) activity in mouse kidney was investigated by density-gradient centrifugation. 2. DHAPAT has a predominantly peroxisomal distribution, and the activity in purified peroxisomes is stimulated by various organic and inorganic phosphate-containing compounds. The pH optimum is acid. 3. Approx. 10% of the cellular NADP+-dependent glucose-6-phosphate dehydrogenase activity is associated with peroxisomal fractions and may provide a source of NADPH for the peroxisomal reduction of acyl-dihydroxyacetone phosphate formed by DHAPAT activity.

Acyltransferases↗
PubMed1987

"A" esterases and their role in regulating the toxicity of organophosphates.

Esterases which can hydrolyse organophosphates without being inhibited by them are termed "A" esterases. Using paraoxon and pirimiphos-methyl oxon as substrates, high "A" esterase activity is found in the liver and plasma or serum of a range of mammalian species. In a study of serum "A" esterases of sheep and humans, over 80% of the activity separated into the high density lipoprotein (HDL) fraction following ultracentrifugation. When HDL fractions from sheep serum were run on Sepharose gel columns, most of the paraoxonase activity separated as a single peak of estimated molecular weight 360,000, which corresponds to that of HDL2 of humans. During the course of purification of "A" esterases by three different column procedures, contrasting esterase elution profiles were obtained with organophosphate and pyrethroid substrates. This was strong evidence for the existence of multiple forms of HDL "A" esterases. Levels of "A" esterase activity in plasma and liver of birds were much lower than those of mammals. This appears to be the main reason why birds are much more susceptible than mammals to organophosphates such as pirimiphos-methyl and diazinon which form active oxons that are good substrates for mammalian "A" esterases. No "A" esterase was detected in strains of rust red flour beetle (Tribolium castaneum) which were resistant to organophosphates. Similar observations have been made with strains of other insects resistant to organophosphates, raising the question to what extent esterases of this type are present in insects.

Animals↗
PubMed1987

Low A-esterase activity in serum of patients with fish-eye disease.

The activity of HDL-associated paraoxonase in the lipoprotein fraction of serum from two patients with fish-eye disease (FED) was only 11% of the mean value for control subjects. Similarly, concentrations of apolipoproteins A-I and A-II in the serum of FED subjects were only 10% of those in normal subjects. Thus the ratio of enzyme activity to A-I and A-II is virtually the same in these two groups of subjects. This suggests that paraoxonase activity of the lipoprotein fraction is associated with one or both of these apolipoproteins.

Apolipoprotein A-I↗
PubMed1986

Subcellular localization of epoxide hydrolase in mouse liver and kidney.

The subcellular distribution of epoxide hydrolase activity towards TSO and HEOM in mouse liver and kidney was investigated using zonal rotor centrifugation. Epoxide hydrolase activity towards TSO was found predominantly in the soluble fraction with peroxisomes accounting for activity in the particulate fractions. Renal particulate activity towards HEOM was found predominantly in the microsomes.

Animals↗
PubMed1986

Distribution of paraoxon hydrolytic activity in the serum of patients after myocardial infarction.

The activity of paraoxonase in serum was found to be bimodally distributed, both in a control group and in a group of patients who had suffered myocardial infarction. Activity in the myocardial infarct group was significantly lower than in the control group. Low paraoxonase activity in serum may provide an indication of susceptibility to the development of coronary heart disease.

Aryldialkylphosphatase↗
PubMed1985

Predominant localization of dihydroxyacetone-phosphate acyltransferase activity in renal peroxisomes of male and female mice.

The subcellular localization of DHAPAT activity in male and female albino mouse kidneys was investigated by density gradient centrifugation. DHAPAT has a predominantly peroxisomal distribution in both male and female kidneys; however some activity is also distributed in a less dense region of the gradient, predominantly containing microsomes. Peroxisomal fractions also contain some lactate dehydrogenase activity and approximately 9% of the cellular NAD-dependent alpha-glycerophosphate dehydrogenase activity.

Acyltransferases↗
PubMed1985

The separation of sheep and human serum "A"-esterase activity into the lipoprotein fraction by ultracentrifugation.

Using sheep and human serum the relationship between centrifugation time and yield of total lipoprotein, HDL-cholesterol and "A"-esterase in lipoprotein was studied employing different centrifuge rotors. More rapid separation of these components was obtained with a vertical rotor than with an angled rotor. The procedures commonly employed for lipoprotein separation gave low yields of lipoprotein "A"-esterase and HDL-cholesterol. The separation of sheep serum "A"-esterase into the lipoprotein fraction was not in phase with that of HDL-cholesterol and the pattern of separation was different from that in human serum. These results provide further evidence that serum "A"-esterase activity is associated with different species of HDL-particle.

Animals↗