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Biomedical subjects

O A Mamer

Publications and source records attributed to O A Mamer.

At least 55 records · Page 3Linked to original sources
PubMed1988

Interference of 3-hydroxyisobutyrate with measurements of ketone body concentration and isotopic enrichment by gas chromatography-mass spectrometry.

Concentrations and 13C2 molar percentage enrichments of blood R-3-hydroxybutyrate and acetoacetate are measured by selected ion monitoring gas chromatography-mass spectrometry. Samples are treated with NaB2H4 to reduce unlabeled and labeled acetoacetate to corresponding deuterium-labeled RS-3-hydroxybutyrate species. Only the gas chromatographic peak for the tert-butyldimethylsilyl derivative of 3-hydroxybutyrate needs to be monitored. The various compounds are quantitated using an internal standard of RS-3-hydroxy-[2,2,3,4,4,4-2H6]-butyrate. Concentrations of ketone bodies are obtained by monitoring the m/z 159 to 163 fragments of tert-butyldimethylsilyl derivatives of labeled and unlabeled 3-hydroxybutyrate species. High correlations were obtained between ketone body concentrations assayed (i) enzymatically with R-3-hydroxybutyrate dehydrogenase and (ii) by gas chromatography-mass spectrometry. The limit of detection is about 10 nmol of substrate in blood samples. The current practice of monitoring the m/z 275 to 281 fragments overestimates the concentration of endogenous R-3-hydroxybutyrate, due to co-elution of 3-hydroxyisobutyrate, a valine metabolite. The method presented is used to measure ketone body turnover in vivo in 24-h-fasted dogs.

3-Hydroxybutyric Acid↗
PubMed1988

Measurement of urinary lactic, 3-hydroxybutyric, pyruvic and acetoacetic acids in a single analysis using selected ion monitoring and stable isotope labelling techniques.

Sodium borodeuteride treatment of urine expected to have large concentrations of pyruvic and acetoacetic acids produces lactic and 3-hydroxybutyric acids labelled with deuterium. Mass fragmentographic techniques applied to the trimethylsilyated extract of the urine spiked with more extensively labelled analogues as internal standards permit the reliable determination of lactic, pyruvic, 3-hydroxybutyric and acetoacetic acids in a single analysis.

3-Hydroxybutyric Acid↗
PubMed1986

Stable isotope dilution assay for branched chain alpha-hydroxy-and alpha-ketoacids: serum concentrations for normal children.

A stable isotope dilution assay is described for the six branched chain alpha-hydroxyacids and alpha-ketoacids that accumulate in serum in maple syrup urine disease. The method employs sodium borodeuteride reduction of the alpha-ketoacids in situ to once-labeled hydroxyacids, addition of a more extensively labeled analog as internal standard, isolation of the organic acids by ether extraction, and quantitation by gas chromatography/mass spectrometry in selected ion monitoring mode. A set of three areas are obtained for each of the three branched chain hydroxyacid peaks, and these are corrected for natural abundance heavy isotope content and for isotopic impurities in the labeled standards and precursors. The corrected areas are then converted to concentrations of the endogenous three hydroxyacids and the original three ketoacids in serum.

Child↗
PubMed1985

Identification of urinary 3-ethoxy-4-hydroxybenzoic and 3-ethoxy-4-hydroxymandelic acids after dietary intake of ethyl vanillin.

It has been discovered recently that several patients undergoing urinary organic acid profiling excrete high concentrations of 3-ethoxy-4-hydroxybenzoic acid and traces of 3-ethoxy-4-hydroxymandelic acid. These are believed to be the consequences of feeding the patients with synthetic diets flavoured with 3-ethoxy-4-hydroxybenzaldehyde, a vanilla-like artificial flavouring added to improve patient acceptance and taste. The syntheses, mass spectra and gas chromatographic behaviour of these and related compounds are presented.

Adult↗
PubMed1985

In vitro metabolism of 25-hydroxycholecalciferol by isolated cells from human decidua.

An increase in maternal serum levels of 1 alpha, 25-dihydroxycalciferol during pregnancy has been linked to enhancement of intestinal calcium absorption. Several sites of its synthesis have been proposed in different species, human decidua being one of them. Collagenase-dispersed decidual cells isolated from term placenta were fractionated on a Percoll gradient. The isolated cells were set in culture in the presence of 6 nM [3H]cholecalciferol. Two cell populations of similar morphology hydroxylated the substrate, yielding a compound that had a mass spectrum identical to and that comigrated with authentic 1 alpha, 25-dihydroxycholecalciferol in four chromatographic systems and bound to a specific rachitic chick receptor. These preparations, thus, provide a potential system by which the kinetics and regulation of the synthesis of the hormonal form of vitamin D by human placenta can be studied in vitro.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1984

Determination of plasma bupropion and its relationship to therapeutic effect.

An analytical method to determine the concentration of bupropion in human plasma has been developed using a deuterium-labeled analog as internal standard and selected ion monitoring applied to an extract of plasma samples taken as part of a clinical trial of this antidepressant. In all, 15 depressed outpatients were randomly assigned to bupropion in a double-blind study which included weekly evaluation of their clinical condition. A good correlation was found between the results obtained by this assay and by a radioimmunoassay technique currently in use. While no simple correlation between plasma concentration and therapeutic improvement was noted, the majority of subjects showed mild to marked amelioration of symptoms and those having mean concentrations above 35 ng ml-1 had significant improvement in their test scores. Interpretation of the mass spectra of both the labeled and unlabeled drug revealed an apparent violation of the 'even-electron rule'.

Amitriptyline↗
PubMed1983

Apparent gastrointestinal origin of cis-4-hydroxycyclohexanecarboxylic acid.

We identified by gas chromatography-mass spectrometry the unusual substance cis-4-hydroxycyclohexanecarboxylic acid (4-HCH) in the urine of a child. Urinary excretion of 4-HCH and intestinal bacteria were both suppressed by neomycin treatment. We propose that 4-HCH is a by-product of bacterial metabolism.

Bacteria↗
PubMed1983

Metabolism of ethylmalonate to mesaconate in the rat. Evidence for trans-dehydrogenation of methylsuccinate.

Rats excrete increased ethylmalonate and methylsuccinate when given ethylmalonate in the diet; when given methylsuccinate they excrete methylsuccinate and mesaconate. Tenfold more labelled mesaconate was produced from threo-methyl[2,3-2H2] succinate precursor than from the erythro isomer. Our findings suggest trans-dehydrogenation of methylsuccinate and are the first direct evidence linking the metabolism of ethylmalonate, methylsuccinate and mesaconate.

Animals↗
PubMed1983

Metabolism of methylmalonic acid in rats. Is methylmalonyl-coenzyme a racemase deficiency symptomatic in man?

Vitamin B12-deficient and normal rats were loaded with methylmalonic (MMA) and ethylmalonic acids labeled with 13C in the carboxyl groups and with 2H in the alkyl groups. Significant fractions of the administered acids were excreted in both the B12-deficient and the normal animal, having undergone exchange of both their 13C-labeled carboxyl groups with endogenous 12C. The exchange of the alpha-1H of MMA in 2H2O at 25 degrees C and pH 7.5 was found by 1H-nuclear magnetic resonance to have a half-life of 28.3 min. These results show that a fraction of in vivo metabolism through the propionate-to-succinate pathway occurs via a shunt involving free MMA. The enzymes of this pathway are thought to utilize only coenzyme A (CoA) esters. To allow for the exchange of the second CoA-bound carboxyl group, we propose the deacylation of the once exchanged acid with spontaneous racemization (relative to the 13C-carboxyl group), followed by reacylation, thus exposing the labeled carboxyl to decarboxylation. The significance of this mechanism involving free MMA is that racemization of methylmalonyl (MM)-CoA may also occur without the intervention of MM-CoA racemase. A deficiency of this enzyme need not result in symptomatic methylmalonic aciduria.

Animals↗
PubMed1983

Episodic hypoglycemia with psi-hydroxy fatty acid excretion.

We present case histories of two young children with episodes of hypoglycemia, elevation of SGOT, low insulin levels, increased urinary excretion of psi-hydroxy fatty acids (5-hydroxyhexanoic, 7-hydroxyoctanoic and 9-hydroxydecanoic), traces of the corresponding psi-ketoacids and elevations of urinary adipic, suberic, and sebacic acids. The ratio of psi-hydroxy fatty acids to 3-hydroxybutyric in the urine of these patients is higher than in patients of similar ages with similar illnesses. These acids persisted while the patients were well. Increased urinary psi-hydroxy fatty acids could be reproduced by a load of medium chain triglycerides without precipitating other clinical symptoms. Three children with hypoglycemia were found not to excrete measurable amounts of these unusual acids while ill. A medium chain triglyceride load in one of these children after recovery failed to elicit psi-hydroxy acid excretion. Small amounts of urinary 5-hydroxyhexanoic acid only were found in two patients with acute Reye's syndrome and in three of five severely ill children with starvation ketonuria. In this last group, no urinary psi-hydroxyacids could be detected after recovery. Normal children do not excrete measurable amounts (less than 1 mg/g creatinine) of these psi-hydroxyacids.

Aspartate Aminotransferases↗
PubMed1980

Profiles in altered metabolism. II--(omega -- 1)-hydroxyacid excretion in a case of episodic hypoglycemia.

A patient with recurrent severe hypoglycemia resembling Reye's syndrome was found to have large accumulations of omega -- 1 hydroxy and keto acids in serum and urine that persisted following clinical recovery. A deficiency of mitochondrial medium chain acyl CoA dehydrogenase activity is proposed on the basis of evidence obtained using gas chromatographic mass spectrometric techniques. Analytical data is presented that will allow the recognition of ths variant presenting in other patients.

Acute Disease↗
PubMed1980

Hydroxymethylglutaryl CoA lyase deficiency: features resembling Reye syndrome.

A 2-year-old boy had acute fever, malaise, and somnolence with hepatomegaly, increased blood ammonia content (338 microM), high SGOT, low blood glucose content, and mild acidosis. A liver biopsy showed diffuse accumulation of lipid droplets in swollen hepatocytes, and abnormal urinary metabolites included beta-hydroxy-beta-methyl glutarate (HMG), beta-methylglutaconate, beta-hydroxyisovalerate, and beta-methylglutaric and glutaric acids. In cultured skin fibroblasts and liver, beta-hydroxy-beta-methyl glutaryl CoA lyase activity was about 10% of normal. Therefore, a genetic deficiency of HMGCoA lyase activity can cause a clinical syndrome similar to that of Reye syndrome when the patient is stressed by an acute viral infection.

Amino Acids↗
PubMed1979

Acetoacetyl CoA thiolase deficiency: a cause of severe ketoacidosis in infancy simulating salicylism.

A female child presented at one year of age with a febrile illness and loose stools, then developed severe ketoacidosis with vomiting; an apparent salicylate level of 11 mg/dl was measured. A sibling had died in similar circumstances nine years earlier. Investigation revealed that the child did not have salicylate intoxication, and that high levels of acetoacetate in blood and urine were giving readings indicative of the presence of salicylate on routine testing. Gas-liquid chromatographic analysis combined with mass spectrometry on urine samples revealed the presence of 2-methyl-acetoacetate, 2-methyl-3-hydroxybutyrate, and tiglyl glycine in appreciable amounts, indicating a defect in isoleucine catabolism located at the beta-ketothiolase step. The oxidation of 14C-isoleucine to CO2 in cultured fibroblasts confirmed that this pathway was defective. We present evidence that beta-ketothiolase deficiency is not simply a defect of isoleucine degradation; the deficient enzyme is the K+ dependent short-chain mitochondrial thiolase, which also plays a major catalytic role in ketone body and fatty acid oxidation.

Acetoacetates↗
PubMed1978

Profiles in altered metabolism I--the organic acids accumulating in acute non-diabetic ketoacidosis associated with alcoholism.

Several organic acids, among them the acidic catabolites of the branched chain amino acids and tyrosine, have been found to be elevated in the sera of non-diabetic patients presenting acute ketoacidosis associated with alcohol abuse. These findings are interpreted in terms of insufficiency of dietary co-factors required for their further catabolism. Butane-2,3-diol is also found frequently elevated in the urine of these patients and suggests interception of hydroxyethyl thiamine pyrophosphate by circulating high levels of acetaldehyde.

Acidosis↗