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Biomedical subjects

R J Pollitt

Publications and source records attributed to R J Pollitt.

At least 109 records · Page 6Linked to original sources
PubMed1980

The use of arginine analogues for investigating the functional organization of the arginine-binding site in lobster muscle arginine kinase. Role of the 'essential' thiol group.

1. The nature of arginine binding to lobster arginine kinase and the extent of its possible involvement with the ;essential' thiol group of the enzyme has been investigated with some inhibitory analogues of arginine. 2. Most of the analogues inhibit competitively, although mixed inhibition may occur if the alpha-carboxy group or alpha-amino group is absent. 3. The K(i) values indicate that strength of binding depends on the length of the carbon chain (l-isoleucine>l-valine>l- alpha-aminobutyrate>l-alanine) and the integrity of the substituents on the alpha-carbon atom (l-arginine>agmatine and l-ornithine>putrescine). The guanidino group probably contributes little to substrate binding, but a positive charge near the delta-nitrogen atom appears to be important (l-ornithine>l -citrulline>l-alpha-aminobutyrate). A cyclic analogue, 2-carboxymethyl-3-oxo-2,3,5,6,7,8-hexahydro-1H-imidazo [1,2-a][1,3]diazepine-8-carboxylic acid, has a low K(i) value similar to that of an equivalent straight-chain form, suggesting that arginine probably binds in a folded configuration. 4. The aliphatic l-amino acids give enzyme difference spectra similar to that with l-arginine and the integrity of the alpha-carboxy and alpha-amino groups appears to be a minimal but not sufficient requirement for this, as l-ornithine gives an atypical difference spectrum. A difference spectrum is interpreted as indicating an enzyme conformational change. No difference spectrum was observed with methylguanidine. 5. The ability of aliphatic alpha-l-amino acids to protect against inhibition by 5,5'-dithiobis-(2-nitrobenzoic acid) is proportional to the number of atoms in the carbon chain and inversely proportional to K(i). Ornithine gives greater protection than citrulline; analogues lacking the alpha-amino groups also protect. Agmatine, lacking the alpha-carboxy group, did not protect. 6. It is concluded that it is unlikely that the ;essential' thiol group in the enzyme interacts with any part of the arginine molecule during catalysis except, possibly, the alpha-carboxyl group.

Animals↗
PubMed1980

Alpha-aminoadipic aciduria: chemical and enzymatic studies.

A new case of alpha-aminoadipic aciduria had an apparent immunodeficiency and died at the age of 4 months. The urine contained large amounts of alpha-aminoadipate and smaller quantities of alpha-keto- and alpha-hydroxyadipate. Post mortem, the highest concentrations of alpha-aminoadipate were found in liver and kidney. Enzymatic studies on liver and cultured fibroblasts failed to demonstrate the expected deficiency of alpha-amino-adipate aminotransferase, a result perhaps explicable by the presence of cytoplasmic aminotransferase activity.

2-Aminoadipic Acid↗
PubMed1980

Ascorbic acid: an unstable ninhydrin-positive urinary constituent running with valine in a commonly used screening system.

Large amounts of ascorbic acid occur occasionally in the urine of children being investigated for possible inherited metabolic disease and may give a positive ninhydrin reaction after thin-layer chromatography. As this compound is unstable in urine and runs with valine in a solvent system commonly used for preliminary screening, it is a possible source of confusion.

Ascorbic Acid↗
PubMed1979

The occurrence of gamma-glutamylphenylalanine in the urine of newborn phenylketonurics.

The urine of untreated phenylketonurics in the first weeks of life contains gamma-glutamylphenylalanine (0.07--0.69 mmol/g creatinine, 12 samples) visible on the normal 2-dimensional electrophoreto-chromatogram. This compound is less prominent or absent when urine from older untreated phenylketonurics is examined and is not seen in normal urine.

Creatinine↗
PubMed1979

Urinary dicarboxylic acids in patients receiving lithium or rubidium salts.

Lithium salts administered in therapeutic doses to four subjects who were kept on controlled diets increased up to fivefold the urinary output of some dicarboxylic acids. Some of the acids affected are intermediates in the tricarboxylic acid cycle, others are chemically similar but not directly related in metabolic terms. This is probably a direct effect on renal transport. Rubidium salts increased urinary 2-oxoglutarate output and blood 2-oxoglutarate levels, probably by some action on intermediary metabolism.

Bipolar Disorder↗
PubMed1978

3-Aminopiperid-2-one, an unusual metabolite in the urine of a patient with hyperammonaemia, hyperornithinaemia and homocitrullinuria.

The urine of a patient with a disorder characterized by hyperammonaemia, hyperornithinaemia and homocitrullinuria contains abnormal amounts of 3-aminopiperid-2-one. The properties of this compound closely resemble those ascribed previously (Gordon, B.A., Gatfield, P.D. and Taller, E. (1977) Clin. Biochem. 10, 78-82) to ornithine methyl ester. The excretion of the aminopiperidone ranged from 130-1050 micronmol/g creatinine.

Amino Acid Metabolism, Inborn Errors↗
PubMed1978

The labelling of urinary acids after oral doses of deuterated L-phenylalanine and L-tyrosine in normal subjects. Quantitative studies with implications for the deuterated phenylalanine load test in phenylketonuria.

Oral doses of L-[2H5]-phenylalanine (25 mg/kg) and L-[2H2]-tyrosine (12.5 mg/kg) were given separately to three normal subjects and together to a fourth. Blood samples were analysed for deuterium labelled phenylalanine and tyrosine, and urine for labelled o-and p-hydroxyphenylacetic, p-hydroxyphenyllactic and p-hydroxymandelic acids. The labelling patterns of the urinary metabolites indicated that the para-compounds all originated in both hepatic and extra-hepatic tissues. The plasma tyrosine did not appear to be in equilibrium with the tyrosine in the liver. It is concluded that a simple quantitative relationship between the labelling of these metabolites and the synthesis of labelled tyrosine from labelled phenylalanine in liver is unlikely.

Acids↗
PubMed1977

Carbamyl-phosphate-synthetase deficiency with neonatal onset of symptoms.

The clinical course and biochemical findings in a case of carbamyl-phosphate-synthetase deficiency are described. The patient, a boy, presented 48 h after birth with rapidly developing hypotonia and hypothermia. Pulmonary haemorrhage, melaena and haematemesis ensued and despite ventilatory assistance and peritoneal dialysis the patient died on the fifth day. A virtual absence of carbamyl phosphate synthetase I (N-acetylglutamate dependent) was proved by analysis of tissue samples removed post mortem. Other urea cycle enzymes were normal.

Amino Acids↗
PubMed1976

Ornithine transcarbamylase deficiency: enzyme studies on a further case and a method of diagnosis using plasma enzyme ratios.

The activities of the urea cycle enzymes in the liver of a female patient with hyperammonemia were determined (Table 1). Ornithine transcarbamylase (OTC, EC. 2.1.3.3) was reduced to 5-10% of normal and the residual enzyme showed an apparent Kmorn of 0.69 (normal 0.37 +/- 0.10) mmol liter. The pH dependence was normal. The patient's mother also showed hyperammonemia but was not clinically affected. Consideration of the genetics of the disease suggested that many female patients should have a mixture of normal and mutant enzymes. Electrophoresis of the patient's liver extract showed an additional band of OTC activity probably due to this mutant enzyme. The ratio of plasma glutamate-pyruvate transaminase to OTC was abnormal in four clinically affected patients with OTC deficiency (Fig. 4B) but not in two of their mothers without clinical signs.

Alanine Transaminase↗
PubMed1976

[Attempt at antenatal diagnosis of argininosuccinic aciduria].

Antenatal diagnosis in a woman previously delivered of a child with arginino-succinic aciduria, due to deficiency of arginino-succinase (EC 4.3.2.1.), showed the fetus to be unaffected. This was confirmed at birth.

Amino Acid Metabolism, Inborn Errors↗