B. Halpern

The urinary organic acid profile associated with 3-hydroxy-3-methylglutaric aciduria

Abstract The urinary organic acid profile of 3-hydroxy-3-methylglutaric aciduria contains excessive amounts of 3-methylglutaconic acid, 3-hydroxy-3-methylglutaric acid, 3-hydroxyisovaleric acid and 3-methylglutaric acid. The previously reported 3-methylcrotonic acid was shown to be an artefact and is not a diagnostic metabolite for this defect.

Quantitative determination of biologically important thiols and disulfides by gas-liquid chromatography.

Abstract Aminothiols and disulfides react rapidly with pivaldehyde (2,2-dimethylpropanal) at room temperature and at a neutral pH to form volatile neopentylidine derivatives suitable for gas-liquid chromatography. The derivatives from cysteamine, cystamine, cysteine, S-methylcysteine, cystine, homocysteine, homocysteine thiolactone, homocystine, methionine, penicillamine, and cysteaminecysteine mixed disulfide can be separated in 15 minutes on an SE-30 column. The method may be used to determine the nonprotein bound thiols and disulfides in biological materials.

Chlorination studies. I - The reaction of aqueous hypochlorous acid with cytosine.

Abstract Cytosine, 5-chloro- and 5-methylcytosine react with one equivalent of HOCl to yield the corresponding 4-N-chloro derivatives (II, VIII and IX). Two or three equivalents of HOCl with cytosine yield mixtures of II and VIII accompanied by two unstable compounds identified as a di- and tri-chlorocytosine respectively. Five equivalents of HOCl when reacted with cytosine produce unstable tri- and tetrachloro-derivatives. Acidification of II with dilute HCl, HBr or HI affords 5-Cl, 5-Br and 5-iodocytosine respectively. An aqueous suspension of II partially converts phenylalanine into phenylacetaldehyde.

The mass spectrometric identification of dipeptides in the urine of a patient suffering from chronic skin ulceration and oedema.

The identification of a complex ninhydrin positive mixture present in the urine of a child suffering from chronic skin ulceration and oedema by direct chemical ionisation mass spectrometric analysis is described. The compounds were shown to be dipeptides, of which glycylproline was the major constituent. At least 15 dipeptides were identified in the urine, most of which contained proline or hydroxyproline in the carboxy terminal position. The results suggested that the patient suffered from a defect in collagen metabolism. This hypothesis was subsequently confirmed by a grossly diminished level of prolidase in cultured fibroblasts and erythrocytes.

The Use of R-(+)-1-Phenylethylisocyanate in the Optical Analysis of Asymmetric Secondary Alcohols by Gas Chromatography

Abstract Gas chromatography of diastereoisomeric carbamates has been used to determine the steric purity of asymmetric alcohols. The relative retention times of the diastereoisomers could be used to assign the absolute configuration of a homologous series of secondary alcohols.

Chlorination studies. IV1. The reaction of aqueous hypochlorous acid with pyrimidine and purine bases

Abstract The labile intermediates and stable end products formed by the reaction of aqueous HOCl with thymine, uracil, 5-Br-uracil, N,N-dimethyluracil and 6-methyluracil have been identified. The purine ring system of guanine, adenine and xanthine was more resistant to attack by aqueous HOCl and reaction times of one week resulted in the formation of parabanic acid. Caffeine and theophylline under similar reaction conditions yielded N,N-dimethylparabanic acid.

Dicarboxylic aciduria: The response to fasting

The urine of a child who presented with an episode of a disease resembling Reyes syndrome was found to contain large quantities of the dicarboxylic acids adipic and suberic acids, as well as the glycine conjugate of suberic acid, suberyl glycine. A variety of other dicarboxylic acids, both saturated and unsaturated, were also found in the urine at the time of the attack. It was found that the excretion of these unusual metabolites could be markedly increased by fasting for periods of greater than 10 h. These results indicate that the patient may have a defect in fatty acid oxidation which becomes clinically significant during periods of prolonged fasting.

New metabolites in isovaleric acidemia.

Two metabolites, 4-hydroxyisovaleric acid and mesaconic acid, have been identified and quantified in the urine of a patient with isovaleric acidemia. These compounds do not appear to have been reported previously as being components of human metabolism. In addition, large quantities of 3-methylbutyrolactone, the lactone of 4-hydroxyisovaleric acid, were observed in the volatile profile obtained by headspace chromatography. The demonstration of 4-hydroxyisovaleric acid supports the contention that urinary methylsuccinic acid seen in patients with isovaleric acidemia has arisen by omega-oxidation of isovaleric acid. The identification of mesaconic acid may indicate that the methylsuccinic acid formed in these patients is subject to further metabolism.

Search for Organic Compounds in the Lunar Dust from the Sea of Tranquiblity

A sample of lunar dust was examined for organic compounds. Carbon detected in concentrations of 157 micrograms per gram had a δ13C per mil (PDB) value of + 20. Treatment with hydrochloric acid yielded hydrocarbons of low molecular weight, suggesting the presence of carbides. The gas chromatogram of the acylated and esterified derivatives of the hydrolyzate was similar to that obtained for the Pueblito de Allende meteorite. There were no detectable amounts of extractable high-molecular-weight alkanes, aromatic hydrocarbons, isoprenoid hydrocarbons, normal alkanes, fatty acids, amino acids, sugars, or nucleic acid bases. Traces of porphyrins were found, perhaps arising from rocket exhaust materials.

ISOLATION AND IDENTIFICATION OF γ-AMINOBUTYRYL-CYSTATHIONINE FROM HUMAN BRAIN AND CSF

Abstract— A new dipeptide, γ‐aminobutyryl‐cystathionine, has been identified in human brain and CSF. The compound was isolated from peptide concentrates which were prepared by removing free a‐amino acids from deproteinized brain extracts on a copper Sephadex column. The isolated peptide was shown to be GABA‐Cysta by standard chemical methods, and its identification was confirmed by mass spectrometry. GABA‐Cysta is present in both biopsy and autopsy specimens of adult human brain, its content in some brain areas being as high as 0.090 μrnol/g wet weight. Its concentration in CSF is much lower. What physiologic role this unusual peptide plays in brain remains to be determined.