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Biomedical subjects

H C Curtius

Publications and source records attributed to H C Curtius.

At least 73 records · Page 4Linked to original sources
PubMed1980

A new rearrangement reaction in tyrosine metabolism.

Human faecal specimens were incubated under anaerobic conditions with several dideuterated tyrosine metabolites. 3-(4-Hydroxy[3,5-2H2]phenyl)propionic acid and 3-(4-hydroxy[3,5-2H2]phenyl)lactic acid yielded the rearrangment product 3-(3-hydroxy[2,4-2H2]phenyl)propionic acid. The starting materials as well as the product all contained two deuterium atoms both ortho to the hydroxyl group. Therefore the rearrangement reaction must depend on a shift of the side chain.

Chemical Phenomena↗
PubMed1980

Excretion of pterins in phenylketonuria and phenylketonuria variants.

Total urinary biopterin (B), neopterin (Ne) and monapterin (M) were measured in 25 healthy newborns, children and adults, in 49 patients with phenylketonuria (PKU) assumed to be deficient in phenylalanine-4-hydroxylase (PH), in 7 patients with dihydrobiopterin synthetase (DHBS) deficiency and in 4 patients with dihydropteridine reductase (DHPR) deficiency. Excretion of Ne based on creatinine (Ne/C) was 6.6 times higher in healthy newborns than in adults, suggesting a slow maturation of DHBS activity. Newborns excreted more Ne than B and adults more B than Ne (32 and 72% B of the sum of B + Ne, respectively). In all cases, excretion of M was 4-15% of that of Ne. PH deficient patients excreted more B and Ne than healthy controls and again, newborns more than older children. In individual patients, excretion of pterins correlated with phenylalanine (Phe) concentration in plasma; plasma Phe of different patients did not correlate well with excretion of pterins. In PKU variants with deficiency of tetrahydrobiopterin (BH4), extreme pterin patterns were observed: in DHBS- and DHPR-deficient patients, less than 3.5 and more than 81% B were found, respectively. All 30 samples from these patients investigated could be distinguished from those of PH-deficient patients and controls by a two-dimensional plot of % B versus B/C. Thus it seems likely that PKU variants due to BH4 deficiency could be detected early and differentiated by measurement of urinary B, Ne and C. This was exemplified already in one case. - In urine of patients with DHBS deficiency, high concentrations of 3'-hydroxysepiapterin were found in addition to Ne.

Adolescent↗
PubMed1979

Atypical phenylketonuria caused by 7, 8-dihydrobiopterin synthetase deficiency.

A patient with atypical phenylketonuria and normal liver dihydropteridine reductase and phenylalanine-4-hydroxylase activities excreted neopterin but not biopterin or dihydrobiopterin in urine. The oral administration of L-sepiapterin (1 mg/kg body weight) lowered serum-henylalanine from 17.1 to 1.1 mg/dl within 6 h. Comparable responses were observed after oral administration of L-erythro-7, 8-dihydrobiopterin or L-erythro-5, 6, 7, 8-tetrahydrobiopterin (each given in a dose of 2.5 mg/kg body weight). The results indicate a 7, 8-dihydrobiopterin synthetase deficiency in the patient.

Alcohol Oxidoreductases↗
PubMed1979

["Transitory" phenylketonuria. A permanent deficit].

Three cases are reported with hyperphenylalaninaemia greater than 1.8 micrometer/ml-1 in the neonatal period, becoming tolerant of a normal regime (3 g protein per kg) without plasma levels of phenylalanine exceeding 0.2 to 0.3 micrometer/ml-1. Atypical kinetics (zero order) of phenylalanine clearance after intravenous perfusion were shown in the three cases at the age of one year and the persistence of the disorder was again demonstrated at the age of five years in two cases by the study of an oral load of phenylalanine. Examination of the parents showed normal fasting levels of phenylalanine and a normal phenylalanine/tyrosine ratio. The observations draw together several previous publications from diverse authors and a new defined entity, "transitory" phenylketonuria, is proposed. It does not always appear to be a homogenous condition, as a partial defect in biopterin synthesis has been shown in the one case. In retrospect no anomaly of this kind was discovered in the other two cases where the mechanism was not elucidated.

Biopterins↗
PubMed1979

Nutritive value of N-acetyl-L-tryptophan in man.

The nutritive value of N-acetyl-L-tryptophan was investigated by loading tests with deuterated L-tryptophan and deuterated N-acetyl-L-tryptophan in three healthy adults, and by a 7 day-long feeding experiment with deuterated N-acetyl-L-tryptophan in one healthy adult. After loading with deuterated N-acetyl-L-tryptophan, serum levels of deuterated tryptophan and kynurenine were only about 10%, and the amounts of deuterated 5-hydroxyindole-3-acetic acid excreted in 24 h approximately 30% of those found after deuterated tryptophan loading. During the feeding experiment with deuterated N-acetyl-L-tryptophan, the serum level of deuterated tryptophan remained below 20% of total serum tryptophan, and serum protein fell below the normal range. It is concluded that the nutritive value of N-acetyl-L-tryptophan is inferior to that of L-tryptophan. Contradictory findings of earlier studies are discussed.

Blood Proteins↗
PubMed1978

Selective ion monitoring of tryptophan, N-acetyltryptophan and kynurenine in human serum. Application to the in vivo measurement of tryptophan pyrrolase activity.

A specific method is described for the determination of deuterated and non-deuterated N-acetyltryptophan, tryptophan and kynurenine in human serum and urine using gas chromatography-mass fragmentography. N-Acetyltryptophan was analysed as the N-trimethylsilyl methyl ester derivative; tryptophan and kynurenine were converted into their N-pentafluoropropionyl methyl esters. N-Acetyl-DL-tryptophan-d11, tryptophan-d8 and kynurenine-d2 were used as internal standards. The coefficients of variation were found to be about 8% (n = 9) for tryptophan and N-acetyltryptophan and about 2.4% (n = 9) for kynurenine. Using this method, an in vivo determination of the tryptophan pyrrolase activity [L-tryptophan oxygen 2,3-oxidoreductase (decyclizing), E.C. 1.13.11.11] is possible by loading the subjects with deuterated L-tryptophan-d5 and subsequently measuring the deuterated L-kynurenine-d4 formed and the residual L-tryptophan-d5.

Acetylation↗
PubMed1978

Tetrahydrobiopterin therapy of atypical phenylketonuria due to defective dihydrobiopterin biosynthesis.

A patient with atypical phenylketonuria (defective BH2 synthesis), detected at age 6 months because of severe muscle hypotonia and serum phenylalanine of 20 mg/100 ml, had normal activities of phenylalanine-4-hydroxylase and DHPR in liver biopsy, but only 2% activity in the phenylalanine-4-hyroxylase in vivo test using deuterated phenylalanine. After IV administration of 2.5 mg/kg chemically pure tetrahydrobiopterin bishydrochloride (BH4 . 2HCl), serum phenylalanine decreased from 20.4 to 2.1 mg/100 ml within 3 hours. Administration of 25 mg BH4 . HCl and 100 mg ascorbic acid through a gastric tube decrease; serum phenylalanine from 13.7 to less than 1.6 mg/100 ml within 3 hours and it remained less than 2 mg/100 ml for 2 days.

Biopterins↗
PubMed1978

In vivo studies of the phenylalanine-4-hydroxylase system in hyperphenylalaninemics and phenylketonurics.

An in vivo determination of the phenylalanine-4-hydroxylase (E. C. 1.14.16.1) activity is described. Subjects were loaded wit deuterated L-phenylalanine-d5 (200 mg/kg), and the deuterated tyrosine and deuterated phenylalanine in plasma was analyzed using mass fragmentography. Six phenylketonurics (PKU), four hyperphenylalaninemics and two healthy controls were investigated. This method allowed a specific differentiation between PKU's, hyperphenylalaninemics and health controls. The remaining enzyme activity in hyperphenylalaninemics and in PKU patients can be estimated with relatively high accuracy. The hyperphenylalaninemic patients showed 7--17% of the phenylalanine-4-hydroxylase activity found in the two control persons. The PKU patients under diet showed approximately 2--3% of the activity found in the control group. In the PKU patients, loaded while showing high phenylalanine blood concentrations, no remaining activity could be measured. The logarithm of phenylalanine-d5 over tyrosine-d4 in plasma 1 h after loading gives the best differentiation. One single plasma sample of approximately 0.5 ml is sufficient.

Adult↗
PubMed1977

Quantitation of deuterated and non-deuterated phenylalanine and tyrosine in human plasma using the selective ion monitoring method with combined gas chromatography-mass spectrometry. Application to the in vivo measurement of phenylalanine-4-monooxygenase activity.

A specific method is described for the quantitative analysis of deuterated and non-deuterated phenylalanine and tyrosine in human plasma by gas chromatography-mass spectrometry using selective ion monitoring. From the several derivatives investigated, the N- or N,O-trifluoroacetyl methyl esters were found to be the most suitable for our purposes. DL-Phenylalanine-4-d1 and L-tyrosine-d7 were used as internal standards. The sensitivity of this method permits the measurement of amounts as small as ca. 2.5 ng/ml in plasma for both phenylalanine and tyrosine. The coefficients of variation were found to be ca. 1.6% (n = 12) for phenylalanine and 3.0% (n = 12) for tyrosine. Using this method, an in vivo determination of phenylalanine-4-monooxygenase activity in humans is possible by loading the subjects with deuterated L-phenylalanine-d5 (accepted as substrate by phenylalanine-4-monooxygenase E.C. 1.14.16.1) and the subsequent measuring of deuterated L-tyrosine-d4 formed and residual L-phenylalanine-d5.

Chromatography, Gas↗
PubMed1976

Study of the intestinal tyrosine metabolism using stable isotopes and gas chromatography-mass spectrometry.

Deuterated tyrosine, 4-hydroxyphenyllactic acid, 4-hydroxyphenylpropionic acid, 4-hydroxyphenylacetic acid and 4-hydroxybenzoic acid were incubated under anaerobic conditions with human faecal specimens for the in vitro study of their respective metabolisms. After 1 week, aromatic acids and phenols were extracted and analyzed by gas chromatography-mass spectrometry. [3',5'-2H2]Tyrosine produced 4-hydroxyphenyllactic acid, 4-hydroxyphenylpropionic acid and 4-hydroxyphenylacetic acid; [3',5'-2H2]-4'-hydroxyphenyllactic acid produced 4-hydroxyphenylpropionic acid, 3-hydroxyphenylpropionic acid, 4-hydroxyphenylacetic acid and phenylproionic acid; [3',5'-2H2]-4'-hydroxyphenyl-propionic acid produced 3-hydroxyphenylpropionic acid and phenylpropionic acid; [3',5',2,2-2H4]-4'-Hydroxyphenylacetic acid produced p-cresol; and [3',5'-2H2]-4'-hydroxybenzoic acid produced phenol. Thus the intestinal flora showed activities for decarboxylation leading to phenol and p-cresol, dehydroxylation leading to phenylpropionic acid and rearrangement leading to 3-hydroxyphenylpropionic acid. Rentention of both deuterium labels was observed in the rearrangement reaction.

Anaerobiosis↗
PubMed1975

Mass fragmentography of 5-hydroxytryptophol and 5-methoxytryptophol in human cerebrospinal fluid.

A specific and very sensitive method for the determination of 5-hydroxy-tryptophol (5-HTOL) and 5-methoxytryptophol (5-MTOL) in extracts from human cerebrospinal fluid (CSF) involving the use of mass fragmentography and pentafluoropriopionyl derivatives is described. 5-HTOL and 5-MTOL were determined in human CSF of three patients with leukaemia and from nine patients with neurological disorders. The concentration of free 5-HOT in CSF was in the range of 0.1-33 ng/ml and that of 5-MTOL was 0.3-13.9 ng/ml. For the first time the presence of these compounds in human material has been shown. The concentration of these two alcohols in CSF is markedly lower than the concentration of 5-hydroxyindoleacetic acid. These results suggest that human cerebral 5-hydroxytryptamine is preferentially metabolized to 5-HTOL-hydroxyindoleacetic acid rather than to 5-HTOL and 5-MTOL.

Adolescent↗