<scp>l</scp>-Cystathionine in the urine of pyridoxine-deficient rats

Hope, D. B.

doi:10.1042/bj0660486

Cited by 51 publications

(4 citation statements)

References 12 publications

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“…Cystathioninuria was induced experimentally in pyridoxine-deficient rats (Blaschko et al (l), Hope (7)) and is known to occur in pyridoxine-deficiency in man (3,10). The probability of cystathioninuria being an expression of pyridoxine-deficiency in these patients with liver malfunction cannot be decided on the basis of the available data.…”

Section: Discussionmentioning

confidence: 99%

Secondary Cystathioninuria

Studnitz

1969

Acta Paediatrica

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Increased urinary excretion of cystathionine has been reported in 6 patients and was associated in 5 of them with mental retardation. This patient group is interpreted as having an inborn error of metabolism due to a disturbance in the metabolic breakdown of cystathionine (primary cystathioninuria) 1(4). Several reports of increased urinary excretion of cystathionine in children in combination with various diseases, eg. pyridoxine deficiency, neuroblastoma galactosaemia and hepatoblastoma have been published (for review of such cases of secondary cystathioninuria see Shaw et al.)(1 1).The purpose of the present investigation was to study the frequency of cystathioninuria in larger groups of hospitalized children. MATERIAL AND METHODSThe material examined consists of 230 children in whom the urinary aminoacid pattern had been requested on the ground of suspected metabolic disorders, especially in patients with malformation, mental retardation or convulsions. The patients were all hospitalized a t the paediatric department, General Hospital, Malmo. The urine samples from patients had been stored at +4" and were analysed within 3 days.The urinary a-amino nitrogen were measured as described by Khachadurian ef al. (8). The urinary aminoacids were separated by high-voltage paper electrophoresis combined with paper chromatography (13). Samples of urine, which contained 5 mg of creatinine, were initially passed through a 3 cm column of Zeo-Karb 225 resin to remove urea and to reduce volume (2). The concentrated aminoacid solu-12 --692889 Aeta P a d i a t Scand 58 tion corresponding to 75 p g creatinine was then applicated to Whatman No. 3 M M paper and separated by electrophoresis with formateacetic acid, pH = 1.2. The voltage gradient was 40 V per cm; running time 90 minutes. Three parallel runs were performed on the same paper. After electrophoresis two strips were cut away from the large sheet of paper and were stained with ninhydrin (12) iodine-platinate (12) respectively. The last reagent was used for localizing the sulphur-containing aminoacids. The third strip was used for chromatography in the second dimension (n-butanol, acetic acid, water, 12 : 3 : 5 v/v) over night. Under the electrophoretic conditions described methionine and cystine migrated together but cystathionine had a greater migration rate towards the cathode, The only sulphur-containing aminoacid which had the same migration rate as cystathionine under these conditions was homocystine. Chromatography in the second dimension separates these two aminoacids as well as methionine and cystine. The following Rf-values were found: Cystine = 0,08; methionine = 032; homocystine 0,18; and cystathionine = 0,lO.Homocystine was never found. The sensitivity of the iodineplatinate reagent allows detection of cystathionine in concentrations as low as 0.2 p g per spot. The recovery of cystathionine by this method was about 90% thus the lower limit of detection was about 2 mg cystathionine per g creatinine.When a sulphur-positive aminoacid in the area of cystathionine...

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Section: Discussionmentioning

confidence: 99%

Secondary Cystathioninuria

Studnitz

1969

Acta Paediatrica

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“…To our knowledge cystathionine has not been associated to HPP or TNAP dysfunction. In other contexts, studies showed that altered tissue level of cystathionine, brain included, is reflected by increased urinary excretion of cystathionine (Hope , ; Harris et al . ; Kraus et al .…”

Section: Discussionmentioning

confidence: 99%

Identification of altered brain metabolites associated with TNAP activity in a mouse model of hypophosphatasia using untargeted NMR‐based metabolomics analysis

Cruz

Gleizes

Balayssac

et al. 2017

Journal of Neurochemistry

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Tissue Nonspecific Alkaline Phosphatase (TNAP) is a key player of bone mineralization and TNAP gene (ALPL) mutations in human are responsible for hypophosphatasia (HPP), a rare heritable disease affecting the mineralization of bones and teeth. Moreover, TNAP is also expressed by brain cells and the severe forms of HPP are associated with neurological disorders, including epilepsy and brain morphological anomalies. However TNAP’s role in the nervous system remains poorly understood. In order to investigate its neuronal functions, we aimed to identify without any a priori the metabolites regulated by TNAP in the nervous tissue. For this purpose we used 1H- and 31P NMR to analyze the brain metabolome of Alpl (Akp2) mice null for TNAP function, a well-described model of infantile HPP. Among 39 metabolites identified in brain extracts of one week-old animals, 8 displayed significantly different concentration in Akp2−/− compared to Akp2+/+ and Akp2+/− mice: cystathionine, adenosine, GABA, methionine, histidine, 3-methylhistidine, N-acetylaspartate (NAA) and N-acetyl-aspartyl-glutamate (NAAG), with cystathionine and adenosine levels displaying the strongest alteration. These metabolites identify several biochemical processes that directly or indirectly involve TNAP function, in particular through the regulation of ecto-nucleotide levels and of pyridoxal phosphate-dependent enzymes. Some of these metabolites are involved in neurotransmission (GABA, adenosine), in myelin synthesis (NAA, NAAG), and in the methionine cycle and transsulfuration pathway (cystathionine, methionine). Their disturbances may contribute to the neurodevelopmental and neurological phenotype of HPP.

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“…It is nevertheless believed that the separate release of oxytocin and ADH does occur, for suckling causes either no antidiuresis or significantly less than would be expected, while on the other hand antidiuresis provoked by the rapid intravenous injection of a litre of 2 5 % NaCl caused no uterine contractions. (Blaschko & Hope, 1956;Hope, 1957a). It has since been found in relatively high concentration in the brains of man and rhesus monkey (Tallan, Moore & Stein, 1958).…”

Section: Calomel Electrodementioning

confidence: 99%

Proceedings of the Physiological Society

1958

The Journal of Physiology

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l-Cystathionine in the urine of pyridoxine-deficient rats

Cited by 51 publications

References 12 publications

Secondary Cystathioninuria

Secondary Cystathioninuria

Identification of altered brain metabolites associated with TNAP activity in a mouse model of hypophosphatasia using untargeted NMR‐based metabolomics analysis

Proceedings of the Physiological Society

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