Database cloning human delta 1-pyrroline-5-carboxylate synthetase (P5CS) cDNA: a bifunctional enzyme catalyzing the first 2 steps in proline biosynthesis.

delta 1-pyrroline-5-carboxylate synthetase (P5CS) catalyzes the ATP and the NAD(P)H-dependent conversion of L-glutamate to glutamic gamma-semialdehyde (GSA) which is the metabolic precursor for proline biosynthesis. We cloned a human P5CS cDNA by database cloning strategy and sequenced 2,907 bp from this cDNA which has a closed open reading frame (ORF) of 2,385 bp coding for a polypeptide of 795 amino acid residues. This cDNA, as its plant counterpart, encodes a bifunctional enzyme, with both gamma-glutamyl kinase (gamma-GK) and gamma-glutamyl phosphate reductase (gamma-GPR) activities that catalyzes the first 2 steps in proline biosynthesis and it hybridizes to a 4.5 kb mRNA from various tissues. A human genetic disease caused by a deficient P5CS has been recognized. The phenotypic features for deficiency of P5CS include joint hyperlaxity, skin hyperelasticity, cataract and mental retardation with hyperammonemia and low plasma levels of proline, citrulline and ornithine.

Liver transplantation in two cases of propionic acidaemia.

Orthotopic liver transplantation (OLT) was performed in two patients with propionic acidaemia, a 7-year-old boy and a 9-year-old girl, diagnosed with a severe neonatal form with high risk of metabolic decompensation. In both cases the metabolic liver functions recovered within the 12 postoperative hours; no clinical symptoms of propionic acid toxicity, metabolic acidosis, severe hyperammonaemia, hyperglycinaemia or haematological abnormalities were observed. In both cases insulin-dependent diabetes mellitus occurred early after OLT (persisting in the boy's case). Severe post-transplantation complications were observed (acute rejection and CMV infection in both patients) which did not trigger metabolic decompensation. The boy developed chronic rejection and vanishing bile duct syndrome due to incomplete hepatic arterial thrombosis. He required permanent in-patient care with chronic hyperammonaemia and neurological sequelae involving the basal ganglia and died 15 months after OLT. The girl left hospital after 2 months and is presently leading a normal life with almost no dietary protein restriction (40 g protein per day). Urinary urea excretion and daily protein intake increased after liver transplantation. Propionyl- and tiglylglycine disappeared immediately after OLT. Urinary methylcitrate and 3-hydroxypropionate remained at concentrations corresponding to those before OLT. However, the total of all characteristic metabolites of organic acid analysis was reduced to 50-60% of the values before OLT in both patients. Propionylcarnitine was still detected at significant concentrations. Plasma odd-chain fatty acid concentrations decreased continuously after OLT only in the girl's case. Tissue of both transplanted livers showed increased odd-chain fatty acid concentrations 9 and 15 months after OLT, respectively, in both patients. We consider that at present OLT should only be performed in severe forms of propionic acidaemia.

[Bilirubin in the early neonatal period. Is there a positive aspect of hyperbilirubinemia?--A medical hypothesis]. / Bilirubin in der frühen Neugeborenenperiode. Gibt es positive Aspekte einer Hyperbilirubinämie?--Eine medizinische Hypothese.

The fact that almost all neonates exhibit a "physiological" jaundice, prompts the question whether bilirubin, usually exclusively considered a potentially toxic endproduct of the metabolism of heme, might not also have a positive task in the first days of life. A recently discovered property of bilirubin under in vitro conditions is its ability to combine with free oxygen radicals such as are produced in the oxidative metabolic processes of the neonate immediately following birth. In the present article, the concept of the anti-oxidative effect of bilirubin, and its translation to the early neonatal period is presented and discussed on the basis of a number of examples.

Urinary malondialdehyde concentration in preterm neonates: is there a relationship to disease entities of neonatal intensive care?

In a retrospective study, urinary malondialdehyde concentration in 45 preterm neonates (25-35 weeks' gestation) during their first month of life was measured by HPLC. Urine was collected on different days of life as a 3-h sample. The frequency of urine collection and measurement varied between one (n = 22) and seven times (n = 8) per child. The study group was divided into three categories according to birth weight: low-birth-weight infants (LBW) (n = 16), very low-birth-weight infants (VLBW) (n = 17) and extremely low-birth-weight infants (ELBW) (n = 12). Urinary malondialdehyde concentration was highest in the ELBW group: 1.15 (0.66, 2.12) mumol/l (median and quartiles) versus 0.58 (0.34, 1.18) mumol/l in the VLBW and 0.60 (0.40, 1.06) mumol/l in the LBW groups (ELBW versus VLBW, p < 0.005; ELBW versus LBW, p < 0.02). In oxygen-treated neonates, significantly higher malondialdehyde values were found compared to those without supplementary oxygen (0.89 (0.48, 1.74) versus 0.58 (0.32, 0.89) mumol/l; p < 0.005). Likewise, a higher malondialdehyde concentration was found in infants requiring mechanical ventilation (intermittent mandatory IMV or high frequency ventilation) compared to those breathing spontaneously (intermittent mandatory ventilation: 0.80 (0.42, 1.66); p > 0.05 and high frequency ventilation: 1.20 (0.83, 2.13); p < 0.001 versus 0.57 (0.33, 0.88) mumol/l). Malondialdehyde concentrations correlated significantly with FiO2 values of the individual patients (r = 0.22; p < 0.02). Comparing urinary malondialdehyde concentrations in infants with and without bronchopulmonary dysplasia, a significantly higher malondialdehyde concentration was found in the former group (0.96 (0.51, 2.07) versus 0.60 (0.32, 0.98) mumol/l; p < 0.005)).(ABSTRACT TRUNCATED AT 250 WORDS)