Foetal growth and increased urinary excretion of 5-oxoproline in Trinidadian infants

Size at birth is related to the risk of heart disease, hypertension and diabetes mellitus in later life. Glycine is a conditionally essential amino acid during the perinatal period. The urinary execretion of 5-1-oxoproline has been used as a marker for glycine sufficiency. In Jamaican infants, excretion increased progressively during the first weeks of life and by 6 weeks of age was two-to-three times that seen in infants in the UK. We measured the rate of excretion in 42 infants aged 4-to-6 weeks, delivered at Mount Hope Maternity Hospital (Indian, 17; African, 15; mixed, 10), compared with 22 Caucasian infants born in Southampton. There were no differences between the groups in maternal age, maternal haemoglobin, or parity. Trinidadian infants were statistically significantly lighter, with smaller head circumference than the infants in UK. The differences in weight were more marked for the Indian and mixed infants than for the African infants, although head circumference in the three groups was similar. There was a highly statistically significant increase in the excretion of 5-oxoproline in all groups of Trinidadian infants, compared with UK infants. Maternal haemoglobin related to newborn size. When maternal haemoglobin was controlled, there was a statistically significant inverse relationship between 5-oxoproline excretion and birthweight (r=-0.32, p=0.02) and head circumference (r=-0.27, p=0.05). Infants in Trinidad had levels of urinary 5-oxoproline similar to those found previously in Jamaica and about twice those seen in infants in the UK. These differences do not appear to be accounted for by infant feeding patterns, but may be directly related to aspects of maternal nutrition, and the shape and size of the infant at birth. The data suggest that the availability of glycine might be limiting for foetal growth in the Caribbean, and this could have important implications for the development of diabetes mellitus, hypertension and heart disease in later life (AU)

Renal transport and metabolism of glutamine

The experiments described in this thesis were designed to investigate the mechanism of glutamine transport and the effect of acute acidosis on glutamine transport and metabolism in the rat kidney. The experiments done with kidney slices investigated the effect of several amino acids chosen from different structural groups on uptake of glutamine. Proline (an ammino acid) and glycine (at inhibitory concentrations) were found to inhibit ammonia production and glutamine uptake significantly. When a sodium free incubation buffer was used the inhibitory effect of proline and glycine on glutamine uptake disappeared, indicating that the inhibition by proline was sodium dependent. In similar experiments with isolated kidney proximal tubules in a sodium containing buffer, proline also caused a decrease in glutamine uptake and ammonia production. Intracellular/extracellular glutamine distributions ratios in tubules however, showed a marked increase in the presence of proline. The explanation for this is not that proline shares a transport site with glutamine but rather that it is metabolised to glutamate which causes an inhibition of phosphate dependent glutaminase and hence decreased glutamine utilisation. This decreased utilisation leads to an accumulation of glutamine within the renal cell and subsequently increased intracellular/extracellular glutamine distribution ratios. The inhibitory effect of proline on glutamine uptake was much less in experiments with kidney slices from chronically acidotic rats. Isolated tubules from acutely acidotic rats showed increased intracellular/extracellular glutamine distribution ratios, increased ammonia production and glutamine uptake in tubules. When tubules from normal rats were incubated in sera from acutely acidotic rats there was a similar increase in intracellular/extracellular glutamine distribution ratios, ammonia production and glutamine uptake. The effect of the serum however, was not due to the accumulation of glutamate because glutamate levels in tubules were unchanged after incubation in sera from the acutely acidotic rats (AU)

PEST sequences in calmodulin-binding proteins

Many short-lived proteins which are devoid of proteolytic activity contain PEST sequences which are segments along polypeptide chain that are rich in proline (P), glutamate (E), serine (S) and threonine (T). These designated PEST sequences are believed to be putative intramolecular signals for rapid proteolytic degradation. Calmodulin is a ubiquitous, 17 kDa, acidic Ca2+-binding protein which plays an important role in the regulation of many physiological processes through its interaction with a wide range of calmodulin-building proteins. Several calmodulin-binding proteins are known to contain PEST sequences and are susceptible to proteolysis by endogenous neutral proteases such as calpain I and calpain II. In this report, we discuss the functions of PEST sequences in calmodulin-binding proteins and assess the correlation between calmodulin-binding proteins and PEST sequences (AU)