European Journal of Biomedical and Pharmaceutical Sciences

ABNORMAL PHENYLALANINE-TYROSINE METABOLISM MAY PLAY A ROLE IN THE DECREASE OF HAEMOGLOBIN IN HEALTHY PREGNANCY: A COHORT STUDY

Imre Tormási, Szilárd Kun, Gerg? Attila Molnár, Attila Miseta, András Szilágyi (†) and István Wittmann*

ABSTRACT

Background: Hyperfiltration and lowering of haemoglobin level are documented changes in physiological pregnancy. Serum level of erythropoietin increases in pregnancy and erythropoietin-resistance develops which may be contributed by elevated levels of hydroxil free radical–derived, pathological products of Phenylalanine as meta- and ortho-tyrosine, in contrast to the physiological para-tyrosine-. Population and methods: Physiological pregnant women (n=23) and healthy, non-pregnant women (n=26) were enrolled. In the pregnant group blood and urine samples were taken at weeks 12, 24, 36 and at delivery. We determined the concentrations of Phe and the three Tyr isoforms using reverse-phase high performance liquid chromatography. The time kinetics of these and their association with hematopoiesis were studied. Tendencies of p-, m-, o-Tyr and Phe levels, as well as erythropoietin and hematopoiesis parameters were determined. Results: In the early pregnancy a decreased serum level of p-Tyr developed (p<0.05). In the progression of the pregnancy, p-, m-, o-Tyr and Phe levels showed an increasing tendency (p<0.05). Serum levels of m- and o-Tyr and their ratios with Phe and p-Tyr correlated inversely with (p<0.05), and were independent predictors of haemoglobin levels (p<0.05). Urinary levels of o-Tyr and its ratios with Phe and p-Tyr correlated with and were predictors of red cell distribution width (p<0.05). We observed decreased serum haemoglobin and elevated serum erythropoietin levels, suggesting erythropoietin resistance. Conclusions: Elevated levels of pathological Tyr isoforms and decreased concentration of p-Tyr are associated with hematopoiesis in physiological pregnancy. Lowered level of p-Tyr can be the result of increased excretion or elevated consumption. We propose that pathological tyrosines may lead to disturbed erythropoiesis.

Keywords: tyrosine, gestational anaemia, EPO-resistance, erythropoiesis, pregnancy.