title: Protein metabolism in phenylketonuria and Lesch-Nyhan syndrome.
abstract: Animal and in vitro studies have implicated decreased protein synthesis in the pathogenesis of tissue damage in phenylketonuria (PKU) and of growth failure in Lesch-Nyhan syndrome. Protein turnover was measured in vivo in ten young adult subjects with classical PKU, two subjects with hyperphenylalaninemia, and three children with Lesch-Nyhan syndrome using techniques based on continuous infusions of [13C]leucine and, in Lesch-Nyhan subjects, [2H5]phenylalanine. The PKU subjects had various degrees of dietary phenylalanine restriction and plasma phenylalanine levels at the time of study ranged from 450-1540 mumol/L (mean 1106). Plasma phenylalanine in the two hyperphenylalaninemic subjects was 533 and 402 mumol/L. Rates of protein synthesis in all PKU subjects (mean 3.71 g/kg/24 h, range 2.68-5.10, [13C]leucine as tracer) were in a range similar to or above control values (mean 2.97, range 2.78-3.22, n = 6), as were rates of protein catabolism (PKU mean 4.23 g/kg/24 h, range 3.15-5.45; controls 3.64, 3.50-3.91). Protein turnover values in hyperphenylalaninemia were also similar to those in controls. With [13C]leucine as tracer, both mean protein synthesis and catabolism values in Lesch-Nyhan subjects (mean 4.80 and 5.64 g/kg/24 h, respectively) were higher than values in control children matched for protein intake (synthesis 4.32 +/- 0.74 (SD) and catabolism 4.85 +/- 0.57 (g/kg/24 h, n = 5). Similar results were obtained in Lesch-Nyhan subjects using [2H5]phenylalanine as tracer. These results suggest that protein turnover is not decreased in either PKU or Lesch-Nyhan syndrome. This conclusion is inconsistent with the hypothesis that tissue damage in PKU results from impaired protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Nutrition Research Group, Clinical Research Centre, Harrow, United Kingdom.
authors.forename: G N
authors.initials: GN
authors.lastname: Thompson
authors.forename: P J
authors.initials: PJ
authors.lastname: Pacy
authors.forename: R W
authors.initials: RW
authors.lastname: Watts
authors.forename: D
authors.initials: D
authors.lastname: Halliday
mesh_terms: D000293:Adolescent; D000328:Adult; D000596:Amino Acids / Q000097:blood; D005260:Female; D006130:Growth Disorders / Q000209:etiology / Q000378:metabolism; D006801:Humans; D007926:Lesch-Nyhan Syndrome / Q000150:complications / Q000378:metabolism*; D007930:Leucine / Q000097:blood; D008297:Male; D008875:Middle Aged; D010649:Phenylalanine / Q000097:blood; D010661:Phenylketonurias / Q000209:etiology / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D011506:Proteins; D010649:Phenylalanine; D007930:Leucine