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: G N Thompson, P J Pacy, R W Watts, D Halliday
• Journal: Pediatric research (Pediatr Res) Vol. 28 Issue 3 Pg. 240-6 (Sep 1990) ISSN: 0031-3998 [Print] United States
• PMID: 2235121 (Publication Type: Journal Article)

Chemical References

• Amino Acids
• Proteins
• Phenylalanine
• Leucine

Topics

• Adolescent
• Adult
• Amino Acids (blood)
• Female
• Growth Disorders (etiology, metabolism)
• Humans
• Lesch-Nyhan Syndrome (complications, metabolism)
• Leucine (blood)
• Male
• Middle Aged
• Phenylalanine (blood)
• Phenylketonurias (etiology, metabolism)
• Proteins (metabolism)