Protein and RNA Turnover in Preterm Infants and Adults: A Comparison Based on Urinary Excretion of 3-Methylhistidine and of Modified One-Way RNA Catabolites

Abstract

Urinary excretion of 3-methylhistidine in preterm infants (n = 42; 1,712 ± 408 g, 4–91 days old) was 24.2 ± 6 µmol/mmol creatinine or 2.26 ± 0.56 µmol/kg body weight-day. In adults (n = 6; 66 ± 10 kg, 17–50 years), the corresponding values were 10.5 ± 1.1 µmol/mmol creatinine and 2.21 ± 0.23 µmol/kg body weight-day. For both collectives, the breakdown per kg body weight of 3-methylhistidine-containing protein (i.e. actin and myosin) was similar, at approximately 0.7 g/kg·day (preterm infants 0.84, adults 0.60). Since the preterm infants studied contain ∼21% muscle instead of the 43% found in adults, the 3-methylhistidine excretion in preterm infants probably indicates muscle (and intestinal) protein turnover to be about 3 times higher than in adults, a figure in accord with data on whole-body protein turnover in preterm infants and adults (∼ 15 g/kg·day and ∼ 4 g/kg·day, respectively). Urinary excretion of pseudouridine (ψ), 7-methylguanine (m⁷Gua) and N², N²-dimethyl-guanosine (m²₂G) can be used to estimate the turnover of rRNA, mRNA and tRNA, respectively. The values obtained (in µmol/mmol creatinine) in preterm infants are for ψ: 164 ± 32; for m⁷Gua: 39.1 ± 9; and for m²₂ 10.6 ± 2.1. In adults, the values are for ψ: 25.3 ± 3.1; for m⁷Gua: 4.8 ± 0.89; and for m²₂G: 1.53 ± 0.38. This yields 3–4 times higher turnover rates in preterm infants than in adults for all 3 RNA classes: rRNA, 0.1 versus 0.038; tRNA, 1.87 versus 0.66; mRNA 2.35 versus 0.64 µmol/kg·day. Thus all data indicate that preterm infants have a 3- to 4-fold higher turnover than adults not only of whole-body protein, but also of rRNA, tRNA and mRNA.

Clinical significance and prognostic value of urinary nucleosides in breast cancer patients

“…Because whole-body RNA turnover correlates quite well with protein turnover [28], attention should be paid to the alterations of urinary nucleosides under various catabolic conditions other than those occurring in malignancies, for example, inflammation, malnutrition, endocrine abnormalities, and alcoholism. In our investigation of 23 patients with hepatitis and 26 patients with liver cirrhosis, false-positive results were less than 7% based on the metabonomics method.…”

Cellular proteolysis and systemic inflammation during exacerbation in cystic fibrosis

“…Generally methods to determine protein turnover are not applicable to routine clinical use or large group investigations, because they are laborious and costly [8,13]. The urinary excretion of methylated nucleosides has been previously used as a non-invasive method for the assessment of protein metabolism [9].…”

“…Excretion of PSU has been validated against amino-acid infusion and used to assess cell turnover in inflammatory diseases, leukaemia, lymphomas, and solid tumours [8][9][10][11][12]. PSU is derived from RNA breakdown, is independent of diet, is neither metabolised further nor re-incorporated, and hence indicates cell turnover and cell-derived protein breakdown.…”

Modulation of circulating purines and pyrimidines by physical exercise in the horse

“…In our trained horses, either at 5 or at 30 min after the SET, a significant increase in plasma b-pseudouridine was also observed. Since this modified pyrimidine is exclusively found in transfer and ribosomal RNAs, its increase in body fluids is generally considered as an index of increased rate of RNAs turnover, due to increased rate of protein synthesis (Sander et al 1986). Increase in the rate of protein synthesis following physical exercise has been demonstrated both in human beings (Dreyer et al 2010) and in horses (McGivney et al 2009).…”

“…The compound b-pseudouridine is generated during the degradation of structural RNAs and is not salvaged by the body once released from the tissues (Weissman et al 1962). Consequently, its determination has been used as an indicator of protein synthesis, assuming that increased protein synthesis requires increased RNA turnover (Sander et al 1986;Schöch et al 1990). In this light, several studies in humans have evaluated the clinical utility of b-pseudouridine detection in body fluids as a potential biomarker for the diagnosis of different types of tumors (Liebich et al 2005;Masaki et al 2006).…”