No abstract

Urinary excretion of the non-reusable modified RNA catabolites pseudouridine (psi), 7-methylguanine (m7Gua) and N2,N2-dimethylguanosine (m2(2)Guo) was measured in preterm infants and in adults. The values (in mumol/mmol of creatinine) were: for preterm and 'small for gestational age' infants (n = 26; number of samples = 38) psi = 164 (SD 32), m7Gua = 39.1 (SD 9.0), m2(2)Guo = 10.6 (SD 2.1); for adults (n = 32) psi = 25.3 (SD 3.1), m7Gua = 4.8 (SD 0.89), m2(2)Guo = 1.53 (SD 0.42). Our measurements were compared with an expectation derived from the average cellular distribution of psi, m7Gua and m2(2)Guo between rRNA, tRNA and mRNA. m2(2)Guo occurs exclusively in tRNA, psi in both rRNA and tRNA, and m7Gua in all three RNA classes, in proportions which can be estimated for the steady state. Urinary excretion of psi and m2(2)Guo should reflect their steady-state distribution, since rRNA and tRNA have been shown to have similar turnover rates in mammalian tissues. We conclude that we can use the excretion of m2(2)Guo to assess whole-body tRNA turnover. Since tRNA contains psi in a constant proportion to m2(2)Guo, the proportion of urinary psi stemming from tRNA can be estimated, and the remainder (approximately 60-65%) is an indicator of rRNA turnover. Finally, the excretion of m7Gua far exceeds the proportion predicted to come from rRNA and tRNA. We ascribe this excess (approximately 60-70% of the total) to the turnover of the mRNA 'cap'-structure, which is typical for all higher organisms. mRNA turnover is known to be much higher than that or rRNA or tRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Whole-body degradation rates of transfer, ribosomal, and messenger RNA were determined noninvasively in 3-, 6-, 10-, 14-, and 18-y-old female and male subjects (n = 14 per age group per sex) under normal living conditions. The method for determining the RNA degradation rates is based on measuring the renal excretion rates of special RNA catabolites (modified ribonucleosides and nucleobases) by HPLC. Resting metabolic rates were calculated for the same subjects by their body weights using formulas taken from literature. We found high correlations between the degradation rates of the different RNA classes (micromoles per day per kilogram body weight) and the resting metabolic rate (kilojoules per day per kilogram body weight): in females (n = 70), r = 0.75-0.82 and in males (n = 70), r = 0.68-0.79 (p<0.0001). We conclude that a causal relationship exists between the whole-body degradation rates of the different RNA classes and the resting metabolic rate. Therefore, in healthy subjects noninvasive determinations of RNA degradation rates could be very useful to assess the resting metabolic rate.

No abstract

No abstract

No abstract

Urinary excreted RNA and DNA catabolites are used as noninvasive markers for metabolic processes: 8-oxo-2'-deoxyguanosine (8-oxodG) potentially represents oxidative stress to DNA/deoxyribonucleotidetriphosphate pool, modified ribonucleoside pseudouridine (psi) originating mainly from degraded rRNA and tRNA reflects RNA turnover. Modified amino acid gamma-carboxyglutamic acid (Gla) stems from degraded proteins reflecting turnover of proteins. Aim of the present study was to investigate (44 healthy males, 3-18 y) how excretion rates of 8-oxodG, psi, and Gla are related to resting metabolic rate and energy intake. Excretion rates of 8-oxodG (pmol/kg/d), psi (micromol/kg/d), and Gla (micromol/kg/d) were significantly correlated with resting metabolic rate (kJ/kg/d): r = 0.108 (p = 0.029), 0.691 and 0.552 (p < 0.0001), respectively. Excretion rates of 8-oxodG, psi, and Gla were also significantly correlated with energy intake (kJ/kg/d): r = 0.108 (p = 0.036), 0.602 and 0.462 (p < 0.0001). 8-oxodG and Gla excretion was significantly correlated with psi excretion: r = 0.174 (p = 0.005) and 0.709 (p < 0.0001). These results indicate close relationships between whole-body RNA and protein degradation and metabolic rate. The relationship between 8-oxodG excretion and metabolic rate, however, is less strong suggesting that factors other than metabolic rate considerably affect the oxidative stress to DNA.

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.