Search

Pathological-length polyglutamine (Q[sub n]) expansions, such as those that occur in the huntingtin protein (htt) in Huntington's disease (HD), are excellent substrates for tissue transglutaminase in vitro, and transglutaminase activity is increased in post-mortem HD brain. However, direct evidence for the participation of tissue transglutaminase (or other transglutaminases) in HD patients in vivo is scarce. We now report that levels of N[sup ε]-(γ-l-glutamyl)-l-lysine (GGEL) – a ‘marker’ isodipeptide produced by the transglutaminase reaction – are elevated in the CSF of HD patients (708 ± 41 pmol/mL, SEM, n = 36) vs. control CSF (228 ± 36, n = 27); p < 0.0001. These data support the hypothesis that transglutaminase activity is increased in HD brain in vivo. [ABSTRACT FROM AUTHOR]

We have utilized stable isotopes to measure in vivo rates of urea-genesis. In one testing procedure, 15NH4Cl was administered orally to con-trols and to heterozygotes for ornithine transcarbamylase deficiency. Controls produced [15N]urea at a rate that was greater than that of symptomatic carriers, but indistinguishable from that of asymptomatic carriers. In contrast, both symptomatic and asymptomatic heterozygotes produced [5-15N]glutamine more rapidly than the controls. Ureagenesis could also be measured by administering sodium [1-13C]acetate to a healthy adult and measuring subsequent formation of [13C]urea. The latter approach involves the use of isotope ratio mass spectrometry to determine isotopic abundance. This technique is much more sensitive than gas chromatography–mass spectrometry for the measurement of isotopic label, a consideration that makes the method more suitable for the study of subjects in whom ureagenesis is severely compromised, for example the human male neonate with a near complete deficiency of ornithine transcarbamylase. [ABSTRACT FROM AUTHOR]