RESUMO
Peptide isomerase catalyses the post-translational isomerisation of the L: - to the D: -form of an amino acid residue around the N/C-termini of substrate peptides. To date, some peptide isomerases have been found in a limited number of animal secretions and cells. We show here that papaya extracts have weak peptide isomerase activity. The activity was detected in each 30-100 kDa fraction of the flesh and the seed extracts of unripe and ripe papaya fruit. The definitive activity was confirmed in the ripe papaya extracts, but even then it was much less active than that of the other peptide isomerases previously reported. The activity was markedly inhibited by methanol, and partly so by amastatin and diethyl pyrocarbonate. This is the first report of peptide isomerase activity in a plant and suggests that perhaps every living organism may have some peptide isomerase activity.
Assuntos
Carica/enzimologia , Isomerases/isolamento & purificação , Isomerases/metabolismo , Peptídeos/metabolismo , Extratos Vegetais/isolamento & purificação , Fracionamento Químico , Dietil Pirocarbonato/metabolismo , Inibidores Enzimáticos/metabolismo , Metanol/metabolismoRESUMO
We present two mathematical models that describe human red blood cells (RBCs) with morphologies that are attained naturally under certain patho-physiological conditions, namely stomatocytes and echinocytes. Muñoz San Martín et al. (Bioelectromagnetics 27:521-527, 2006) recently presented models of these shapes based on our previous set of parametric equations (Kuchel and Fackerell, Bull. Math. Biol. 61:209-220, 1999) that involve Jacobi elliptic functions and integrals. Thus, both discocytes and stomatocytes are described. Here, we derived the Cartesian forms of these new equations; and, in addition, present a realistic model of a Type III echinocyte, using prolate spheroids 'decorating' a central sphere at the vertices of an internal dodecahedron. The RBC models based on Cartesian equations have been used for representing the shape changes (morphological transformations or "morphing") that occur in RBCs under various experimental conditions; specifically, when the shape changes have been monitored by nuclear magnetic resonance (NMR) micro-imaging.
Assuntos
Forma Celular , Eritrócitos/patologia , Modelos Teóricos , HumanosRESUMO
Ornithine transcarbamylase (OTC) deficiency, the most common urea cycle disorder, is associated with severe hyperammonemia accompanied by a high risk of neurological damage and death in patients presenting with the neonatal-onset form. Contemporary therapies, including liver transplantation, remain inadequate with considerable morbidity, justifying vigorous investigation of alternate therapies. Clinical evidence suggests that as little as 3% normal enzyme activity is sufficient to ameliorate the severe neonatal phenotype, making OTC deficiency an ideal model for the development of liver-targeted gene therapy. In this study, we investigated metabolic correction in neonatal and adult male OTC-deficient Spf(ash) mice following adeno-associated virus (AAV)2/8-mediated delivery of the murine OTC complementary DNA under the transcriptional control of a liver-specific promoter. Substantially supraphysiological levels of OTC enzymatic activity were readily achieved in both adult and neonatal mice following a single intraperitoneal (i.p.) injection, with metabolic correction in adults being robust and life-long. In the neonates, however, full metabolic correction was transient, although modest levels of OTC expression persisted into adulthood. Although not directly testable in Spf(ash) mice, these levels were theoretically sufficient to prevent hyperammonemia in a null phenotype. This loss of expression in the neonatal liver is the consequence of hepatocellular proliferation and presents an added challenge to human therapy.