GDAP1 mutations are frequent among Brazilian patients with autosomal recessive axonal Charcot-Marie-Tooth disease.

Mutations in ganglioside-induced differentiation-associated-protein 1 (GDAP1) are associated with several subtypes of Charcot-Marie-Tooth (CMT) disease, including autosomal recessive and demyelinating (CMT4A); autosomal recessive and axonal (AR-CMT2K); autosomal dominant and axonal (CMT2K); and an intermediate and recessive form (CMTRIA). To date, at least 103 mutations in this gene have been described, but the relative frequency of GDAP1 mutations in the Brazilian CMT population is unknown. In this study, we investigated the frequency of GDAP1 mutations in a cohort of 100 unrelated Brazilian CMT patients. We identified five variants in unrelated axonal CMT patients, among which two were novel and probably pathogenic (N64S, P119T) one was novel and was classified as VUS (K207L) and two were known pathogenic variants (R125* and Q163*). The prevalence rate of GDAP1 among the axonal CMT cases was 7,14% (5/70), all of them of recessive inheritance, thus suggesting that the prevalence was higher than what is observed in most countries. All patients exhibited severe early-onset CMT that was rapidly progressive. Additionally, this study widens the mutational spectrum of GDAP1-related CMT through identification of two novel likely pathogenic variants.

Arthrobacter oxydans as a biocatalyst for purine deamination.

Deaminases are enzymes that catalyze the hydrolysis of amino groups of nucleosides or their bases. Because these enzymes play important roles in nucleotide metabolism, they are relevant targets in anticancer and antibacterial therapies. Mammalian deaminases are commercially available but the use of bacterial whole cells, especially as biocatalysts, is continuously growing because of their economical benefits. Moreover, deaminases are useful for the preparative chemoenzymatic transformation of nucleoside and base analogues into a variety of derivatives. The purine deaminase activities of Arthrobacter oxydans, a gram-positive bacterium utilized widely in bioremediation, were studied. The presence of adenosine, adenine and guanine deaminases was demonstrated and some purine bases and nucleosides were analyzed as substrates. Using A. oxydans whole cells as the biocatalyst, different purine compounds such as the anti-HIV, 2',3'-dideoxyinosine (73%, 2 h) were obtained.

Guanasa y metabolitos en pancreatitis isquemica experimental / Guanase and metabolites in experimental ischemic pancreatitis

El dano provocado por la pancreatitis experimental en perros, determina un aumento significativo de la actividad de la Guanasa. Este aumento se produce a las 2 hs de la isquemia en tejidos y a las 24 hs en suero. Asi mismo se determina que la actividad es similar en cabeza y cola y está ausentela actividad en el cuerpo del páncreas. Finalmente se observa que mientras las oxipurinas séricas, aumentan en forma similar a la Guanasa sérica, la Guanina sé-rica, disminuye significativamente recién a las 24 hs. Estos resultados indicanque la actividad de guanasa es un excelente "marcador" del dano pancreático en perros

Enzimas y metabolitos purínicos durante el embarazo / Purine metablic enzymes during of pregnancy

Se estudia el metabolismo purínico en 64 mujeres, 48 embarazadas y 16 no embarazadas. Los resultados se confrontaron estadísticamente y se concluye que: no se observa actividad de guanasa, a diferencia del suero, en saliva de mujeres embarazadas o no embarazadas. Las oxipurinas, xantina + hipoxantina, salivales, aumentan progresivamente durante el embarazo, siendo los valores más significativos en el 3er. trimestre. El ácido úrico sérico y salival, y la xantina oxidasa salival, disminuyen progresivamente durante la gestación, observando los valores más significativos en el 3er. trimestre. Se establecen los valores normales de xantina oxidasa, oxipurinas y ácido úrico en la saliva de las mujeres estudiadas. (AU)

Enzimas y metabolitos purínicos durante el embarazo / Purine metablic enzymes during of pregnancy

Se estudia el metabolismo purínico en 64 mujeres, 48 embarazadas y 16 no embarazadas. Los resultados se confrontaron estadísticamente y se concluye que: no se observa actividad de guanasa, a diferencia del suero, en saliva de mujeres embarazadas o no embarazadas. Las oxipurinas, xantina + hipoxantina, salivales, aumentan progresivamente durante el embarazo, siendo los valores más significativos en el 3er. trimestre. El ácido úrico sérico y salival, y la xantina oxidasa salival, disminuyen progresivamente durante la gestación, observando los valores más significativos en el 3er. trimestre. Se establecen los valores normales de xantina oxidasa, oxipurinas y ácido úrico en la saliva de las mujeres estudiadas.

Leishmania mexicana: purine-metabolizing enzymes of amastigotes and promastigotes.

Cultured promastigote and isolated amastigote forms of Leishmania mexicana mexicana have been surveyed for the presence of enzymes involved in purine metabolism. Quantitative but not qualitative differences between the enzymes of two forms were discovered. There were found to be significant differences between the enzyme content of L. m. mexicana and that reported for L. donovani. Extracts of both parasite forms of L. m. mexicana were found to have higher levels of adenine deaminase (EC 3.5.4.2) and guanine deaminase (EC 3.5.4.3) than adenosine deaminase (EC 3.5.4.4). There appeared to be two distinct nucleosidases (EC 3.2.2.1), one active on nucleosides, the other on deoxynucleosides. Phosphorylase (EC 2.4.2.1) could be detected only in the catabolic direction. Nucleotidases were present, but were more active on 3' (EC 3.1.3.6)- than 5' (EC 3.1.3.5)-nucleotides. Phosphoribosyltransferase (EC 2.4.2.7,.8 and .22) and nucleoside kinase (EC 2.7.1.20) activities were detected in both forms. Nucleotide-interconverting enzymes were found to be present, with IMP dehydrogenase (EC 1.2.1.14) being the most active. Cell fractionation experiments revealed that, in the promastigote, enzyme separation within the parasite may play an important part in regulating cellular purine metabolism.