Intermittent Fugu parathyroid hormone 1 (1–34) is an anabolic bone agent in young male rats and osteopenic ovariectomized rats

Human parathyroid hormone (hPTH) is currently the only treatment for osteoporosis that forms new bone. Previously we described a fish equivalent, Fugu parathyroid hormone 1 (fPth1) which has hPTH-like biological activity in vitro despite fPth1(1–34) sharing only 53% identity with hPTH(1–34). Here we demonstrate the in vivo actions of fPth1(1–34) on bone. In study 1, young male rats were injected intermittently for 30 days with fPth1 [30 μg–1000 μg/kg body weight (b.w.), (30fPth1–1000fPth1)] or hPTH [30 μg–100 μg/kg b.w. (30hPTH–100hPTH)]. In proximal tibiae at low doses, the fPth1 was positively correlated with trabecular bone volume/total volume (TbBV/TV) while hPTH increased TbBV/TV, trabecular thickness (TbTh) and trabecular number (TbN). 500fPth1 and 1000fPth1 increased TbBV/TV, TbTh, TbN, mineral apposition rate (MAR) and bone formation rate/bone surface (BFR/BS) with a concomitant decrease in osteoclast surface and number. In study 2 ovariectomized (OVX), osteopenic rats and sham operated (SHAM) rats were injected intermittently with 500 μg/kg b.w. of fPth1 (500fPth1) for 11 weeks. 500fPth1 treatment resulted in increased TbBV/TV (151%) and TbTh (96%) in the proximal tibiae due to increased bone formation as assessed by BFR/BS (490%) and MAR (131%). The effect was restoration of TbBV/TV to SHAM levels without any effect on bone resorption. 500fPth1 also increased TbBV/TV and TbTh in the vertebrae (L6) and cortical thickness in the mid-femora increasing bone strength at these sites. fPth1 was similarly effective in SHAM rats. Notwithstanding the low amino acid sequence homology with hPTH (1–34), we have clearly established the efficacy of fPth1 (1–34) as an anabolic bone agent.

The role of His-134, -147, and -150 residues in subunit assembly, cofactor binding, and catalysis of sheep liver cytosolic serine hydroxymethyltransferase

In an attempt to unravel the role of conserved histidine residues in the structure-function of sheep liver cytosolic serine hydroxymethyltransferase (SHMT), three site-specific mutants (H134N, H147N, and H150N) were constructed and expressed, H134N and H147N SHMTs had K-m values for L-serine, L-allo-threonine and beta-phenylserine similar to that of wild type enzyme, although the k(cat) values were markedly decreased, H134N SHMT was obtained in a dimeric form with only 6% of bound pyridoxal 5'-phosphate (PLP) compared with the wild type enzyme, Increasing concentrations of PLP (up to 500 mu M) enhanced the enzyme activity without changing its oligomeric structure, indicating that His-134 may be involved in dimer-dimer interactions, H147N SHMT was obtained in a tetrameric form but with very little PLP (3%) bound to it, suggesting that this residue was probably involved in cofactor binding, Unlike the wild type enzyme, the cofactor could be easily removed by dialysis from H147N SHMT, and the apoenzyme thus formed was present predominantly in the dimeric form, indicating that PLP binding is at the dimer-dimer interface, H150N SHMT was obtained in a tetrameric form with bound PLP, However, the mutant had very little enzyme activity (<2%). The k(cat)/K-m values for L-serine, L-allo-threonine and beta-phenylserine were 80-, 56-, and SS-fold less compared with wild type enzyme, Unlike the wild type enzyme, it failed to form the characteristic quinonoid intermediate and was unable to carry out the exchange of 2-S proton from glycine in the presence of H-4-folate. However, it could form an external aldimine with serine and glycine, The wild type and the mutant enzyme had similar K-d values for serine and glycine, These results suggest that His-150 may be the base that abstracts the alpha-proton of the substrate, leading to formation of the quinonoid intermediate in the reaction catalyzed by SHMT.

Sapientia, 1979, Vol. XXXIV, nº 133-134 (número completo)

Contenido: El orden humano / Octavio N. Derisi – Los primeros principios / Gustavo E. Ponferrada – La filosofía analítica actual y su terapia mediante la filosofía cristiana y tomista / Teófilo Urdánoz – Verdad y relativismo según el pensamiento de Tomás de Aquino / William R. Darós – El mundo espiritual de la persona / Octavio N. Derisi – Ordo et mysterium / Emilio Komar – La filosofía cristiana de la libertad / Abelardo Lobato – El significado de la encíclica “Aeterni Patris” de León XIII, a los cien años de su publicación / Octavio N. Derisi – Notas y comentarios -- Bibliografía

Diário da Constituinte [gravação de vídeo] : [programa n. 134]

Após muita discussão e duas reuniões das lideranças partidárias, foi aprovado na Comissão de Sistematização o projeto da nova Constituição. Fernando Henrique Cardoso (PMDB-SP) diz que houve acordo entre as lideranças para a votação do projeto formulado por Bernardo Cabral (PMDB-AM). Sandra Cavalcanti (PFL-RJ) fez críticas ao trabalho de Bernardo Cabral, mas depois desmentiu o que foi divulgado pela imprensa. Afonso Arinos (PFL-RJ) lê nota citando o desmentido e dando integral apoio ao Relator Bernardo Cabral. Gasthone Righi (PTB-SP) quer que a Comissão de Sistematização continue apreciando as emendas dos constituintes. Cronograma dos trabalhos na Assembleia Nacional Constituinte (ANC) : discussão e apresentação de emendas no dia 14 de julho; fim do prazo para apresentar emendas no dia 14 de agosto; encerramento da primeira fase de discussão em Plenário no dia 24 de Agosto ; a Comissão de Sistematização volta a discutir o projeto no dia 25 de agosto; encerramento do prazo para votação do substitutivo na Comissão de Sistematização no dia 20 de Setembro; início da votação em 1º turno no Plenário no dia 23 de setembro. Se todos os prazos forem cumpridos, a nova Constituição será promulgada ainda em 1987 e entrará em vigor no dia 1º de janeiro de 1988. Percival Muniz (PMDB-MT) incentiva a população a participar dos debates da Assembleia Constituinte.