RESUMO
Several factors that may contribute to the stabilization of the helical structure in proteins, detected in studies made on short synthetic peptides, have been reported. Some of them are: presence of alanine or leucine, ionic-pair bonding, stabilization of the helical dipole moment by appropriate charges at the helix N- and C-caps, and aromatic interactions of amino acids located at positions i, i + 4. An analysis of 54 helical structures from 12 proteins showed that all these stabilizing factors were also present in proteins, but the influence of any of them had a different weight, according to the distribution of the hydrophobic and hydrophilic amino acid residues in the helical sequence. The role of non-sequence depending interactions in helical stability, such as presence of disulfide bridges, or bonding of helical residues to substrate and/or cofactors, was also analysed.
Assuntos
Alanina/fisiologia , Aminoácidos/fisiologia , Estabilidade Enzimática/fisiologia , Leucina/fisiologia , Muramidase/ultraestrutura , Hormônios Pancreáticos/fisiologia , Estrutura Secundária de ProteínaRESUMO
Several factors that may contribute to the stabilization of the helical structure in proteins, detected in studies made on short synthetic peptides, have been reported. Some of them are: presence of alanine or leucine, ionic-pair bonding, stabilization of the helical dipole moment by appropriate charges at the helix N- and C-caps, and aromatic interactions of amino acids located at positions i, i + 4. An analysis of 54 helical structures from 12 proteins showed that all these stabilizing factors were also present in proteins, but the influence of any of them had a different weight, according to the distribution of the hydrophobic and hydrophilic amino acid residues in the helical sequence. The role of non-sequence depending interactions in helical stability, such as presence of disulfide bridges, or bonding of helical residues to substrate and/or cofactors, was also analysed
Assuntos
Alanina/fisiologia , Aminoácidos/fisiologia , Estabilidade Enzimática/fisiologia , Leucina/fisiologia , Muramidase/ultraestrutura , Hormônios Pancreáticos/fisiologia , Estrutura Secundária de ProteínaAssuntos
Humanos , Pâncreas/metabolismo , Insulina/fisiologia , Glucagon/fisiologia , Hormônios Pancreáticos/biossíntese , Receptores de Hormônios Pancreáticos/metabolismo , Glucagon/biossíntese , Somatostatina/biossíntese , Somatostatina/fisiologia , Polipeptídeo Pancreático/biossíntese , Polipeptídeo Pancreático/fisiologia , Hormônios Pancreáticos/fisiologia , Hormônios Pancreáticos/metabolismo , Insulina/análogos & derivados , Insulina/biossíntese , Receptor de Insulina/biossíntese , Receptor de Insulina/metabolismoAssuntos
Humanos , Glucagon/fisiologia , Hormônios Pancreáticos/biossíntese , Insulina/fisiologia , Pâncreas/metabolismo , Receptores de Hormônios Pancreáticos/metabolismo , Glucagon/biossíntese , Hormônios Pancreáticos/fisiologia , Hormônios Pancreáticos , Insulina/análogos & derivados , Insulina/biossíntese , Polipeptídeo Pancreático/biossíntese , Polipeptídeo Pancreático/fisiologia , Receptor de Insulina/biossíntese , Receptor de Insulina/metabolismo , Somatostatina/biossíntese , Somatostatina/fisiologiaRESUMO
To study the role of enteroinsular hormones in fetal macrosomia and neonatal hypoglycemia in infants of diabetic mothers, we measured plasma concentrations of free and total immunoreactive insulin, C-peptide, pancreatic glucagon, enteroglucagon, and gastric inhibitory polypeptide at birth in 35 IDMs and 35 infants of normal mothers. Twenty fasting adults of normal weight were also studied. Sixteen IDMs were macrosomic at birth; 17 developed neonatal hypoglycemia over the first postnatal hours. The IDMs had ten times higher concentrations of free IRI than the normal infants in cord blood. Free IRI concentrations were related to the severity of maternal diabetes, with the infants of white class D to F mothers having the highest levels. The IDMs with macrosomia had a twofold increase in the concentrations of free IRI when compared with IDMs of normal weight. There was a significant correlation between the birth weight ratio and the concentrations of free IRI. The IDMs who developed neonatal hypoglycemia had considerably higher concentrations of free IRI than did normoglycemic IDMs. The decrease of blood glucose over the first postnatal hours correlated strongly with the free IRI concentrations in the cord blood. The IDMs had a threefold increase of the C-peptide concentrations over those in normal infants. Six IDMs had a molar ratio of C-peptide to free IRI of less than 1. Both the IDMs and normal infants had substantially higher concentrations of enteroglucagon and lower concentrations of GIP than did the fasting adults. Our data provide direct evidence that IDMs are markedly hyperinsulinemic at birth and that ambient hyperinsulinemia plays a crucial role in the development of fetal macrosomia and neonatal hypoglycemia. Moreover, the observed discrepancy in the relative increase of free IRI and C-peptide, combined with the low molar ratio of C-peptide to IRI, suggests a decreased metabolic clearance of insulin or transplacental passage of insulin from the maternal circulation in infants of mothers with insulin-treated diabetes.