Orosomucoid

Abstract: : The species specificity which had been observed in rat and human transcortin for the species specific corticosteroid has not been found to be a general phenomenon. The corticosteroidbinding proteins in the sera of various mammalian species belong to the alpha gloublin as was demonstrated by the method of equilibrium paper electrophoresis. Electrophoretic studies showed that the transcortin containing fraction of ran serum migrates faster than albumin at pH values below 7, whereas at higher pH it behaves as an alpha globulin. The alpha- acid glycoprotein (orsomucoid) has been prepared by a combination of precipitation and chromatographic procedures. The interaction of progesterone with this glycoprotein has been found to be highly dependent on temperature; the association constant decreases with increasing temperature. A strong dependency on pH has also been observed; the association constant is highest at pH 8 and decreases to about 1/20 of this value at pH 2.3. The number of binding sites for progesterone has been determined to be n = 1 at pH 7.4, 4 degrees C; the free energy of binding has the relatively high value of -7.5 kilocalories per mole. Partial removal of sialic acid from the orosomucoid preparations reduced the binding affinity for progesterone. In biological assay studies on the ligated uterus horn of the mouse it was observed that progesterone is inactivated by binding to the alphaacid blycoprotein.

Abstract: Liver-specific and nonliver-specific methionine adenosyltransferases (MATs) are products of two genes, MAT1A and MAT2A, respectively, that catalyze the formation of S-adenosylmethionine (AdoMet), the principal biological methyl donor. Mature liver expresses MAT1A, whereas MAT2A is expressed in extrahepatic tissues and is induced during liver growth and dedifferentiation. To examine the influence of MAT1A on hepatic growth, we studied the effects of a targeted disruption of the murine MAT1A gene. MAT1A mRNA and protein levels were absent in homozygous knockout mice. At 3 months, plasma methionine level increased 776% in knockouts. Hepatic AdoMet and glutathione levels were reduced by 74 and 40%, respectively, whereas S-adenosylhomocysteine, methylthioadenosine, and global DNA methylation were unchanged. The body weight of 3-month-old knockout mice was unchanged from wild-type littermates, but the liver weight was increased 40%. The Affymetrix genechip system and Northern and Western blot analyses were used to analyze differential expression of genes. The expression of many acute phase-response and inflammatory markers, including orosomucoid, amyloid, metallothionein, Fas antigen, and growth-related genes, including early growth response 1 and proliferating cell nuclear antigen, is increased in the knockout animal. At 3 months, knockout mice are more susceptible to choline-deficient diet-induced fatty liver. At 8 months, knockout mice developed spontaneous macrovesicular steatosis and predominantly periportal mononuclear cell infiltration. Thus, absence of MAT1A resulted in a liver that is more susceptible to injury, expresses markers of an acute phase response, and displays increased proliferation.