Components of human split ejaculates. II. Enzymes and proteinase inhibitors.
(73/1525)
Lysozyme, alpha-amylase, neutral proteinase and plasminogen activator were most concentrated in the initial portion of the ejaculate that consists mostly of Cowper's gland and prostate gland fluids as well as spermatozoa. The concentration of the high molecular weight proteinase inhibitors, alpha1-antitrypsin and alpha1X-antichymotrypsin, was essentially unaltered throughout the ejaculate fractions, although their absolute amounts showed an increase towards the final fraction. By contrast, the total inhibitory activity towards pancreatic trypsin was highest both in concentration and amount in the last fraction, thus indicating that the seminal vesicles are its primary source. Plasminogen, prothrombin, Factor XIII, and the proteinase inhibitors antithrombin III, alpha2-macroglobulin, inter-alpha-trypsin inhibitor and C1S-inactivator could not be detected immunochemically in whole ejaculates, and indicates the dissimilarity between the coagulation/liquefaction processes of semen and blood. (+info)
'Durate variant with clinical signs' has alpha1 -antitrypsin genotype ZZ.
(74/1525)
A patient with neonatal jaundice and cirrhosis who was previously reported homozygous for the Durate variant of galactose-1-phosphate uridyl transferase has the ZZ genotype for alpha1-antitrypsin. A sister of the patient, also with ZZ genotype, is less severly affected with liver disease and is a heterozygote for the Durate variant. Since a number of patients with ZZ genotype of alpha1-antitrypsin have been previously reported to have liver disease, the latter genotype is the more probable explanation for the patients' clinical state. A question is raised, however, whether the Duarte variant may be specifically associated with the development of liver disease in ZZ individuals. (+info)
alpha-1-Anti-trypsin, an inhibitor of renin.
(75/1525)
A naturally occurring competitive inhibitor of pig kidney renin has been identified in human plasma. The inhibitor was shown to be alpha-1 anti-trypsin and the effect in vitro on the renin activity was examined. The slope in the Hill plot is compatible with the assumption of one-site competitive inhibition. Other proteinase inhibitors, such as alpha-2-macroglobulin and C1 inactivator, however, have no inhibitory effect on the renin-angiotensinogen reaction. (+info)
Comparison of the chemical, physical, and survival properties of normal and Z-variant alpha-1-antitrypsins.
(76/1525)
A procedure has been developed for the purification of Z-type alpha-1-antitrypsin (alpha-1-AT) which is rapid, gentle, and results in good yields. From 4 units (750 ml) of fresh human plasma, obtained from two individuals possessing the Pizz phenotype, 53 mg of pure Z-type alpha-1-AT was obtained. The preparation was homogeneous by the criteria of polyacrylamide gel electrophoresis, both in the presence and absence of sodium dodecyl sulfate, and by analytical ultracentrifugation. When compared to pure alpha-1-AT from plasma of individuals possessing the normal PiMM phenotype, the two proteins were indistinguishable with respect to amino acid composition, sedimentation coefficient (s20w of 3.33 for both M and Z), molecular weight (51,000 by sodium dodecyl sulfate gel electrophoresis and 47,000 by sedimentation equilibrium for both M and Z), and trypsin-combining ratio (0.91 for Z and 0.99 for M). The only difference which was observed between the variant forms of alpha-1-AT was in the carbohydrate composition. The Z-type alpha1-AT contains between 20 and 25% less carbohydrate than the M-type alpha-1-AT. Specifically, the Z-type alpha-1-AT is deficient in 1 glucosamine residue, 3 neutral sugar residues (1 mannose and 2 galactose), and 2 sialic acid residues. Although the Z-variant is deficient in sialic acid, its survival time in the serum of a rabbit was not significantly different from that of M-type alpha-1-AT. (+info)
Role of Lys335 in the metastability and function of inhibitory serpins.
(77/1525)
The native form of inhibitory serpins (serine protease inhibitors) is not in the thermodynamically most stable state but in a metastable state, which is critical to inhibitory functions. To understand structural basis and functional roles of the native metastability of inhibitory serpins, we have been characterizing stabilizing mutations of human alpha1-antitrypsin, a prototype inhibitory serpin. One of the sites that has been shown to be critical in stability and inhibitory activity of alpha1-antitrypsin is Lys335. In the present study, detailed roles of this lysine were analyzed by assessing the effects of 13 different amino acid substitutions. Results suggest that size and architect of the side chains at the 335 site determine the metastability of alpha1-antitrypsin. Moreover, factors such as polarity and flexibility of the side chain at this site, in addition to the metastability, seem to be critical for the inhibitory activity. Substitutions of the lysine at equivalent positions in two other inhibitory serpins, human alpha1-antichymotrypsin and human antithrombin III, also increased stability and decreased inhibitory activity toward alpha-chymotrypsin and thrombin, respectively. These results and characteristics of lysine side chain, such as flexibility, polarity, and the energetic cost upon burial, suggest that this lysine is one of the structural designs in regulating metastability and function of inhibitory serpins in general. (+info)
Alpha 1 antitrypsin M1: a new common genetically determined variant.
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A new common variant (M1) of alpha 1 antitrypsin was detected by isoelectric focusing of serum in a pH gradient of 3.5-5.0 in polyacrylamide gels. The variant can be clearly distinguished from the common M type only when alpha 1 antitrypsin M is present in the same serum. It cannot be recognized on starch gel electrophoresis. The gene frequency in a population sample of United States whites was .09. (+info)
Alpha1-antichymotrypsin in rheumatoid arthritis.
(79/1525)
Serum alpha1-antichymotrypsin (alpha1-ACT) of the patient with rheumatoid arthritis was studied by means of single radial immunodiffusion method. There was a significant elevation of the alpha1-ACT concentration in the patients with rheumatoid arthritis, and positive relationships were observed between the concentrations of alpha1-ACT and of other glycoproteins such as alpha1-acid glycoprotein and alpha1-antitrypsin in individual patients, and between C-reactive protein (CRP) rates and the (CRP) rates and the alpha1-ACT concentrations in individual specimens. These facts suggest that alpha1-ACT belongs to a group of acute phase proteins like alpha1-antitrypsin or CRP. An inverse proportional correlation was revealed between alpha1-ACT and fibrinolytic activity. No influences were observed on the alpha1-ACT concentration, activity index or articular index by the oral administration of alpha-chymotrypsin in patients with rheumatoid arthritis. (+info)
Screening for cystic fibrosis by analysis of serum protein in faeces.
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Faecal specimens from 51 infants free of cystic fibrosis (CF) and from 9 infants with the disease were analysed for albumin and alpha1-antitrypsin content. Faeces from infants with no CF had a mean albumin content of less than 0-1 mg/g dry weight and a mean albumin: alpha1-antitrypsin ratio value of less than 0-1. Faeces from infants with CF had, with one exception, an albumin content of more than 2-0 mg/g dry weight and a ratio value greater than 3-0. It was subsequently found that the duodenal aspirate from the child with CF but whose faeces had a low albumin content and ratio value, had tryptic activity though at a much reduced level compared to the activity in aspirates from healthy infants. (+info)