Showing papers on "Serum albumin published in 1977"

Pathogenesis of alcohol-induced accumulation of protein in the liver.

Abstract: Alcohol feeding to rats produced hepatomegaly, associated with enlargement of the hepatocytes. The increase in liver dry weight was accounted for not only by fat but also by protein accumulation, primarily in microsomes and cytosol, with a selective increase in export proteins: concentrations of both immunoreactive albumin and transferrin were augmented in liver microsomes and cytosol of ethanol-fed rats. To investigate the mechanism of this protein accumulation, [14C]leucine was injected intravenously and its incorporation into both liver and serum proteins was measured after various time intervals. Rates of synthesis and export were assessed from protein labeling and specific activities of leucyl-tRNA. Synthesis of liver protein and proalbumin were enhanced by chronic ethanol feeding, but this was not associated with a corresponding rise in serum albumin output. Actually, there was a significant retention of the label in liver albumin and transferrin with delayed appearance in the serum of ethanol-fed rats. This indicated that, regardless of the changes in synthesis, the export of protein from the liver into the plasma was impaired. This alteration in export was associated with a decreased amount of polymerized tubulin in the liver of ethanol-treated animals. Thus, both enhanced protein synthesis and defective export contribute to the ethanol-induced accumulation of liver protein, and the decrease in liver microtubules represents a possible site for impairment of protein export.

Effect of albumin binding and amino acid competition on tryptophan uptake into brain.

Abstract: — In the present study we examine the influence of pH, palmitate, and neutral amino acids on the passage of tryptophan from blood into brain during a single capillary pass, and on the partitioning of tryptophan between free and albumin-bound forms. The results show that a considerable fraction of albumin-bound tryptophan is stripped from albumin sites during passage, that uptake is concentration-dependent, and that amino acid competition for carrier sites is quantitatively the most important factor in regulating tryptophan uptake into brain. The interaction between tryptophan concentration, tryptophan binding, and competing amino acids is of considerable influence on brain serotonin biosynthesis.

Some aspects of the structure and conformational properties of serum albumin

Abstract: Publisher Summary This chapter presents the structure and conformational properties of serum albumin. The functional properties of serum albumin, other than from its possibly coincidental importance in the maintenance of proper osmotic balance, relate to its unusual and versatile liganding ability. Well-known are its ability to bind such diversified substances as fatty acids, bilirubin, tryptophan, various metal ions, most anions, some hormones, and numerous drugs. Undoubtedly serum albumin serves a role in transporting such substances, but also it may serve an equally vital role in buffering or regulating the concentrations of various low molecular weight substances. Two general aspects of serum albumin structure and function are considered: (1) the heterogeneity and microheterogeneity of the protein and (2) the conformational transformations that the protein undergoes in solution.

Serum albumin: recent progress in the understanding of its structure and biosynthesis.

Abstract: Major discoveries have been made in the past few years on the structure and mode of biosynthesis of serum albumin. The complete amino acid sequence of this protein has been determined, and its covalent structure shown to be a single peptide chain grouped into a series of nine disulfide-bonded loops. These loops appear to associate into three similar domains. By study of isolated fragments of the molecule it can be demonstrated that the binding of billirubin and the primary binding of long-chain fatty acids are functions of separate domains. The biosynthesis of albumin has been found to involve a precursor form, termed "proalbumin", in which a basic hexapeptide is attached to the amino end of the chain. Similar precursor forms are now known to have a role in the formation of other secreted proteins, but in the case of albumin the purpose of the additional peptide is not clear. Clinical methodology for albumin assay has advanced but little despite--or perhaps in part because of--the increasing use of automation. Hope for improvement is foreseen in the advent of immunochemical procedures and in a better understanding of the specificity of dye-binding reactions.

Relationship among the concentrations of serum lipoproteins and changes in their chemical composition in patients with untreated nephrotic syndrome

Abstract: . The quantitative and qualitative changes of serum lipoproteins have been studied in twelve patients with untreated uncomplicated nephrotic syndrome. The lipoprotein disorders found in these patients were characterized by an elevation of VLDL (d < 1.006 g ml-1), LDL (d 1.006–1.019 g ml-1) and LDL2 (d 1.019–1.063 g ml-1) and a diminution of HDL2 (d 1.063–1.125 g ml-1). These changes were strictly correlated with the concentration of serum albumin and were more pronounced in the patients with serum albumin < 20 g l-1. The study of the relationship among the concentrations of the various lipoprotein classes indicated that (i) the levels of VLDL and LDL1 were reciprocally related to that of the high density lipoproteins and (ii) the level of LDL2 rose with the moderately increased VLDL and LDL1 but at the high concentrations of VLDL and LDL1 observed in the severe nephrotic syndrome it did not show any further increase, suggesting a defect in the conversion of VLDL to LDL2. The nephrotic syndrome was associated with marked changes in the composition of all lipoprotein fractions which were found to contain more phospholipid but less protein than normal. Major changes in composition were observed in VLDL and LDL1 which were rich in esterified cholesterol and phopholipids and had an esterified cholesterol: triglyceride molar ratio (CE/TG) higher than the corresponding fractions of the control subjects. Furthermore, CE/TG ratio in these fractions increased as their serum concentration increased. These observations indicate that in severe, untreated uncomplicated nephrotic syndrome there is a progressive accumulation of d < 1.019 g ml-1 lipoproteins rich in esterified cholesterol. Chemically these resemble VLDL and chylomicron remnants and are possibly related to some defect in the conversion of VLDL to LDL2.

Albumin medicament carrier system

Abstract: Solid serum albumin spherules having 5 to 30 percent by weight of an organic medicament homogeneously entrapped therein are disclosed. These spherules are especially suited for intravascular injection into the body wherein the drug is released from the spherule in a biphasic manner having an initial fast release phase followed by a slow release phase.

Serum albumin: amino acid sequence

Abstract: Publisher Summary This chapter focuses on amino acid sequence. It reviews the primary structures of bovine and human serum albumin. Elucidation of the amino acid sequence of serum albumin has led to much greater insights into the structure, function, and evolution of this protein than was anticipated. The application of the three-dimensional models of albumin are supported by a variety of evidence, namely, helix content, properties of fragments, reactive groups, binding properties, protein dimensions, and similarity to the G-H region of globin structure. The models are specific enough that details can be tested and refined by further experiments, such as affinity labeling, crosslinking, and further preparation and analysis of properties of fragments.

Plasma protein synthesis by isolated rat hepatocytes.

Abstract: A system of preparation of rat hepatocytes with extended viability has been developed to study the role of hormones and other plasma components upon secretory protein synthesis. Hepatocytes maintained in minimal essential medium reduced the levels of all amino acids in the medium except the slowly catabolized amino acids leucine, isoleucine, and valine, which steadily increase as the result of catabolism of liver protein. Although the liver cells catabolize 10-15% of their own protein during a 20-h incubation, the cells continue to secrete protein in a linear fashion throughout the period. The effects of insulin, cortisol, and epinephrine on general protein synthesis, and specifically on fibrinogen and albumin synthesis, have been tested on cells from both normal rats and adrenalectomized rats. Cells from normal animals show preinduction of tyrosine amino transferase (TAT), having at the time of isolation a high level of enzyme which shows only an increase of approximately 60% upon incubation with cortisol. In contrast, cells from adrenalectomized animals initially have a low level of enzyme which increases fourfold over a period of 9 h. The effects of both epinephrine and cortisol on protein synthesis are also much larger in cells from adrenalectomized animals. After a delay of several hours, cortisol increases fibrinogen synthesis sharply, so that at the end of the 20-h incubation, cells treated with hormone have secreted nearly 2.5 times as much fibrinogen as control cells. The effect is specific; cortisol stimulates neither albumin secretion nor intracellular protein synthesis. The combination of cortisol and epinephrine strongly depresses albumin synthesis in both types of cells. Insulin enhances albumin and general protein synthesis but has little effect on fibrinogen synthesis.

Cell-free synthesis of the fourth component of guinea pig complement (C4): identification of a precursor of serum C4 (pro-C4)

Abstract: Polysomes (S-20) from homogenates of guinea pig liver synthesized serum albumin and a precursor of the fourth component of guinea pig complement (C4) in vitro. The C4 precursor (pro-C4) accounted for approximately 0.2% and albumin 4% of the radiolabeled protein precipitable by trichloroacetic acid and not bound to polysomes. Pro-C4 is a single polypeptide chain (molecular weight 200,000) which is then converted to C4, a three-chain (molecular weights 95,000, 78,000 and 31,000) structure linked by interchain disulfide bridges. Pro-C4 was also detected intracellularly in short-term tissue cultures of guinea pig liver. C4 was found in the medium harvested from these cultures.

Decreased parathyroid function in hyperthyroidism: interrelationships between serum parathyroid hormone, calcium-phosphorus metabolism and thyroid function.

Abstract: Serum immunoreactive parathyroid hormone (S-iPTH) was measured together with serum and urinary calcium and phosphorus in 45 hyperthyroid patients in order to assess parathyroid fe of hyperthyroidism. The prevalence of hypercalcaemia was 51.1% using serum calcium values corrected for individual variations in serum albumin concentration compared to 15.6% using the uncorrected calcium values. S-iPTH was decreased and inversely correlated to serum calcium values. S-iPTH was decreased and inversely correlated to serum calcium (corrected). Subnormal levels of S-iPTH were found in 28.9% of the patients. The urinary excretion of calcium and phosphorus was increased and positively correlated to the degree of hyperthyroidism. The tubular reabsorption of calcium (TRCa%) was decreased, positively correlated to S-iPTH and inversely correlated to serum calcium. Increased mobilisation of bone mineral in hyperthyroidism is suggested mainly to be responsible for the elevated serarathyroid function.

Effects of Fatty Acids on Two Specific Drug Binding Sites on Human Serum Albumin

Abstract: Two distinct binding sites, I and II, for anionic drugs on human serum albumin have previously been demonstrated using fluorescent probe techniques. 5-Dimethylaminonaphthalene-1-sulfonamide (DNSA) and dansylsarcosine are specific fluorescent probes for sites I and II, respectively. The addition of fatty acids results in differing effects at the two binding sites, and the specificity of site II is lost. The order of potency of various fatty acids in causing these changes is oleic > stearic > linoleic [unknown] palmitic, and this is the same as the order of association constants for these fatty acids. It is concluded that chain length and degree of unsaturation determine both binding affinity and the extent to which the fatty acids induce configurational adaptations in the albumin molecule. Furthermore, studies with varying ratios of oleic acid to albumin suggest that the conformational changes induced in the protein are different for each molecule of oleic acid added. Addition of oleic acid at a 3:1 molar ratio with albumin significantly increased the binding of warfarin and DNSA to site I.

25-hydroxyvitamin D and its binding protein in maternal and cord serum

Abstract: Serum calcium, phosphorus, albumin, total protein, 25-hydroxyvitamin D (25OHD) and the vitamin D-binding protein (DBP) were measured in 30 cord sera and in 30 sera obtained simultaneously from their respective mothers. The maternal serum concentration of 25OHD (14.0 +/- 6.9 microgram/l, mean +/- SD) and of DBP (574 +/- 72 mg/l) were significantly higher than the respective cord serum concentration (8.0 +/- 4.4 microgram/l and 268 +/- 39 mg/l). The calculated concentration of "free 25OHD," however, was slightly but significantly higher in cord serum (0.44 +/- 0.24 ng/l) than in maternal serum (0.34 +/- 0.18 ng/l). Serum calcium and phoshporus were lower in maternal than in cord serum. A highly significant positive correlation was found between maternal and cord serum concentration of DBP (r = 0.59), total 25OHD (r = 0.79), "free 25OHD" (r = 0.86) and phosphorus (r = 0.73). These data indicate that the concentration of DBP is important for the evaluation of the placental transfer of 25OHD. Indeed, the concentration of "free 25OHD" is slightly higher in cord serum than in maternal serum, despite the maternal-to-fetal gradient of total 25OHD. The low fetal concentration of DBP is also unfavorable for the fetal storage of 25OHD during intrauterine life.

Progressive changes in individual milk protein concentrations associated with high somatic cell counts.

Abstract: Progressive changes in the concentrations of milk protein components were followed after infusions of Streptococcus agalactiae or bacterial endotoxin into different quarters of individual cows. Both types of infusion produced similar increases in somatic cell count and resulted in similar changes in milk proteins, although the effects of the endotoxin infusion lasted for a shorter length of time. The treatments had little effect on α-lactalbumin and β-lactoglobin concentrations, but serum albumin and immunoglobulin (Ig) concentrations increased markedly. The greatest effect on serum albumin was after the endotoxin infusion and on Ig after the Str. agalactiae infusion. Changes in the individual globulins indicated that passive transfer of blood proteins to milk could not account for the observed increases in IgM and IgA. α s1 -Casein and β-casein concentrations were reduced and inversely related to somatic cell count during the immediate post-infusion period, and this was accompanied by an increase in para-κ-casein. Para-κ-casein was not detected in pre-infusion or post-recovery milk samples. The decrease in β-casein was greater than that of α s1 -casein. Casein concentrations returned to pre-infusion levels 2 d and 5 d after the endotoxin and Str. agalactiae infusions respectively. The possibility that proteolytic enzymes are partly responsible for the changes in casein concentration is discussed.

Immunochemistry of Proteins

Abstract: 1 Effector Sites on Antibodies.- I. Introduction.- II. General Structure and Organization of Immunoglobulins.- A. General Structure.- B. Domain Theory.- C. Fragmentation of Immunoglobulins.- D. Shape of Immunoglobulins.- III. Effector Functions Mediated by Antibodies.- A. Protein-Binding Properties of Immunoglobulins.- B. Cell-Binding Properties of Immunoglobulins.- IV. Conclusions.- V. References.- 2 Antigenic Features of Immunoglobulins.- I. Introduction.- II. Basic Features of Antigenic Determinants.- III. Constant Region Determinants.- A. Heavy-Chain Isotypic Determinants.- B. Light-Chain Isotypic Determinants.- C. Nonisotypic Light-Chain Constant Region.- D. Determinants.- IV. Allotypic Markers.- A. Allotypes of Human Immunoglobulins.- B. Allotypes of Rabbit Immunoglobulins.- V. Variable Region Determinants.- A. Light-Chain Variable Region Determinants.- B. Heavy-Chain Variable Region Determinants.- VI. Interspecies Antigenic Determinants.- VII. Other Significant Immunoglobulin Determinants.- A. Rheumatoid Factor Determinants.- B. J-Chain Determinants.- C. Secretory Piece Determinants.- VIII. Summary and Conclusions.- IX. References.- 3 Combining Regions of Antibodies.- I. Background.- A. Introduction.- B. Antibody Populations.- C. How Many Antibodies and Antigens Exist?.- D. Combining Region Variability.- II. Structural Studies.- A. Primary Structure.- B. Affinity Labeling.- C. Polymeric Ligand Probes of the Combining Region: How Large Is It?.- D. Electron Microscopic Studies of the Antigen-Antibody Complexes.- E. X-Ray Crystallography.- F. Conformational Changes Secondary to Antigen Binding.- III. Structure-Function Relationships.- A. Introduction.- B. Relationships between Primary Structure and Binding Specificity.- C. Variable Region Groups and Subgroups.- D. Hapten Contact and Hypervariable Regions.- E. Conservation of Variable Regions.- F. Kinetics of Antigen Binding.- G. Homogeneous and Heterogeneous Binding.- IV. Biological Significance of Antigen Binding.- A. Polyfunctional Antibody-Combining Regions.- B. Specificity of Immune Sera.- C. Epidemiological Considerations.- D. Maturation of Antibody Specificity.- V. Summary.- VI. References.- 4 Biochemistry and Biological Reactions of Complement Proteins.- I. Introduction.- II. Classical Pathway.- A. Complement Nomenclature.- B. C1 Subcomponent Composition.- C. Other Proteins of the Classical Pathway.- III. Alternative Pathway.- A. Introduction.- B. Nomenclature.- C. Proteins of the Alternative Pathway.- IV. The Complement Attack Mechanism.- A. Proteins of the C Attack Mechanism.- B. Activation of the C Attack Mechanism.- C. Interactions of the C Attack Proteins.- D. Interaction between the C Attack Proteins and Membranes.- E. Control of the Complement Attack Mechanism.- V. Conclusion.- VI. Addendum.- VII. References.- 5 Immunochemistry of Bovine Serum Albumin.- I. Introduction.- II. Structure of Bovine Serum Albumin.- A. Conformational Transitions of Albumin.- B. Molecular Organization of Bovine Serum Albumin.- C. Microheterogeneity.- D. Fragmentation of Bovine Serum Albumin by Proteolytic Enzymes.- E. Conformational Studies on Fragments from Bovine Serum Albumin and on Modified Albumin.- III. Immunochemistry of Chemical Derivatives of Bovine Serum Albumin.- A. Modification of the Cystine Residues in Bovine Serum Albumin.- B. Modification of Amino Groups.- C. Modification of Carboxylic Groups of Bovine Serum Albumin.- IV. Immunochemistry of Fragments of Bovine Serum Albumin.- A. Cleavage by Chymotrypsin.- B. Cleavage by Cyanogen Bromide.- C. Cleavage of Citraconyl-BSA by Trypsin.- D. Cleavage by Trypsin.- E. Immunochemical Cross-Reaction of Fragments 11-193 and 377-571.- F. Immunochemistry of Chemical Derivatives of Peptide Fragments.- V. Immunochemical Studies on Human Serum Albumin.- A. Effect of Chemical Modification on Immunochemical Reactivity of Human Serum Albumin.- B. Immunochemistry of Fragments from Human Serum Albumin.- VI. Structural and Immunochemical Studies on Serum Albumin from Various Species.- A. Structural Studies.- B. Immunochemical Cross-Reactivity of Serum Albumins.- C. Immunochemical Reactivity of Fragments of Albumins.- VII. Conclusion.- VIII. References.- Author Index.

Differences in the binding of drugs to plasma proteins from newborn and adult man. II

Abstract: The binding of certain drugs to isolated fractions of plasma proteins obtained from newborn and adult man has been studied by equilibrium dialysis. For thiopental, desipramine, nitrofurantoin, sulfamethoxydiazine, meticillin and salicylic acid no difference was found between binding to the albumin fraction from newborns and adults. However, for thiopental, desipramine and promethazine binding to the globulin fraction was smaller in the newborns than in adults. Addition of bilirubin to the albumin fraction decreased the binding of nitrofurantoin, sulfamethoxydiazine and meticillin. No difference in the binding of meticillin to the albumin or globulin fractions from newborns and adults was found. The binding decreased, however, if both fractions were combined. Four mechanisms to explain the difference in binding between newborns and adults are discussed: (1) Displacement of drugs by bilirubin, (2) different binding properties of cord and adult albumin, (3) different properties of the globulins and (4) interaction of albumin with globulins in the newborn.

Rat liver preproalbumin: in vitro synthesis and partial amino acid sequence.

Abstract: Rat liver poly(A)-containing RNA greatly stimulated incorporation of radioactive amino acids into protein when added to a wheat germ in vitro translation system. Approximately 7% of the labeled synthetic product was precipitated following indirect immunoprecipitation with antisera to rat serum albumin. Analysis of this material, and of the cyanogen bromide fragments derived from it, by sodium dodecyl sulfate/polyacrylamide gel electrophoresis revealed that it contained an NH2-terminal extension of about 2500 daltons when compared to rat serum albumin. Automated sequence determination of purified cell-free product labeled with various radioactive amino acids revealed the presence of 18 additional amino acids NH2-terminal to the sequence of rat proalbumin. The partial sequence of this extension was found to be: Met-X-X-X-X-Phe-Leu-Leu-Leu-Leu-Phe-X-X-X-X-X-Phe-X-proalbumin. On the basis of this evidence, the immunoprecipitable cell-free product was designated preproalbumin.

Stimulation by immune complexes of mucus release from goblet cells of the rat small intestine

Abstract: Immune complexes (bovine serum albumin with rat antibodies to bovine serum albumin) formed in twofold antibody excess were injected into the duodenum of normal rats. In comparison to controls injected with antigen only, there was a marked increase in the percentage of disrupted goblet cells (an index of mucus release) in segments from the intestine of rats exposed for 3 hours to immune complexes in vivo. Similarly, there was a significant increase in 35S-labeled mucus recovered by filtration of intestinal wash, rinse, and mucosal homogenate fluids from rats exposed to immune complexes compared to those from rats exposed to bovine serum albumin or purified rat antiserum to bovine serum albumin alone. These findings suggest that certain immune complexes can stimulate mucus release from intact rat small intestine; enhanced mucus release may have a role in clearing the surface of complexes.

Thyroid function and thyroid regulation in euthyroid men with chronic liver disease: evidence of multiple abnormalities.

Abstract: SUMMARY Total and free serum thyroxine (T4) and triiodothyronine (T3), basal serum thyrotrophin (TSH) and the serum TSH response to a standard intravenous dose of thyrotrophin releasing hormone (TRH) have been measured in fifteen men with liver cirrhosis and in eight alcoholic men with fatty liver change. All the patients studied were clinically euthyroid. In cirrhotics, total T4 and free T4 (FT4) concentrations were normal as were free T3 (FT3) concentrations but total T3 concentrations were significantly reduced and basal TSH concentrations were significantly higher than normal. Alcoholics with fatty liver change had normal basal TSH concentrations and normal total and free thyroid hormone concentrations apart from reduced FT4. Correlation of thyroid function tests with liver function (serum albumin concentration) showed significant positive correlations for serum albumin with both total T3 and FT3 and significant negative correlations with both FT4 and basal TSH. Nine of fifteen cirrhotics had an abnormal serum TSH response to TRH, the commonest abnormal pattern being a delayed response (seven patients). Three of eight alcoholics with fatty liver change also had an abnormal TSH response to TRH. These findings not only show complex disturbances in hypothalamic-pituitary-thyroid relationships in chronic liver disease but also provide indirect evidence of reduced extra-thyroidal conversion of T4 to T3.