Plasma protein homocysteinylation in uremia

2007 ◽  
Vol 45 (12) ◽  
Author(s):  
Alessandra F. Perna ◽  
Filomena Acanfora ◽  
Maria Grazia Luciano ◽  
Paola Pulzella ◽  
Rosanna Capasso ◽  
...  
Keyword(s):  
Plasma Protein ◽  
Binding Sites ◽  
Free Amino ◽  
Protein S ◽  
Hemodialysis Patients ◽  
Cysteine Residues ◽  
Albumin Binding ◽  
Amino Groups ◽  
Homocysteine Thiolactone

AbstractProtein homocysteinylation is proposed as one of the mechanisms of homocysteine toxicity. It occurs through various means, such as the post-biosynthetic acylation of free amino groups (protein-N-homocysteinylation, mediated by homocysteine thiolactone) and the formation of a covalent -S-S- bond found primarily with cysteine residues (protein-S-homocysteinylation). Both protein modifications are a cause of protein functional derangements. Hemodialysis patients in the majority of cases are hyperhomocysteinemic, if not malnourished. Protein-N-homocysteinylation and protein-S-homocysteinylation are significantly increased in hemodialysis patients compared to controls. Oral folate treatment normalizes protein-N-homocysteinylation levels, while protein-S-homocysteinylation is significantly reduced. Albumin binding experiments after in vitro homocysteinylation show that homocysteinylated albumin is significantly altered at the diazepam, but not at the warfarin and salicilic acid binding sites.Clin Chem Lab Med 2007;45:1678–82.

COMPARATIVE STUDIES OF THE POTENTIATION OF CORTICOTROPHIN ACTIVITY BY SEVERAL INACTIVE DERIVATIVES

1963 ◽  
Vol 42 (2) ◽  
pp. 209-213 ◽  
Author(s):  
Arthur I. Cohen ◽  
Edward H. Frieden
Keyword(s):  
Biological Activity ◽  
Comparative Studies ◽  
Free Amino ◽  
Hormonal Activity ◽  
Amino Groups

ABSTRACT A number of corticotrophin analogues have been prepared, some of which potentiate the biological activity of the untreated hormone in vitro. The free amino groups of corticotrophin appear to be essential not only for hormonal activity, but also for the interaction of the analogues with the tissue corticotrophin inactivating system which is assumed to account for the potentiating effect.

Correction formula for carbamylated haemoglobin in diabetic uraemic patients

2001 ◽  
Vol 38 (2) ◽  
pp. 115-119 ◽  
Author(s):  
A M A Hammouda ◽  
G E Mady
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Free Amino ◽  
Urea Concentration ◽  
Diabetic Patients ◽  
Amino Groups ◽  
Correction Formula ◽  
Significant Difference ◽  
And Control

The measurement of carbamylated haemoglobin is a useful indicator of uraemic state during the preceding few weeks in patients with renal failure. In diabetic uraemic patients with hyperglycaemia, glycation of haemoglobin may interfere with its carbamylation, as both reactions involve the free amino groups of the protein. The aim of this study was to investigate the carbamylation of haemoglobin in the presence of hyperglycaemia. The study included 29 patients with chronic renal failure on regular haemodialysis, 14 diabetic and 15 non-diabetic patients, and 10 healthy controls. We found a significant correlation between the degree of haemoglobin carbamylation and mean blood urea concentration in both uraemic and control subjects. Carbamylation of haemoglobin was higher in both diabetic and non-diabetic chronic renal failure patients, but there were no significant differences between the groups regarding mean blood urea concentration or level of haemoglobin carbamylation. Carbamylated haemoglobin per unit of blood urea concentration was lower in the diabetic patients. Using a correction formula to account for the degree of haemoglobin glycation, there was no longer a significant difference in carbamylation per unit of blood urea concentration. In vitro incubation of red blood cells from six healthy and six diabetic non-uraemic patients in 70mmol/L urea showed a significantly lower carbamylation in the diabetic patients, but there was no significant difference when using corrected carbamylated haemoglobin values. We conclude that glycation of haemoglobin affects its carbamylation and that monitoring of uraemia in a diabetic patient necessitates the use of carbamylated haemoglobin value corrected for the degree of glycation.

scholarly journals THE BINDING OF MYOGLOBIN BY PLASMA PROTEIN

1960 ◽  
Vol 111 (1) ◽  
pp. 65-75 ◽  
Author(s):  
Willoughby Lathem
Keyword(s):  
Plasma Protein ◽  
Binding Sites ◽  
Binding Capacity ◽  
Plasma Hemoglobin ◽  
Renal Threshold ◽  
Dog Plasma ◽  
Beta Globulin ◽  
Maximal Binding

When added to dog plasma in vitro and in vivo, myoglobin was bound to plasma protein in a concentration which, maximally, averaged 21 ± 6 mg. per cent. Electrophoretically, bound myoglobin was separated from free myoglobin and migrated between alpha-2 and beta globulin. The electrophoretic characteristics of protein-bound myoglobin were similar to, although not identical with, those of protein-bound hemoglobin. The maximal binding capacity of plasma for myoglobin was less than for hemoglobin, which averaged 123 mg. per cent. At concentrations below the maximal binding capacity, from 15 to 50 per cent of the myoglobin was in the free, unbound state, differing from hemoglobin which was completely bound at all concentrations below the binding capacity. When myoglobin and hemoglobin were added together to plasma, hemoglobin appeared to interfere with the binding of myoglobin or to replace it at the binding sites. Myoglobin, however, did not appear to interfere with the binding of hemoglobin. These observations suggested that myoglobin and hemoglobin were bound at least in part by the same protein. When myoglobin was given intravenously, free myoglobin was excreted in the urine, whereas protein-bound myoglobin was not excreted. This suggests that protein-binding contributes to or determines the apparent renal threshold to myoglobin.

scholarly journals Albumin-Binding PSMA Radioligands: Impact of Minimal Structural Changes on the Tissue Distribution Profile

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2542 ◽  
Author(s):  
Luisa M. Deberle ◽  
Viviane J. Tschan ◽  
Francesca Borgna ◽  
Fan Sozzi-Guo ◽  
Peter Bernhardt ◽  
...  
Keyword(s):  
Protein Binding ◽  
Tissue Distribution ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Structural Changes ◽  
Albumin Binding ◽  
Distribution Profile ◽  
Tissue Distribution Profile

The concept of using ibuprofen as an albumin-binding entity was recently demonstrated by the development of [177Lu]Lu-Ibu-PSMA-01. In the present study, we designed a novel ibuprofen-containing radioligand (Ibu-PSMA-02) with subtle structural changes regarding the linker entity in order to investigate a potential impact on the in vitro and in vivo properties. Ibu-PSMA-02 was prepared using solid-phase synthesis techniques and labeled with lutetium-177. [177Lu]Lu-Ibu-PSMA-02 was evaluated in vitro with regard to its plasma protein-binding properties, PSMA affinity and uptake into PSMA-expressing PC-3 PIP tumor cells. The tissue distribution profile of [177Lu]Lu-Ibu-PSMA-02 was assessed in tumor-bearing mice and dose estimations were performed. The in vitro characteristics of [177Lu]Lu-Ibu-PSMA-02 were similar to those previously obtained for [177Lu]Lu-Ibu-PSMA-01 with respect to plasma protein-binding, PSMA affinity and tumor cell uptake. The in vivo studies revealed, however, an unprecedentedly high uptake of [177Lu]Lu-Ibu-PSMA-02 in PC-3 PIP tumors, resulting in an increased absorbed tumor dose of 7.7 Gy/MBq as compared to 5.1 Gy/MBq calculated for [177Lu]Lu-Ibu-PSMA-01. As a consequence of the high tumor accumulation, [177Lu]Lu-Ibu-PSMA-02 showed higher tumor-to-background ratios than [177Lu]Lu-Ibu-PSMA-01. This study exemplified that smallest structural changes in the linker entity of PSMA radioligands may have a significant impact on their pharmacokinetic profiles and, thus, may be applied as a means for ligand design optimization.

Fixed Drug Combinations and the Displacement of Bilirubin from Albumin

PEDIATRICS ◽  
1971 ◽  
Vol 48 (1) ◽  
pp. 139-141 ◽  
Author(s):  
D. Schiff ◽  
C. Chan ◽  
L. Stern
Keyword(s):  
Premature Infants ◽  
Binding Sites ◽  
Serum Bilirubin ◽  
Albumin Binding ◽  
Fixed Drug ◽  
The Central Nervous System ◽  
Respiratory Stimulant ◽  
Low Levels

Silverman and associates,1 reported that the use of sulfisoxazole (Gantrisin) in premature infants resulted in the occurrence of kernicterus at low levels of serum bilirubin. Odell2 subsequently demonstrated that sulfisoxazole displaces bilirubin from its albumin binding sites in vitro, thereby making available lipid soluble free bilirubin capable of penetrating the central nervous system. This effect of sulfisoxazole in producing kernicterus has been confirmed experimentally in vivo in rats.3 Odell4 and Khanna, et al.5 have demonstrated a similar but quantitatively even greater bilirubin displacing effect of caffeine sodium benzoate, a drug still recommended by some as a respiratory stimulant for the newborn.

DRUG INTERACTIONS—PART II

PEDIATRICS ◽  
1972 ◽  
Vol 49 (6) ◽  
pp. 916-918
Author(s):  
Leo Stern
Keyword(s):  
Binding Sites ◽  
Unconjugated Bilirubin ◽  
Albumin Binding ◽  
Nonesterified Fatty Acids ◽  
Factors Affecting ◽  
Spectral Curves ◽  
Low Levels ◽  
Bilirubin Binding ◽  
Direct Acting

Unlike its conjugated (direct acting) counterpart, unconjugated (indirect acting) bilirubin is insoluble in water, but highly soluble in lipids. Hence, it tends to diffuse out of plasma into the lipid-rich CNS with resultant kernicterus. This does not occur when unconjugated bilirubin is bound to albumin, as the complex is too large for diffusion. The production of kernicterus thus involves the increase of free, unbound, unconjugated bilirubin in plasma, either by dissociation from its albumin binding sites or by the introduction of one or more anions which compete preferentially for a common or shared site, thus displacing the bilirubin from its albumin bond. FACTORS AFFECTING BINDING Lowering the pH promotes bilirubin-albumin dissociation,1 and acidosis has thus been implicated as a factor in kernicterus occurring at low levels of serum bilirubin.2-5 In addition, competition for bilirubin binding sites is exhibited by a number of endogenously occurring substances as well as exogenously administered agents. Both hematin (increased in hemolytic states) and the nonesterified fatty acids (increased under conditions of both hypothermia6 and hypoglycemia7 are capable of displacing bilirubin from its albumin binding sites. In addition, a number of drugs, among which sulfisoxazole (Gantrisin) is the most widely known in view of both its clinical8 and experimental9 production of kernicterus in this fashion, are capable of causing similar displacement in vitro. Among the techniques employed to demonstrate an increase in free bilirubin is the measurement of displacement of spectral curves.10,7 The technique depends on a difference in absorbance of free (420 to 440 nm) versus bound (460 to 465 nm) bilirubin, with changes in the shapes of the curves as the amounts of free and bound bilirubin are altered.

Small dense LDL is more susceptible to glycation than more buoyant LDL in Type 2 diabetes

2012 ◽  
Vol 124 (5) ◽  
pp. 343-349 ◽  
Author(s):  
Nahla N. Younis ◽  
Handrean Soran ◽  
Philip Pemberton ◽  
Valentine Charlton-Menys ◽  
Mohamed M. Elseweidy ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Free Amino ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Peroxide ◽  
Amino Groups ◽  
Small Dense Ldl ◽  
Ldl Subfractions

Glycation of apoB (apolipoprotein B) of LDL (low-density lipoprotein) increases its atherogenicity. Concentrations of both serum glyc-apoB (glycated apoB) and SD-LDL (small dense LDL) (syn LDL3; D=1.044–1.063 g/ml) are increased in diabetes and are closely correlated. We studied whether SD-LDL is more susceptible to glycation in vitro than more buoyant LDL in statin- and non-statin-treated Type 2 diabetes mellitus. Serum SD-LDL apoB and glyc-apoB on statins was 20±2 (means±S.D.) and 3.6±0.41 compared with 47±3 and 5.89±0.68 mg/dl in those not receiving statins (P<0.001 and <0.01, respectively). There was a dose-dependent increase in glycation on incubation of LDL subfractions with glucose, which was accompanied by an increase in LPO (lipid peroxide) and electrophoretic mobility and a decrease in free amino groups. SD-LDL was more susceptible to these changes than more buoyant LDL. Both SD-LDL and more buoyant LDL from statin-treated patients were less susceptible to glycation. There were fewer free amino groups on LDL subfractions from statin-treated patients, which may contribute to this resistance. In conclusion, greater susceptibility of SD-LDL to glycation is likely to contribute to the raised levels of circulating glyc-apoB in diabetes. Statins are associated with lower levels of both SD-LDL and glyc-apoB.

Activated Protein C Increases Fibrin Clot Lysis by Neutralization of Plasminogen Activator Inhibitor No Evidence for a Cofactor Role of Protein S

1988 ◽  
Vol 60 (02) ◽  
pp. 328-333 ◽  
Author(s):  
N J de Fouw ◽  
Y F de Jong ◽  
F Haverkate ◽  
R M Bertina
Keyword(s):  
Plasminogen Activator ◽  
Protein C ◽  
Blood Platelets ◽  
Plasminogen Activator Inhibitor ◽  
Protein S ◽  
Tissue Type ◽  
Clot Lysis ◽  
Activator Inhibitor ◽  
Pai 1

summaryThe effect of purified human activated protein G (APC) on fibrinolysis was studied using a clot iysis system consisting of purified glu-plasminogen, tissue-type plasminogen activator, plasminogen activator inhibitor (released from endothelial cells or blood platelets), fibrinogen, 125T-fibrinogen and thrombin. All proteins were of human origin.In this system APC could increase fibrinolysis in a dose dependent way, without affecting fibrin formation or fibrin crosslinking. However, this profibrinolytic effect of APC could only be observed when plasminogen activator inhibitor (PAI-l) was present. The effect of APC was completely quenched by pretreatment of APC with anti-protein C IgG or di-isopropylfluorophosphate. Addition of the cofactors of APC:protein S, Ca2+-ions and phospholipid-alone or in combination did not enhance the profibrinolytic effect of APC. These observations indicate that human APC can accelerate in vitro clot lysis by the inactivation of PAI-1 activity. However, the neutralization of PAI-1 by APC is independent of the presence or absence of protein S, phospholipid and Ca2+-ions.

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