Radiochemical method for measuring plasma clearance and urinary excretion of pteroylglutamic acid.

1979 ◽  
Vol 25 (10) ◽  
pp. 1783-1786
Author(s):  
M da Costa ◽  
S P Rothenberg ◽  
Z Rosenberg
Keyword(s):  
Urinary Excretion ◽  
Plasma Clearance ◽  
Normal Subjects ◽  
Serum Folate ◽  
Metabolic Clearance ◽  
Folate Binding Protein ◽  
Radiochemical Method ◽  
Baseline Serum ◽  
Distribution Phase

Abstract A radiochemical procedure is described for specific determination of pteroylglutamate in serum and urine. This method depends on denaturation of methyltetrahydrofolate with peroxide and measurement of the residual folate by a ligand-binding radioassay. The binding determinant for the radioassay is a folate-binding protein, partially purified from chronic myelogenous lekemia cells, that has low affinity for the reduced folates and thus will preferentially measure residual pteroylglutamate rather than any nondenatured residual methyltetrahydrofolate. We used this assay to measure the clearance from plasma and the urinary excretion of pteroylglutamate and a small fraction of serum folate that is stable to this oxidation procedure. The plasma clearance after intravenous injection is characterized by an initial rapid distribution phase followed by a second, slower metabolic phase; after about 2 h all of the administered pteroylglutamate has been cleared from the blood. The peak concentration of total folate in serum 1--2 min after administration of pteroylglutamate exceeded the sum of the endogenous stable and baseline serum folate, indicating that a reduced labile folate was released from the liver and perhaps from other tissues. This reduced folate had a slower metabolic clearance rate and was excreted to some extent in urine. Only 2.3 and 7.9% of the pteroylglutamate administered to two normal subjects was excreted as stable folate.

scholarly journals Clinical and laboratory observations on serum folate-binding protein

Blood ◽  
1975 ◽  
Vol 46 (4) ◽  
pp. 599-609 ◽  
Author(s):  
ER Eichner ◽  
CJ Paine ◽  
VL Dickson ◽  
MD Jr Hargrove
Keyword(s):  
Binding Protein ◽  
Elevated Serum ◽  
Normal Subjects ◽  
Serum Levels ◽  
Serum Folate ◽  
Folate Level ◽  
Folate Binding Protein ◽  
Serum Folate Level ◽  
Relationship Of ◽  
The Relationship

Abstract We studied the effect of serum folate-binding protein (FBP) on folate radioassays and the relationship of the serum level of unsaturated FBP to the serum folate level in various clinical states. Our modification of a heat-extracted radioassay was compared to a whole serum radioassay. Our results confirmed the existence of elevated serum levels of unsaturated FBP in some normal subjects, in some women taking oral contraceptives, and in most patients with uremia. Elevated levels of unsaturated FBP will produce falsely low results in folate radioassay unless the FBP has been destroyed by heat, as was done in the modified radioassay here presented. In normal and uremic subjects, serum folate and unsaturated FBP levels tended to correlate, whereas in patients taking large doses of folic acid the level of unsaturated FBP fell as the level of serum folate rose.

THE URINARY EXCRETION OF AMINOIMIDAZOLECARBOXAMIDE IN THE LESCH-NYHAN SYNDROME

PEDIATRICS ◽  
1970 ◽  
Vol 46 (4) ◽  
pp. 508-512
Author(s):  
David S. Newcombe
Keyword(s):  
Urinary Excretion ◽  
Clinical Evidence ◽  
Megaloblastic Anemia ◽  
Normal Subjects ◽  
Purine Metabolism ◽  
Folate Metabolism ◽  
Serum Folate ◽  
Normal Range ◽  
Purine Synthesis ◽  
The Mean

The urinary excretion of aminoimidazolecarboxamide (AIC), an intermediate in purine synthesis, was studied in five patients with the Lesch-Nyhan syndrome. The mean urinary AIC level for these subjects was 12.03 ± 6.9 mg AIC/mg creatinine as compared to a mean urinary excretion in normal subjects of 1.2 ± 0.6 mg AIC/mg creatinine. None of the patients had clinical evidence of megaloblastic anemia at the time of the study, and their serum folate levels were within the normal range. The increased urinary AIC excretion probably represents a reflection of the deranged purine metabolism in this syndrome and its measurement can be used as a screen for the Lesch-Nyhan syndrome and other disorders of purine and/or folate metabolism.

scholarly journals The Plasma Clearance and Urinary Excretion of Parenterally Administered 58Co B12

Blood ◽  
1956 ◽  
Vol 11 (1) ◽  
pp. 31-43 ◽  
Author(s):  
D. L. MOLLIN ◽  
W. R. PITNEY ◽  
S. J. BAKER ◽  
J. E. BRADLEY
Keyword(s):  
Urinary Excretion ◽  
Vitamin B12 ◽  
Plasma Clearance ◽  
Vitamin B12 Deficiency ◽  
Normal Subjects ◽  
Normal Serum ◽  
Chronic Myelocytic Leukemia ◽  
Intravenous Injections ◽  
Myelocytic Leukemia ◽  
B12 Deficiency

Abstract Intravenous injections of 1.5 µg. of 58Co B12 were given to subjects with normal serum B12 concentrations, to patients with vitamin B12 deficiency and to patients with chronic myelocytic leukemia. The rate of plasma clearance of radioactivity after this dose was slowest in patients with chronic myelocytic leukemia and patients with pernicious anemia in severe relapse. In patients with vitamin B12 deficiency, serum B12 concentrations were estimated microbiologically at frequent intervals after the injection. There was a good correlation between the results obtained by microbiological assay and as calculated from plasma radioactivity. Significant differences were not observed between the urinary excretion of radioactivity by normal subjects and patients with B12 deficiency.

Studies on methylmalonic acid in humans. I. Concentrations in serum and urinary excretion in normal subjects after feeding and during fasting, and after loading with protein, fat, sugar, isoleucine, and valine.

1989 ◽  
Vol 35 (12) ◽  
pp. 2271-2276 ◽  
Author(s):  
K Rasmussen
Keyword(s):  
Urinary Excretion ◽  
Methylmalonic Acid ◽  
Vitamin B12 Deficiency ◽  
Normal Subjects ◽  
Cobalamin Deficiency ◽  
Absolute Amount ◽  
Ambulatory Patients ◽  
B12 Deficiency ◽  
First Time

Abstract Determination of methylmalonic acid (MMA) in serum or urine for evaluation of tissue cobalamin (vitamin B12) deficiency is becoming an important diagnostic procedure. Here I present the first investigation of dietary influence on concentrations of MMA in serum and urine. Everyday meals caused an increase in urinary excretion, whereas the concentration in serum was not increased significantly. It is difficult to prime the accumulation of MMA in normal subjects by stressing the metabolic pathway; after loading subjects with 100 mmol of isoleucine or valine, the absolute amount of MMA excreted increased by only about 3 mumol. Its concentration in serum tended to decrease and its urinary excretion declined after lack of protein intake for more than 15 h. Although a linear relationship was demonstrated, for the first time, between concentrations in serum and urinary excretion, my results indicate that patients with early evidence of cobalamin deficiency and normal subjects may best be differentiated by measurements in serum, especially in the case of nonfasting (i.e., ambulatory) patients.

scholarly journals Clinical and laboratory observations on serum folate-binding protein

Blood ◽  
1975 ◽  
Vol 46 (4) ◽  
pp. 599-609
Author(s):  
ER Eichner ◽  
CJ Paine ◽  
VL Dickson ◽  
MD Jr Hargrove
Keyword(s):  
Binding Protein ◽  
Elevated Serum ◽  
Normal Subjects ◽  
Serum Levels ◽  
Serum Folate ◽  
Folate Level ◽  
Folate Binding Protein ◽  
Serum Folate Level ◽  
Relationship Of ◽  
The Relationship

We studied the effect of serum folate-binding protein (FBP) on folate radioassays and the relationship of the serum level of unsaturated FBP to the serum folate level in various clinical states. Our modification of a heat-extracted radioassay was compared to a whole serum radioassay. Our results confirmed the existence of elevated serum levels of unsaturated FBP in some normal subjects, in some women taking oral contraceptives, and in most patients with uremia. Elevated levels of unsaturated FBP will produce falsely low results in folate radioassay unless the FBP has been destroyed by heat, as was done in the modified radioassay here presented. In normal and uremic subjects, serum folate and unsaturated FBP levels tended to correlate, whereas in patients taking large doses of folic acid the level of unsaturated FBP fell as the level of serum folate rose.

scholarly journals The Determination of Erythrocyte Folate Concentration Using a Two-Phase Ligand-binding Radioassay

Blood ◽  
1974 ◽  
Vol 43 (3) ◽  
pp. 437-443 ◽  
Author(s):  
Sheldon P. Rothenberg ◽  
Maria da Costa ◽  
John Lawson ◽  
Zoltan Rosenberg
Keyword(s):  
Ligand Binding ◽  
Lactobacillus Casei ◽  
Normal Subjects ◽  
Normal Serum ◽  
Serum Folate ◽  
Two Phase ◽  
Folate Concentration ◽  
Erythrocyte Folate ◽  
The Mean

Abstract The concentration of folate in erythrocytes was determined using a two-phase ligand-binding radioassay procedure described previously for measuring serum folate. The mean (± SD) folate concentration in erythrocytes of 20 normal subjects was 210 ± 57 ng/ml. In 12 patients clinically folate deficient who had normal serum B12 concentration, the mean (± SD) erythrocyte folate was 71 ± 39 ng/ml. Incubation of the lysed erythrocytes for 2 hr prior to boiling increased the radioassayable folate. The radioassayable folate decreased rapidly if the whole blood was stored at 4°C without ascorbate. Extracts of blood prepared with ascorbate could be stored at -20°C for several days. The radioassayable concentration of erythrocyte folate was similar to the values obtained using Lactobacillus casei when the concentration was 200 ng/ ml or less. With values higher by L. casei, the radioassayable folate was significantly lower even though the normal and folate-deficient groups were distinctly separated. This radioassay provides a rapid and reliable method of measuring erythrocyte folate, a parameter which reflects folate stores more reliably than serum folate concentration.

scholarly journals Interrelationship of Rheumatoid Arthritis, Folic Acid, and Aspirin

Blood ◽  
1971 ◽  
Vol 38 (4) ◽  
pp. 405-416 ◽  
Author(s):  
HARVEY J. ALTER ◽  
NATHAN J. ZVAIFLER ◽  
CHARLES E. RATH
Keyword(s):  
Rheumatoid Arthritis ◽  
Folic Acid ◽  
Plasma Clearance ◽  
Normal Subjects ◽  
Serum Levels ◽  
Serum Folate ◽  
Pteroylglutamic Acid ◽  
Apparent Equilibrium ◽  
Low Serum

Abstract Decreased serum folate (FA) levels were detected in 71% of 51 patients with rheumatoid arthritis (RA). Of 11 patients studied more intensively, only one fulfilled the usual hematologic criteria for FA deficiency. All, however, demonstrated an abnormally rapid plasma clearance of tritium-labeled pteroylglutamic acid (3HPGA). "Binding" of 3HPGA was evaluated by dialysis to apparent equilibrium and found to be significantly reduced in the sera of patients with RA. Common to all these patients was the ingestion of aspirin (ASA). Four RA patients not taking ASA had normal 3HPGA "binding". The 3HPGA "binding" of RA sera decreased as these patients were given increased ASA dosage and vice versa. The in vitro addition of ASA to normal sera reduced "binding" to the level detected in RA sera. Progressive increases in ASA resulted in progressive decreases in "binding". Aspirin given to three normal subjects reduced 3HPGA "binding" in all and serum FA in two. Precedents for ASA-induced structural change in binding proteins and for the relation between decreased binding and lowered serum levels are discussed. It is suggested that the low serum FA concentration and rapid plasma clearance of 3HPGA in RA might reflect ASA-induced alterations of FA binding, resulting in a redistribution rather than deficiency of this vitamin.

Plasma kinetics and urinary excretion of exogenous human and salmon calcitonin in man.

1979 ◽  
Vol 236 (1) ◽  
pp. E15 ◽  
Author(s):  
R Huwyler ◽  
W Born ◽  
E E Ohnhaus ◽  
J A Fischer
Keyword(s):  
Urinary Excretion ◽  
Salmon Calcitonin ◽  
Gel Filtration ◽  
Normal Subjects ◽  
Metabolic Clearance ◽  
Clearance Rates ◽  
Plasma Kinetics ◽  
The Difference

The metabolism and the urinary excretion of synthetic human and salmon calcitonin-(1--32) [hCT-(1--32), sCT-(1--32)] administered by constant infusions for 240 min were investigated in eight normal subjects. On gel filtration of plasma obtained during the infusions mainly intact hCT-(1--32) and sCT-(1--32) were recognized with homologous radioimmunoassay systems. During constant infusions to equilibrium of 0.04 mg hCT-(1--32) and sCT-(1--32), the metabolic clearance rates (MCR) amounted to 8.4 +/- 1.1 and 3.1 +/- 0.1 ml/kg per min, respectively (P less than 0.01). When hCT-(1--32) was infused at rates of 1 and 4 mg/240 min, the MCR were lower than with 0.04 mg hCT-(1--32), but still higher than with 0.04 mg sCT-(1--32). The half-lives of disappearance of hCT-(1--32) were faster compared to sCT-(1--32), but the difference was not statistically significant. The urinary clearance of hCT-(1--32) determined during the 1 and 4 mg/240 min infusions of hCT-(1--32), as well as of sCT-(1--32) determined during the 0.04-mg infusions of sCT-(1--32) was about 0.1% of the MCR. The half-lives of disappearance of hCT- and sCT-(1--32) incubated in vitro in plasma and urine ranged from 17 to more than 72 h, and the degradation did not affect our calculations of the metabolic breakdown of exogenous CT in vivo.

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