scholarly journals Comparative studies on intrinsic factor and cobalophilin in different parts of the gastrointestinal tract of the pig

1978 ◽  
Vol 173 (3) ◽  
pp. 705-712 ◽  
Author(s):  
George Marcoullis ◽  
Hannele Merivuori ◽  
Ralph Gräsbeck
Keyword(s):  
Gastrointestinal Tract ◽  
Vitamin B12 ◽  
Gastric Juice ◽  
Neutral Type ◽  
Intrinsic Factor ◽  
Molecular Forms ◽  
Intrinsic Factors ◽  
Intestinal Juice ◽  
Pyloric Mucosa ◽  
Significant Difference

The vitamin B12 binders in the pig pyloric mucosa gastric and intestinal juice from the upper gastrointestinal tract were fractionated into only two molecular forms, classified as intrinsic factor and cobalophilin. The unsaturated vitamin B12-binding power due to cobalophilin was lower in the intestinal than in the gastric juice. Electrofocusing revealed that intrinsic factor and cobalophilin in the intestinal juice contained more of the ‘neutral’-type isoproteins, and the suggestion is made that this is due to enzyme activity. The gastric-juice intrinsic factor contained more acidic isoproteins, which supports the hypothesis that carbohydrate is added on to the polypeptide chain of this protein before it is secreted into gastric juice. The gastric- and intestinal-juice cobalophilins, studied also by electrofocusing, differed from that of pyloric mucosa and they appeared to be of salivary origin. With regard to molecular dimensions there was no significant difference between the intrinsic factors and cobalophilins from all sources studied. All cobalophilins had molecular weights by the formula of Svedberg of approx. 92500, Stokes radii of 4.62nm and sedimentation coefficients of 5.15S. The corresponding values for the intrinsic factors were 63600, 3.57nm and 4.38S. In addition, the intrinsic factors exhibited similar avidities for binding to the solubilized ileal intrinsic-factor receptor. Also the intrinsic factors and cobalophilins, irrespective of their source, bound to the analogous specific xenoantibodies with the same avidity. The present results demonstrate that intrinsic factor remains practically unaltered during its passage through the proximal intestine and render unlikely the speculations made about the presence of an endogenous binder for intrinsic factor as well as the existence of a ‘pancreatic intrinsic factor’. In addition, they are compatible with the theory that the interference by undegraded cobalophilin may be the reason for the abnormal vitamin B12 absorption observed in patients with pancreatic insufficiency.

scholarly journals On the Nature of Castle’s Hemopoietic Factor

Blood ◽  
1951 ◽  
Vol 6 (12) ◽  
pp. 1234-1239 ◽  
Author(s):  
SHEILA T. CALLENDER ◽  
L. G. LAJTHA
Keyword(s):  
Vitamin B12 ◽  
Gastric Juice ◽  
Intrinsic Factor ◽  
Normal Serum ◽  
Relationship Of ◽  
The Relationship

Abstract 1. Normal gastric juice (intrinsic factor) and vitamin B12 together form a thermolabile hemopoietic factor which ripens megaloblasts in vitro, both gastric juice and B12 alone being inactive. 2. The hemopoietic factor in normal serum which ripens megaloblasts in vitro also appears to be thermolabile, heating to 56 C. for 2 hours destroying some of its activity. 3. The relationship of these factors is discussed and an extra-gastric as well as a gastric source of intrinsic factor is postulated.

scholarly journals Separation of Vitamin B12-Binding Proteins of Serum, Gastric Juice and Saliva by Rapid DEAE Cellulose Chromatography

Blood ◽  
1967 ◽  
Vol 29 (4) ◽  
pp. 501-516 ◽  
Author(s):  
FRANCOIS P. RETIEF ◽  
CHESTER W. GOTTLIEB ◽  
SHAUL KOCHWA ◽  
PETER W. PRATT ◽  
VICTOR HERBERT
Keyword(s):  
Vitamin B12 ◽  
Pernicious Anemia ◽  
Gastric Juice ◽  
Intrinsic Factor ◽  
Deae Cellulose ◽  
The Other ◽  
Main Peak ◽  
Binding Material ◽  
Beta Globulin ◽  
Two Peaks

Abstract A method of DEAE cellulose chromatography is described whereby the main vitamin B12 binders in serum, gastric juice and saliva may be separated into two distinct fractions, one containing alpha-globulin binder and the other containing beta-globulin binder, in less than 2 hours. Typical elution patterns of alpha-globulin and beta-globulin B12 binders from normal (⅘ beta; ⅕ alpha), pernicious anemia (⅔ beta; ⅓ alpha), and chronic myeloid leukemia (CML) (¾ alpha) sera are presented. Chromatography of normal gastric juice produced two peaks of B12-binding material, one containing all the intrinsic factor (IF) B12 binder (as well as some non-IF binder), and the other consisting almost exclusively of non-IF B12 binders. Pernicious anemia gastric juice also produced two peaks, but IF was absent. Saliva had one main peak of B12-binding material which seemed to correspond to the non-IF binder of normal gastric juices; both of these eluted with the alpha-globulin fraction.

Occurrence in Gastric Juice of Antibody to a Complex of Intrinsic Factor and Vitamin B12

1966 ◽  
Vol 275 (10) ◽  
pp. 528-531 ◽  
Author(s):  
Stanley G. Schade ◽  
Patricia Feick ◽  
Mary Muckerheide ◽  
Robert F. Schilling
Keyword(s):  
Vitamin B12 ◽  
Gastric Juice ◽  
Intrinsic Factor

scholarly journals A Case of Juvenile Pernicious Anemia: Study of the Effects of Folic Acid and Vitamin B12

Blood ◽  
1961 ◽  
Vol 17 (5) ◽  
pp. 618-631 ◽  
Author(s):  
DAVID H. CLEMENT ◽  
CHARLES A. NICHOL ◽  
ARNOLD D. WELCH
Keyword(s):  
Folic Acid ◽  
Vitamin B12 ◽  
Pernicious Anemia ◽  
Gastric Juice ◽  
Intrinsic Factor ◽  
Later Life ◽  
Free Hydrochloric Acid ◽  
Specific Therapy ◽  
Sequence Of Events ◽  
Almost All

Abstract Observations on a 4-year-old boy with Addisonian pernicious anemia have been presented. Noteworthy clinical features included the onset of glossitis at the age of 4 months, followed by anemia severe enough to require hospitalization at the age of 1 year. Relapse occurred in the absence of specific therapy with vitamin B12 and was completely unaffected by the administration of folic acid. Studies with radioactive vitamin B12 demonstrated that almost all of the compound administered by mouth was unabsorbed and was recovered in the stools. When the vitamin was given simultaneously with a concentrate of intrinsic factor, however, approximately 70 per cent was absorbed. Furthermore, the child’s gastric juice, when mixed with radioactive vitamin B12 and fed to an adult with pernicious anemia in relapse, failed to enhance the latter’s absorption of the vitamin. The failure of our patient to absorb the vitamin alone, but his ability to do so when it was administered with intrinsic factor concentrate, was also confirmed by the "Schilling test," in which a proportion of the absorbed radioactive vitamin was "flushed" into the urine by parenteral injection of one milligram of conventional vitamin B12. Of special interest was the occurrence in the urine of an unidentified derivative of tetrahydrofolic acid, derived from orally administered pteroylglutamic acid. The presence of this compound in the urine was demonstrated chromatographically when the patient was critically ill with his disease prior to treatment with vitamin B12. Subsequent to therapy with vitamin B12, while the administration of folic acid was continued, the abnormal metabolite of folic acid could not be found in the urine. Similarly, the administration of folic acid did not lead to the appearance of this metabolite in the urine at a time when, after more than two years without specific therapy, a hematological relapse occurred that was much less severe than that previously observed. The implications of these observations, with respect to the metabolic interrelationships of folic acid and vitamin B12, are discussed. Of further interest were the findings of strongly acid gastric juice containing much mucus and free hydrochloric acid. A fairly normal gastric mucosa was demonstrated by biopsy. The meaning of these unusual findings is discussed and an hypothesis to account for them is offered. The probable sequence of events in these patients from childhood to the development of anemia, usually in later life, is set forth.

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