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Studies in the Metabolism of Vitamin B12

Studies in the Metabolism of Vitamin B12

Alfred Doscherholmen
Copyright Date: 1965
Edition: NED - New edition
Pages: 280
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  • Book Info
    Studies in the Metabolism of Vitamin B12
    Book Description:

    Studies in the Metabolism of Vitamin B12 was first published in 1965. Dr. Doscherholmen has conducted extensive studies of the physiological aspects of vitamin B12 metabolism in man, and in this book he describes the investigations, reports the findings, and reviews the literature. He also reports on laboratory animal studies which contribute to a knowledge of the subject. The major investigations were performed in a clinical setting and involved the administration of doses of radiocyanocobalamin, the radioactive form of vitamin B12, to patients offlicted with various diseases and to normal subjects. In order to diagnose malabsorption of B12, the Schilling test was performed on patients having pernicious anemia, partial or total gastrectomy, histamine-fasct achlorhydria, posterolateral column disease without anemia, intestinal megaloblastic anemia, regional ileitis, sprue, secondary steatorrhea, cirrhosis of the liver, leukemia, and various types of neuritis. The author assesses the most commonly used methods of testing B12 absorption, the urinary excretion test, and reports his attempts to improve the urinary recovery of radioactivity. He describes a new technique for the measurement of B12 absorption -- the plasma absorption test -- and evaluates its clinical usefulness. He also reports on studies of the basic mechanism of the Schilling test, the organ distribution of radioactivity, and the kinetics of cyanocobalamin in man after the oral ingestion of physiologic doses of radiocyanocobalamin. Additional studies described are concerned with the B12 binding power of serum as determined through an ultrafiltration technique, the enzymatic release of B12 in the small intestine of rats, and the hepatic storage of radiocyanocobalamin. There is an extensive bibliography.

    eISBN: 978-0-8166-6216-6
    Subjects: Health Sciences

Table of Contents

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  1. Front Matter
    (pp. i-vi)
  2. Table of Contents
    (pp. vii-viii)
  3. Introduction and Methods Used in This Study

      (pp. 3-14)

      In 1948 a group of investigators led by Rickes in the laboratories of Merck and Company announced that they had isolated from liver a crystalline compound which in microgram quantities had produced hematologic remissions in patients with Addison’s pernicious anemia (535). About the same time and independently of the above group, E. Lester Smith of the Glaxo Laboratories reported on the purification of the antipernicious anemia principle in the liver (589, 591) . The discovery of this new substance, vitamin B12or cyanocobalamin, was regarded as a great accomplishment because biochemists had tried in vain for years to isolate the...

  4. The Gastrointestinal Absorption of Vitamin B12 in Man

      (pp. 17-44)

      The study of the gastrointestinal absorption of vitamin B12was seriously hampered by lack of a suitable technique until radioeyanocobalamin became available for this purpose. Bioassay techniques were tried, but it was found impossible to distinguish patients with pernicious anemia from normal subjects by following the changes in serum and urinary vitamin B12in the first 24 hours after oral doses of the vitamin (122, 632). It is apparent that bioassay techniques were too insensitive to permit the use of oral test doses in the physiologic range. Measurement of the fecal excretion of vitamin B12activity by bioassay also failed...

      (pp. 45-98)

      Shortly after the urinary excretion test had been described, it was decided to investigate the value of this test in order to learn whether one could satisfactorily separate control subjects from patients with pernicious anemia by this simple method. The test was performed on two groups of patients, the first group consisting of patients with various illnesses, none of which was known to be associated with abnormalities in the absorption or metabolism of vitamin B12.The second group was expected to show abnormally low absorption of cyanocobalamin because it consisted of patients diagnosed as having pernicious anemia on clinical grounds—...

      (pp. 99-152)

      It has been said that radioactivity was not present in measurable quantities in the plasma after the ingestion of labeled cyanocobalamin (557). In order for the orally administered radioactivity to appear in the urine in the Schilling test it has, however, to pass through the blood stream. It was therefore reasoned that if a sensitive method was used it should be possible to detect the activity in the blood or plasma. This reasoning soon proved to be correct. Three factors more than anything else were responsible for the successful measurement of the radioactivity in the plasma: (a) the use of...

      (pp. 153-192)

      Despite the widespread use of the urinary excretion test over a period of years, there is a virtual absence of detailed or factual information as to the basic mechanism of this test. For example, nobody knows the exact mode of action of the parenterally injected vitamin B12.Schilling hypothesized that either the radioactivity was in a molecule which was in competition with the non-radioactive vitamin B12for the renal reabsorption mechanism, or that the non-labeled cyanocobalamin saturated the binding capacity for vitamin B12in the plasma so that the labeled cyanocobalamin absorbed from the gut would not be protein-bound, leading...

  5. Miscellaneous Studies

      (pp. 195-209)

      Vitamin B12in nature is bound to animal proteins, though proteolytic enzymes can liberate it (522). Cyanocobalamin thus released during the digestive process presumably is bound to the intrinsic factor before being absorbed by the small intestine. Recent investigations have shown that intrinsic factor can remove vitamin B12from proteins in vitro even after the inactivation of the pepsin in gastric juice (126), suggesting that the digestion of protein, in its strictest sense, is not required for the action of intrinsic factor and the absorption of vitamin B12.

      When cyanocobalamin is being absorbed from the gastrointestinal tract, it must first...

      (pp. 210-218)

      Vitamin B12is present in the serum in a free and in a bound form, as first pointed out by Ross (547). The amount of free cyanocobalamin in the serum is just a small fraction of the total serum vitamin B12(22, 421, 441). A specific B12-binding protein exists in the blood (394, 414, 418, 419, 498, 647). Some evidence indicates non-specific binding of cyanocobalamin to serum proteins as well (36, 38, 404, 546A). Furthermore, when added to it in vitro, serum also has the ability to bind additional vitamin B12(22, 26, 38, 363, 419, 443A, 498).

      Several methods...

      (pp. 219-222)

      The liver is the most important storage organ for vitamin B12.After oral or parenteral administration of radio-labeled cyanocobalamin, surface counting over various sites has shown that the liver accumulates most of the radioactivity (220, 221, 403). It also retains the radioactivity with great avidity. Indeed, from 86 to 94 per cent of the maximal activity was found after three months (221) and about 50 per cent after a year (216, 563). The biological half-life of vitamin B12in the body has recently been calculated to be approximately a year (242, 521). The liver radioactivity seems unaffected by a single...

    • 8 SUMMARY
      (pp. 223-230)

      Because of the great importance of vitamin B12studies in the investigation of patients with pernicious anemia an evaluation was made of the value of the most commonly used B12-absorption test, the urinary excretion method. In general, there was a good separation between subjects with pernicious anemia and control patients. Thus, in 29 tests performed on 21 patients with a clinical diagnosis of Addison’s pernicious anemia, a very low urinary excretion value was observed. In 80 tests on 69 control patients, 2 revealed urinary excretion values in the range found in pernicious anemia; 1 of these showed normal, the other...

    (pp. 233-262)
  7. INDEX
    (pp. 263-271)