Interrelations of Vitamin B12 and Folic Acid Metabolism: Folic Acid Clearance Studies*

Herbert, Victor; Zalusky, Ralph

doi:10.1172/jci104589

Cited by 492 publications

(187 citation statements)

References 35 publications

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“…A few of the important pathways are visualized here. OCM is also important for providing cofactors and substrates for a multitude of subsequent reactions ranging from epigenetic methylation of genes to purine production folate, and riboflavin (Garrod et al 2010;Herbert and Zalusky 1962;Silla et al 2011;Yamada et al 2001;Yang et al 2008). MTR (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Concept mapping One-Carbon Metabolism to model future ontologies for nutrient–gene–phenotype interactions

et al. 2014

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Advances in the development of bioinformatic tools continue to improve investigators' ability to interrogate, organize, and derive knowledge from large amounts of heterogeneous information. These tools often require advanced technical skills not possessed by life scientists. User-friendly, low-barrier-to-entry methods of visualizing nutrigenomics information are yet to be developed. We utilized concept mapping software from the Institute for Human and Machine Cognition to create a conceptual model of diet and health-related data that provides a foundation for future nutrigenomics ontologies describing published nutrient-gene/polymorphism-phenotype data. In this model, maps containing phenotype, nutrient, gene product, and genetic polymorphism interactions are visualized as triples of two concepts linked together by a linking phrase. These triples, or ''knowledge propositions,'' contextualize aggregated data and information into easy-to-read knowledge maps. Maps of these triples enable visualization of genes spanning the One-Carbon Metabolism (OCM) pathway, their sequence variants, and multiple literature-mined associations including concepts relevant to nutrition, phenotypes, and health. The concept map development process documents the incongruity of information derived from pathway databases versus literature resources. This conceptual model highlights the importance of incorporating information about genes in upstream pathways that provide substrates, as well as downstream pathways that utilize products of the pathway under investigation, in this case OCM. Other genes and their polymorphisms, such as TCN2 and FUT2, although not directly involved in OCM, potentially alter OCM pathway functionality. These upstream gene products regulate substrates such as B12. Constellations of polymorphisms affecting the functionality of genes along OCM, together with substrate and cofactor availability, may impact resultant phenotypes. These conceptual maps provide a foundational framework for development of nutrient-gene/polymorphism-phenotype ontologies and systems visualization.

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Section: Discussionmentioning

confidence: 99%

“…MTR is also responsible for the catabolism of 5-methyltetrahydrofolate to tetrahydrofolate. Low MTR activity leads to a buildup of folate in the 5-methyltetrahydrofolate form, termed the ''methyl folate trap'' (Herbert and Zalusky 1962). MTRR, depicted in Fig.…”

Section: Utilizes Gene Products Frommentioning

confidence: 99%

Concept mapping One-Carbon Metabolism to model future ontologies for nutrient–gene–phenotype interactions

et al. 2014

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“…Only MG forms crossed the enterocyte's barrier as confirmed by several works in animals 30,31 , in humans 14,29,32,33 and in vitro 15,34 . The folate conjugase responsible for this hydrolysis, also called pteroyl polyglutamates hydrolase or polyglutamate hydrolase, has been detected in many tissues and medias: intestine 35,36 , blood, bile, pancreas, kidney [37][38] , brain 31 and liver 30 . Within the enterocytes, the Tetrahydrofolic Acid (THF) is produced from dihydrofolic acid by folate reductases and then converted into 5 methyl tetrahydrofolates which is the only form joining the portal circulation 19,31,39 ( Figure 2).…”

Section: Mechanismmentioning

confidence: 99%

Folates: Key Nutrients to Remember

Freha

Mihoub

Henchiri

2017

AJPRHC

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Folic acid or vitamin B9 or pteroylglutamic acid, is a relatively simple molecule with two characteristics; firstly, it must be reduced by 2 or 4 hydrogen atoms to be metabolically active which makes it sensitive to oxidation and must be protected by ascorbic acid, secondly it may include in addition to the constituent residues of the molecule, 1-7 glutamate residue at one of its ends. These polyglutamate forms that make up the largest share of food folate, must be deconjugated by a specific enzyme present in the intestinal lumen before being absorbed in the jejunum. It is in the methylated form after passing through the enterocyte it is transported in the blood, excreted in bile and reabsorbed. It must be demethylated to integrate folic cell cycle and methyl transfer, that allows the synthesis of methionine (only possible in the presence of vitamin B12), purine, serine and especially thymidylic acid, constitutive DNA. As a methyl donor that plays a fundamental role in cerebral and nervous metabolism. Folates are involved in cell division thus; any folic acid deficiency causes a slowdown in rapid multiplication systems which may lead to red blood cell disorders (macrocytic anemia), immunity, and neural tube defects, in addition to physiological disorders (cardiovascular, cancer ...). Folic acid supplementation appears to allow the correction of these disorders.

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“…Also by 1962, Herbert and Zalusky, at the Thorndike, first proposed the 'folate trap hypothesis', defining the interrelationships of vitamn B 12 and folic acid. They showed that folic acid activity 'piles up' in human serum in the presence of B 12 deficiency and that this accumulation of N5 methyl-tetrahydrofolic acid provides direct evidence of deranged folic acid metabolism due to vitamin B 12 deficiency (Herbert & Zalusky, 1962). Rosenberg et al (1969) demonstrated that intestinal mucosal enzymes participate in absorption of folate from peptide conjugates that predominate in dietary folate.…”

Section: Iron and Iron Deficiency Anaemiamentioning

confidence: 99%

Boston city hospital and the thorndike memorial laboratory: the birth of modern haematology

Elrod

Karnad

2003

Br J Haematol

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SUMMARYEstablished in 1923, the Thorndike Memorial Laboratory at Boston City Hospital was the first clinical research laboratory in a municipal hospital in the United States of America. Minot and Castle, who were the second and third directors of the Laboratory, were pioneer haematologists and clinical investigators of the highest calibre who created an atmosphere at the Laboratory that would foster patient-centred research and attract the best physician-scientists to work and train there. The haematology research division of the Laboratory made important original contributions to the understanding of the pathophysiology of anaemia, the mechanisms of red cell and platelet destruction and the phagocytic role of the spleen, the nature of haemoglobin (normal and sickle cell), the nature of haemophilia and its therapy and the early classification of lymphoma. It contributed to the Thorndike Memorial Laboratory's worldwide reputation as a model research laboratory and established its reputation as the birthplace of modern haematology.It is not merely a question of permitting universities to carry on research within the hospital walls, but of actually providing laboratories, equipment, technicians, and salaries for professional workers -it is, in fact, a question of realizing that the fostering of medical research is one of the most important means of enabling a hospital to perform its full function of giving the best medical care to the sick. Francis Weld Peabody (1923)

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Interrelations of Vitamin B12 and Folic Acid Metabolism: Folic Acid Clearance Studies*

Cited by 492 publications

References 35 publications

Concept mapping One-Carbon Metabolism to model future ontologies for nutrient–gene–phenotype interactions

Concept mapping One-Carbon Metabolism to model future ontologies for nutrient–gene–phenotype interactions

Folates: Key Nutrients to Remember

Boston city hospital and the thorndike memorial laboratory: the birth of modern haematology

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