Difference between revisions of "Folic Acid"

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#REDIRECT [[Folic_acid]]
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=== Define a vitamin ===
 +
*'''EXAM'''
 +
*An ''organic'' micronutrient which is required in the diet on an ongoing basis
 +
*Some can be synthesized in the body, but not always in the amounts required
 +
*'''Definitions: [http://dictionary.reference.com/search?q=vitamin dictionary.com], [http://cancerweb.ncl.ac.uk/cgi-bin/omd?query=vitamin Cancerweb OMD], [http://harrisons.accessmedicine.com/server-java/Arknoid/amed/harrisons/co_chapters/ch075/ch075_p01.html Harrison's]'''
  
 +
=== What is vitamin B? ===
 +
*Micronutrients (intake of <100mg/day)
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*Not stored appreciably (except [[Cobalamin |B<sub>12</sub>]])
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*Act biochemically in compounds called [[Coenzyme | coenzyme]]s
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*There are 8 "vitamin B"s
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*#[http://harrisons.accessmedicine.com/server-java/Arknoid/amed/harrisons/co_chapters/ch075/ch075_p01.html Thiamine (B<sub>1</sub>)]
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*#[http://harrisons.accessmedicine.com/server-java/Arknoid/amed/harrisons/co_chapters/ch075/ch075_p04.html Riboflavin (B<sub>2</sub>)]
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*#[http://harrisons.accessmedicine.com/server-java/Arknoid/amed/harrisons/co_chapters/ch075/ch075_p05.html Niacin (B<sub>3</sub>)]
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*#[http://harrisons.accessmedicine.com/server-java/Arknoid/amed/harrisons/co_chapters/ch075/ch075_p09.html Pantothenate (B<sub>5</sub>)]
 +
*#[[Pyridoxin | Pyridoxin (B<sub>6</sub>]]) ([http://harrisons.accessmedicine.com/server-java/Arknoid/amed/harrisons/co_chapters/ch075/ch075_p06.html Harrison's])
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*#[[Cobalamin | Cobalamin (B<sub>12</sub>)]]
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*#[[Folic acid |Folate (''aka'' Folic acid)]]
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*#[http://harrisons.accessmedicine.com/server-java/Arknoid/amed/harrisons/co_chapters/ch075/ch075_p08.html Biotin]
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 +
=== Define coenzyme ===
 +
See [[Coenzyme]]
 +
 +
=== Identify folate as a vitamin essential to several important biochemical reactions in 'one-carbon' metabolism ===
 +
*[http://chemfinder.cambridgesoft.com/result.asp?molid=59-30-3 Structure]
 +
*where 1C fragments are added to, or removed from, molecules
 +
*THF (Tetrahydrofolic acid), the coenzyme form of folate, is a cofactor in several important reactions
 +
*''e.g.'', glycine --> serine, thymine synthesis, purine synthesis, and methionine synthesis
 +
 +
*There are three possible consequences of poor folate nutrition
 +
**Impaired or less-than-optimal DNA synthesis
 +
**Poor ability to carry out methylation reactions
 +
**Toxic effects of increased homocysteine levels
 +
 +
=== Identify tetrahydrofolate as the coenzyme of the vitamin folacin and that tetrahydrofolate can exist in several metabolically-active forms which are specific for certain biochemical reactions ===
 +
 +
[[Image:Folatepathway.png|thumb|200px|Folate pathway in DNA synthesis]]
 +
 +
==== Methyl THF ====
 +
*Most abundant form of TFA (trifatty acids?)
 +
*Required for the conversion of homocysteine to methionine
 +
*Also requires [[Cobalamin | B<sub>12</sub>]], and is therefore the link between folate and [[Cobalamin | B<sub>12</sub>]] metabolism
 +
 +
==== Methenyl and Formyl TFA ====
 +
*Employed in Purine synthesis
 +
 +
==== Methylene TFA ====
 +
*Required for the conversion of deoxyuridylate to thymidylate, a rate-limiting reaction in DNA synthesis.
 +
 +
=== Understand that the megaloblasts present in the circulation of people with folate deficiency arise because of defects in DNA synthesis due to defects in purine and thymidine synthesis ===
 +
 +
 +
=== Identify methyltetrahydrofolate as the most abundant form of folate and the circulating form in body fluids and formed by an irreversible reaction ===
 +
 +
 +
=== Recognize that folacin deficiency can occur through dietary insufficiency, impaired absorption, defective utilization and through competitive interactions with several kinds of drugs ===
 +
*The drugs are: dilantin (anti-convulsant), barbiturates (sedatives), quinine derivatives (antimalarial), methotrexate and aminopterin (chemotherapeutic), and sulfasalazine (anti-inflammatory)
 +
 +
*Sulfa drugs are especially significant here
 +
*They do not allow bugs to make folate
 +
**this does not bother humans, since they consume folate whole, whereas microorganisms have to create folate from little bits
 +
 +
=== Recognize pregnant women and alcoholics as two populations at risk of developing folate deficiency ===
 +
 +
==== Pregnant women ====
 +
*An additional 200&mu;g is recommended for women of childbearing age on top of the dietary requirement (120-330&mu;g/day)
 +
*All women of childbearing age should consume at least 400&mu;g/day
 +
*folate supplements are associated with a reduced risk of birth defects and with lowering homocysteine levels
 +
*Lots of empirical evidence of the link between vitamin deficiency -- especially folate -- and [[Neural Tube Defects]] (pubmed criteria: "folic acid"[MeSH Terms] AND "neural tube defects"[MeSH Terms])
 +
*Compromised folate status also increases the risks of '''cleft palate/lip, congenital malformations''', and '''miscarriage'''.
 +
 +
==== Alcoholics ====
 +
*Alcoholics usually have a poorer diet
 +
*Alcohol also impairs the absorption of folate
 +
*40% of hospitalized alcoholics are folate deficient
 +
 +
=== Recognize that a prophylactic use of folate supplementation in preventing defects, and in reducing cancer and coronary heart disease, is supported by epidemiological evidence ===
 +
*'''For the pregos''': Periconceptual supplementation reduced the risk of [[Neural Tube Defects | NTDs]] in high-risk women and in women who had no history of [[Neural Tube Defects | NTD]].
 +
*'''For the cancerites''': Inadequate folate intake is associated with increased risk of '''cell dysplasia''' and of developing certain cancers
 +
**Interventions showed lower risk of dysplasia in the colon, cervix, lung and esophagus
 +
**Plays an important role in the prevention of chromosome breaks, which are crucial to oncogenic development
 +
*'''For the KFCers''': There may be a connection between folate and cardiovascular disease, mediated by homocysteine levels.
 +
**Excessive homocysteine may cause desquamation of endothelial cells, lipoprotein oxidation, or increase the adhesion of monocytes to the vessel wall
 +
**metabolism of homocysteine is affected by several enzymes which use vitamins [[Pyridoxin |B<sub>6</sub>]] and [[Cobalamin |B<sub>12</sub>]]
 +
**The link is not direct, but there are studies linking '''folate intake''' to '''reduced plasma homocysteine''' and studies linking '''increased plasma homocysteine''' to '''increased cardiovascular risk'''.
 +
 +
=== Resources ===
 +
*[http://harrisons.accessmedicine.com/server-java/Arknoid/amed/harrisons/co_chapters/ch075/ch075_p01.html Harrison's on Vitamins]
 +
*[[Media:Q3BiochemistryNotesDrFlanagan.pdf | Quarter 3 Biochemistry Lecture notes (PDF)]]

Latest revision as of 07:42, 4 November 2011

Define a vitamin

  • EXAM
  • An organic micronutrient which is required in the diet on an ongoing basis
  • Some can be synthesized in the body, but not always in the amounts required
  • Definitions: dictionary.com, Cancerweb OMD, Harrison's

What is vitamin B?

Define coenzyme

See Coenzyme

Identify folate as a vitamin essential to several important biochemical reactions in 'one-carbon' metabolism

  • Structure
  • where 1C fragments are added to, or removed from, molecules
  • THF (Tetrahydrofolic acid), the coenzyme form of folate, is a cofactor in several important reactions
  • e.g., glycine --> serine, thymine synthesis, purine synthesis, and methionine synthesis
  • There are three possible consequences of poor folate nutrition
    • Impaired or less-than-optimal DNA synthesis
    • Poor ability to carry out methylation reactions
    • Toxic effects of increased homocysteine levels

Identify tetrahydrofolate as the coenzyme of the vitamin folacin and that tetrahydrofolate can exist in several metabolically-active forms which are specific for certain biochemical reactions

Folate pathway in DNA synthesis

Methyl THF

  • Most abundant form of TFA (trifatty acids?)
  • Required for the conversion of homocysteine to methionine
  • Also requires B12, and is therefore the link between folate and B12 metabolism

Methenyl and Formyl TFA

  • Employed in Purine synthesis

Methylene TFA

  • Required for the conversion of deoxyuridylate to thymidylate, a rate-limiting reaction in DNA synthesis.

Understand that the megaloblasts present in the circulation of people with folate deficiency arise because of defects in DNA synthesis due to defects in purine and thymidine synthesis

Identify methyltetrahydrofolate as the most abundant form of folate and the circulating form in body fluids and formed by an irreversible reaction

Recognize that folacin deficiency can occur through dietary insufficiency, impaired absorption, defective utilization and through competitive interactions with several kinds of drugs

  • The drugs are: dilantin (anti-convulsant), barbiturates (sedatives), quinine derivatives (antimalarial), methotrexate and aminopterin (chemotherapeutic), and sulfasalazine (anti-inflammatory)
  • Sulfa drugs are especially significant here
  • They do not allow bugs to make folate
    • this does not bother humans, since they consume folate whole, whereas microorganisms have to create folate from little bits

Recognize pregnant women and alcoholics as two populations at risk of developing folate deficiency

Pregnant women

  • An additional 200μg is recommended for women of childbearing age on top of the dietary requirement (120-330μg/day)
  • All women of childbearing age should consume at least 400μg/day
  • folate supplements are associated with a reduced risk of birth defects and with lowering homocysteine levels
  • Lots of empirical evidence of the link between vitamin deficiency -- especially folate -- and Neural Tube Defects (pubmed criteria: "folic acid"[MeSH Terms] AND "neural tube defects"[MeSH Terms])
  • Compromised folate status also increases the risks of cleft palate/lip, congenital malformations, and miscarriage.

Alcoholics

  • Alcoholics usually have a poorer diet
  • Alcohol also impairs the absorption of folate
  • 40% of hospitalized alcoholics are folate deficient

Recognize that a prophylactic use of folate supplementation in preventing defects, and in reducing cancer and coronary heart disease, is supported by epidemiological evidence

  • For the pregos: Periconceptual supplementation reduced the risk of NTDs in high-risk women and in women who had no history of NTD.
  • For the cancerites: Inadequate folate intake is associated with increased risk of cell dysplasia and of developing certain cancers
    • Interventions showed lower risk of dysplasia in the colon, cervix, lung and esophagus
    • Plays an important role in the prevention of chromosome breaks, which are crucial to oncogenic development
  • For the KFCers: There may be a connection between folate and cardiovascular disease, mediated by homocysteine levels.
    • Excessive homocysteine may cause desquamation of endothelial cells, lipoprotein oxidation, or increase the adhesion of monocytes to the vessel wall
    • metabolism of homocysteine is affected by several enzymes which use vitamins B6 and B12
    • The link is not direct, but there are studies linking folate intake to reduced plasma homocysteine and studies linking increased plasma homocysteine to increased cardiovascular risk.

Resources