Biochemical functions of folic acid in our body Dr Shumaila Asim 17-3-17

Folic Acid = Synthetic Form What is Folic Acid? Folate = Natural Form Folic Acid = Synthetic Form Man-Made

What is Folic Acid? Folate is the natural (complex) form found in foods such as dark-green leafy vegetables, broccoli, asparagus, lentils, beans, peanuts, strawberries, kiwi, orange juice, liver. Folate in foods can be lost through processing and cooking, reducing the amount of available folate.

Folic Acid (Pteroyl-monoglutamic acid) Pteridine       p-Aminobenzoic acid L-Glutamic acid

STRUTURE Folic acid is a conjugated molecule consisting of a pteridine ring structure linked to para-aminobenzoic acid (PABA) that forms pteroic acid. Folic acid itself is then generated through the conjugation of glutamic acid residues to pteroic acid

What Is Folic Acid? Folic acid is the synthetic form of a water soluble B vitamin that is needed to: Make new cells/cell division Make normal-shaped red blood cells Help prevent anemia Help prevent birth defects Help prevent heart disease, stroke and certain cancers.

Absorption and Metabolism Plants Folic Acid contains 7 or 5 Glutamyl Residues linked together by a peptide bond. The peptide bond is hydrolyzed by intestinal enzymes and the compound with one glutamyl residues is formed Folic acid in the form of its monoglutamyl form is absorbed only. Then it is reduced to tetrahydrofolate in the intestinal mucosa during absorption. Vitamin C is required for this reduction

All forms of folacin are equally utilized in the body More folacin is excreted in urine and feces than is accounted for in the diet, which indicates that this vitamin is also synthesized by intestinal flora Most of folacin is stored in liver Folic acid is converted to its biologically active form folinic acid in the liver

How Do We Get Folic Acid?

Foods Naturally High in Folic Acid Liver Nuts and peanut butter Dried peas or beans Juices: orange, pineapple, tomato Fruits: orange, avocado, cantaloupe Leafy green vegetables

Fortified Grain Products SOME of the cereals with 100% of the recommended daily value of folic acid per serving: Just right with crunchy nuggets Multi-grain cheerios plus Product 19 Special K Whole grain total Total corn flakes Total raisin bran

What is the Recommended Daily Value? Adults (14-years and older) 400 mcg/day Pregnancy (all ages) 600 mcg/day Breastfeeding (all ages) 500 mcg/day Previously affected pregnancy 4000 mcg/day

What are the metabolic roles of folic acid?

Metabolic Role The roles of folic acid 1) nucleic acid metabolism 2) amino acid metabolism Its role in nucleic acid metabolism involves two pathways…

Metabolic Role The first pathway involves purine and pyrimidine synthesis which makes folic acid essential for cell division and DNA and RNA synthesis. The second pathway includes synthesis of the methyl donor S-adenosylmethionine (SAM), used in hundreds of methylation reactions, including methylation of DNA (which plays a key role in gene expression).

Metabolic Role Amino acid metabolism Folic acid derivatives are needed for the conversion of the amino acid homocysteine to methionine.

Metabolic Roles Folic acid appears to reduce the risk of stroke Low blood levels of folic acid are associated with increased risk of cancer. (Breast, pancreas and colon) Damage to DNA caused by folate deficiency may be the reason.

Cardiovascular Disease Homocysteine is an amino acid in the blood, too much of it is related to a higher risk of coronary heart disease, stroke and peripheral vascular disease. Evidence suggests that homocysteine may promote atherosclerosis by damaging the inner lining of arteries and promoting blood clots. Folic acid and other B vitamins help break down homocysteine in the body.

Cancer Since folic acid is involved in the synthesis, repair and functioning of DNA (our genetic map), a deficiency may result in damage to DNA that leads to cancer. A relationship between folic acid and several types of cancers has been observed in several population-based studies but is most clearly defined for colorectal cancer and colorectal adenomas.

Alzheimer’s Disease Recent research suggests that folate deficiency and a high homocysteine level may increase the risk for development of Alzheimer's disease and vascular dementia. More clinical trials are needed.

INCREASED REQUIREMENT The predominant condition requiring an increase in the daily intake of folate is, pregnancy. pregnancy and infancy are both characterized by increased number of rapidly proliferating cells present in the blood. The need for folate will nearly double by the third trimester of pregnancy.

Prevention of Neural Tube Defect leading to spina bifida at the very early stage of pregnancy

How Do NTDs Occur? Baby’s brain and spine fail to close completely Neural tube closing properly to form spinal column and brain.

What Is a Neural Tube Defect? Spina Bifida – 60% Anencephaly – 30% Encephalocele – 10% Neural tube defects (NTDs) are the second most common cause of infant mortality. NTDs occur in 1 out of every 2,000 babies.

Deficiency Diseases Folate deficiency results in complications nearly identical to those of vitamin B12 deficiency. The most pronounced effect of folate deficiency on cellular processes is upon DNA synthesis. The result is megaloblastic anemia as for vitamin B12 deficiency.

Megaloblastic anemia

Deficiency Diseases The inability to synthesize DNA during erythrocyte maturation leads to abnormally large erythrocytes termed macrocytic anemia. Folate deficiencies are rare due to the adequate presence of folate in food. Poor dietary habits as those of chronic alcoholics can lead to folate deficiency.

Deficiency Diseases The predominant causes of folate deficiency in non- alcoholics are impaired absorption or metabolism or an increased demand for the vitamin. Certain drugs such as anticonvulsants and oral contraceptives can impair the absorption of folate. Anticonvulsants also increase the rate of folate metabolism.

Folic Acid Status May be affected by: Genetics Interactions with medications Inadequate intake or absorption

Genetic Variation The MTHFR enzyme is important for hemical reactions involving folate. A common polymorphism is found in the gene for the enzyme MTHFR (methylene tetrahydrofolate reductase), known as C677T MTHFR. Approximately 10% of the US population possess the homozygous polymorphism. Without the enzyme, homocysteine cannot be converted to methionine. As a result, homocysteine builds up in the bloodstream and methionine is depleted.

Inadequate Intake or Absorption Malabsorption syndromes, including Crohn’s disease, tropical sprue, and gluten sensitive enteropathy can result in deficiency secondary to inadequate absorption. Alcoholism leads to impaired absorption and poor diet.

Possible Toxic Effect Risk from Folic acid Toxicity is very low. Tolerable upper intake level for adult is 1 mg/day. Upper intake level is 800 ug/day for pregnant and lactating women if less than 18 years of age. Supplemental level should not increase than the upper level to prevent folic acid from masking symptoms of Vitamin B-12