SlideShare uma empresa Scribd logo
1 de 38
Folic acid- Chemistry, functions
and clinical significance
Namrata Chhabra
MHPE, MD, CMCL FAIMER FELLOW- REGIONAL INSTITUTION,
Principal-in-charge, Professor& Head, Department of Biochemistry,
SSR Medical College, Mauritius
Learning Objectives
• Structure of Folic acid
• Sources,
• Recommended Daily allowance,
• Absorption, transportation, storage and excretion,
• Functions and coenzyme role,
• Biological and clinical significance of folic acid
10-Jul-21 Our Biochemistry 2
Folic acid
• Folate and folic acid are forms of a water-soluble B vitamin.
• Folate occurs naturally in food, and folic acid is the synthetic form of this
vitamin.
• Synonyms:
• Liver lactobacillus Caseifactor,
• Vitamin M,
• Streptococcus lactis R (SLR) factor,
• Vitamin Bc,
• Fermentation residue factor, and
• Pteroyl glutamic acid (PGA)
10-Jul-21 Our Biochemistry 3
Structure of Folic acid
• A composite molecule
• Made up of three parts:
• A pteridine ring system (6-
methylpterin),
• Para-amino benzoic acid, and
• Glutamic acid.
10-Jul-21 Our Biochemistry 4
Chemical forms of folic acid
• Monoglutamate (Vitamin Bc): Having one glutamic acid.
• Triglutamate“fermentation factor”: Having three glutamic acid
residues.
• Heptaglutamate (vitamin Bc conjugate of yeast ): Having seven
glutamate residues.
10-Jul-21 Our Biochemistry 5
Role of structural components of folic acid
• The glutamic acid doesn't participate in the coenzyme functions of
folic acid.
• Folic acid in the interior of the cell may contain a “chain” of three to
eight glutamic acid residues, which serves as a negatively charged
“handle” to keep the coenzyme inside cells and/or bound to the
appropriate enzymes.
• The pteridine portion of the coenzyme and the p-amino benzoic acid
portion participate directly in the metabolic reactions of folate.
10-Jul-21 Our Biochemistry 6
Sources of folic acid
• Green leafy vegetables (such
as spinach, broccoli, and
lettuce), okra, asparagus,
• Fruits (such as bananas,
melons, and lemons)beans,
yeast, mushrooms,
• Meat (such as beef liver and
kidney),
• Orange juice, and tomato
juice.
• Many microorganisms
including those inhabiting the
intestinal tract can synthesize
folic acid.
10-Jul-21 Our Biochemistry 7
Recommended daily allowance (RDA)
• Since 1998, as required by federal law, folic acid has been added to
cold cereals, flour, breads, pasta, bakery items, cookies, and crackers.
• Daily requirements of 50–100 mcg/d are usually met in the diet.
• Total body stores of folate are approximately 5000 mcg, enough to
supply requirements for 2–3 months.
10-Jul-21 Our Biochemistry 8
Absorption of folic acid
• Absorption occurs along the whole length of mucosa of small
intestine.
• Polyglutamates ingested in diet are converted to mono-glutamates
• Dihydrofolates are reduced to tetrahydrofolates by folate reductase
• Tetrahydrofolates are then converted to methyl tetrahydrofolates,
which enter the portal blood and then carried to liver.
• Conjugases (γ-glutamyl carboxypeptidases) in the intestinal lumen
cleave off extra glutamic acid residues before absorption of folate in
the small intestine.
10-Jul-21 Our Biochemistry 9
Transportation, plasma and tissue levels
• Transportation-Folate is transported in blood as methyl
tetrahydrofolate bound to a specific protein.
• Plasma level: In normal individuals, it varies from 3 to 21 ng/ml.
• Tissue folate: About 70 mg in the whole body, of which about 1/3 (5
to 15 μg/g) is in the liver.
• RB cells folate: Folate is incorporated into the RB cells during
erythropoiesis and is retained there during their entire life span.
• Red cell folate is a reliable indicator of the folate status of the body.
• Average level is 300 ng/ml of whole blood (range 160–640 ng/ml).
10-Jul-21 Our Biochemistry 10
Excretion of folate
• Urine: 2 to 5 μg/day.
• Excretion is much increased after an oral dose of folate if the tissues
are saturated.
• Feces contain 20 per cent of the ingested folates that remains
unabsorbed and some unabsorbed synthesis of folate by bacterial
flora of intestine.
10-Jul-21 Our Biochemistry 11
Activation of folic acid
• Folic acid, before functioning as a
coenzyme, must be reduced first
to 7, 8-dihydrofolic acid(F.H2) and
then to 5, 6, 7, 8 tetrahydrofolate
(F.H4).
• Both the reactions are catalyzed by
Folic acid reductases enzyme,
which use NADPH as hydrogen
donor.
• This enzyme also requires vitamin
C (ascorbic acid) as a cofactor.
10-Jul-21 Our Biochemistry 12
Biologically active forms of folic acid
Active “coenzyme” form of the vitamin is the reduced tetrahydro
derivative, Tetrahydrofolate F.H4, obtained by addition
of four hydrogens to the pteridine moiety at 5, 6, 7 and 8
position.
The other forms occur only in small quantities.
10-Jul-21 Our Biochemistry 13
Functions of folic acid
• One carbon metabolism-Folates act as coenzymes in the transfer of
single-carbon units.
• Replication and Transcription- Folate is involved in purine and
pyrimidine synthesis required for DNA and RNA synthesis.
• Folate is also a coenzyme for methionine synthesis, in which
Methylcobalamine is also involved.
10-Jul-21 Our Biochemistry 14
One carbon compounds
• One carbon moiety (C1) may be either:
• Methyl (–CH3),
• Formyl (–CHO),
• Formate (H.COOH),
• Formimino group (–CH=NH) or
• Hydroxymethyl (–CH2OH).
• Most of them are metabolically “interconvertible”
10-Jul-21 Our Biochemistry 15
Sources of one carbon fragments
• One carbon fragments are produced by the metabolism of :
• Serine
• Glycine
• Tryptophan
• Histidine, and
• Choline
10-Jul-21 Our Biochemistry 16
Utilization of one carbon fragments
• Methylene-, methenyl-, and 10-formyl-
tetrahydrofolates are interconvertible.
• The methylene form donates its methyl
group during the biosynthesis of
thymidine nucleotides for DNA synthesis,
• the methenyl form donates its group as a
Formyl group during purine biosynthesis,
and
• the methyl form is the donor of the
methyl group to sulfur during methionine
formation.
• When one-carbon folates are not
required, the oxidation of formyl-
tetrahydrofolate to yield carbon dioxide
provides a means of maintaining a pool of
free folate.
10-Jul-21 Our Biochemistry 17
Role of folic acid in nucleotide synthesis
• Two different forms of folate are
required for different aspects of
nucleotide biosynthesis.
• N10-formyl THF provides the C-2 and
C-8 carbons for the de novo synthesis
of purine rings, and thus is critical for
DNA metabolism.
10-Jul-21 Our Biochemistry 18
Role of folic acid in nucleotide synthesis
• The Methylene
form, N5,N10-
methylene THF, is
required for the
production of dTMP
from dUMP.
• Methotrexate,
inhibits
dihydrofolate
reductase and has
been exploited as an
anti-cancer
10-Jul-21 Our Biochemistry 19
Role of folic acid in Trans Methylation
reactions and Folate trap
• In the absence of B12,
THF can be trapped in
the N5-methyl THF
form and thus be
removed from the THF
pool. This is referred to
as the “methyl trap,”
which can impact other
areas of 1-carbon
metabolism, such as
dTMP production.
10-Jul-21 Our Biochemistry 20
Summary of functions of folic acid
10-Jul-21 Our Biochemistry 21
Folate antagonists
• 1) Sulfanilamide is the simplest of the sulfa
drugs, used as antibacterial agents.
• Because of structural similarity to p-
aminobenzoic acid, sulfanilamide inhibits the
growth of bacteria by interfering with their
ability to use p-aminobenzoic acid to synthesize
folic acid.
• Because humans don't make folic acid,
sulfanilamide is not toxic to humans in the doses
that inhibit bacteria.
10-Jul-21 Our Biochemistry 22
Folate antagonists
2) Trimethoprim and
Pyrimethamine
• The dihydrofolate reductases
of some bacteria and
parasites differ from the
human enzyme;
• Inhibitors of these enzymes
can be used as antibacterial
drugs (e.g., trimethoprim)
and Antimalarial drugs (e.g.,
pyrimethamine).
10-Jul-21 Our Biochemistry 23
Folate antagonists used as anti cancer drugs
1) Methotrexate, an analog of 10-methyl-tetrahydrofolate, inhibits
dihydrofolate reductase and has been exploited as an anti-cancer
2) Aminopterin is also an inhibitor of DHFR enzyme and is used as an
anticancer drug.
3) Trimetrexate, Lometrexol and Pemetrexed are also some of the
upcoming folate antagonists used in cancer chemotherapy.
10-Jul-21 Our Biochemistry 24
Leucovorin (LV)
• Leucovorin (LV) is a form of folic acid that can help "rescue" or reverse
the toxic effects of methotrexate.
• LV is not a folate antagonist per se, but the folate derivative 5-
formyltetrahydrofolate.
• N5-formyl THF is normally administered 24 hours following
treatment with methotrexate;
• It can be converted to THF by these normal cells by bypassing the
block caused by methotrexate.
• Therefore, these normal cells can synthesize deoxy thymidine and
carry out DNA synthesis.
10-Jul-21 Our Biochemistry 25
Megaloblastic anemia due to folate deficiency
• Inadequate dietary intake.
• Alcoholics, anorectic patients, persons who do not eat fresh fruits and
vegetables, and those who overcook their food are candidates for folate
deficiency.
• Drugs such as phenytoin, trimethoprim-sulfamethoxazole, or Sulfasalazine
may interfere with folate absorption.
• Folic acid requirements are increased in pregnancy, hemolytic anemia, and
exfoliative skin disease, and in these cases the increased requirements (five
to ten times normal) may not be met by a normal diet.
• Patients with increased folate requirements should receive
supplementation with 1 mg/d of folic acid.
10-Jul-21 Our Biochemistry 26
Biochemical Basis of Megaloblastic Anemia
• The common feature of all megaloblastic anemias is a defect in DNA
synthesis that affects rapidly dividing cells in the bone marrow.
• In deficiencies of either folate or cobalamin, there is failure to convert
deoxy uridine monophosphate (dUMP) to deoxythymidine
monophosphate (dTMP), the precursor of dTTP.
• This is because folate is needed as the coenzyme 5, 10-methylene-
THF polyglutamate for conversion of dUMP to dTMP; the availability
of 5, 10-methylene-THF is reduced in either cobalamin or folate
deficiency.
10-Jul-21 Our Biochemistry 27
Clinical manifestations
• History:
• The patient's history is important because it may reveal the
underlying disorder.
• Very often, a patient presents with a history of excessive alcohol
intake with concurrent poor diet intake.
• Other times, patients may be pregnant or lactating;
• may take certain drugs, such as phenytoin, sulfonamides, or
methotrexate;
• may have chronic hemolytic anemia; or
• may have underlying malabsorption.
10-Jul-21 Our Biochemistry 28
Clinical manifestations
2.Oral lesions
• Some patients complain of a sore tongue or pain
upon swallowing.
• The tongue may appear swollen, beefy, red, or shiny,
usually around the edges and tips initially.
• Angular stomatitis also may be observed.
• These oral lesions typically occur at the time when
folate depletion is severe enough to cause
megaloblastic anemia, although, occasionally, lesions
may occur before the anemia
10-Jul-21 Our Biochemistry 29
Clinical manifestations
• GI symptoms
• Patients may present with GI symptoms, such as nausea, vomiting,
abdominal pain, and diarrhea, especially after meals.
• Anorexia also is common and, in combination with the above
symptoms, may lead to marked weight loss.
10-Jul-21 Our Biochemistry 30
Clinical manifestations
• 4. Hyperpigmentation
• Patients with folate deficiency may have darkening of the skin and
mucous membranes, particularly at the dorsal surfaces of the fingers,
toes, and creases of palms and soles.
• Distribution typically is patchy.
• The hyperpigmentation gradually should resolve after weeks or
months of folate treatment.
• A modest temperature elevation (<102°F) is common in patients who
are folate deficient, despite the absence of any infection.
10-Jul-21 Our Biochemistry 31
Laboratory Investigations
• Serum folate (reference range 2.5-20 ng/mL) and serum cobalamin
(reference range 200-900 pg/mL)
• Ruling out cobalamin deficiency is very important because folate treatment
will not improve neurologic abnormalities due to cobalamin deficiency.
• Additional follow-up tests include serum homocysteine (reference range 5-
16 mmol/L), which is elevated in B-12 and folate deficiency, and serum
methylmalonic acid (reference range 70-270 mmol/L), which is elevated in
B-12 deficiency only.
• Red blood cell folate levels (reference range >140 ng/mL) tend to reflect
chronic folate status rather than acute changes in folate that are reflected
in serum folate levels,
10-Jul-21 Our Biochemistry 32
Laboratory Investigations
• Hematological Findings
• Peripheral Blood film
• Oval macrocytes, usually with considerable anisocytosis and poikilocytosis,
are the main feature.
• The MCV is usually >100 fL unless a cause of microcytosis (e.g., iron
deficiency or thalassemia trait) is present.
• Some of the neutrophils are hyper segmented (more than five nuclear
lobes).
• There may be leucopenia due to a reduction in granulocytes and
lymphocytes, but this is usually >1.5 x 109/L;
• the platelet count may be moderately reduced, rarely to <40 x 109/L.
• The severity of all these changes parallels the degree of anemia.
10-Jul-21 Our Biochemistry 33
Laboratory Investigations
• Bone Marrow
• Bone marrow morphology is characteristically abnormal.
• Marked erythroid hyperplasia is present as a response to defective
red blood cell production (ineffective erythropoiesis).
• Megaloblastic changes in the erythroid series include abnormally
large cell size and asynchronous maturation of the nucleus and
cytoplasm—i.e., cytoplasmic maturation continues while impaired
DNA synthesis causes retarded nuclear development.
• In the myeloid series, giant metamyelocytes are characteristically
seen
10-Jul-21 Our Biochemistry 34
Treatment
• Oral doses of 5–15 mg folic acid daily are satisfactory.
• It is customary to continue therapy for about 4 months, when all folate-
deficient red cells will have been eliminated and replaced by new folate-
replete populations.
• Cobalamin deficiency must be excluded and, if present, corrected,
otherwise cobalamin neuropathy may develop, despite a response of the
anemia of cobalamin deficiency to folate therapy.
• Long-term folic acid therapy is required when the underlying cause of the
deficiency cannot be corrected, and the deficiency is likely to recur.
• In any patient receiving long-term folic acid therapy, it is important to
measure the serum cobalamin level at regular (e.g., once yearly) intervals
to exclude the coincidental development of cobalamin deficiency.
10-Jul-21 Our Biochemistry 35
Therapeutic significance of folate
supplementation
• Folic acid is used for preventing and treating low blood levels of folate (folate
deficiency) and high blood levels of homocysteine (Hyperhomocysteinemia).
• Women who are pregnant or might become pregnant take folic acid to prevent
miscarriage and "neural tube defects "such as spina bifida.
• Folic acid is also used for many other conditions including depression, stroke,
decline in memory and thinking skills in older people
10-Jul-21 Our Biochemistry 36
Summary
• A composite molecule, made up of three parts :a pteridine ring
system, para-amino benzoic acid, and glutamic acid.
• Daily requirement is 50–100 mcg/d.
• Total body stores of folate are approximately 5000 mcg.
• Participates in one carbon metabolism, nucleotide biosynthesis and
as a coenzyme for methionine synthesis.
• In the absence of B12, THF can be trapped in the N5-methyl THF
form.
• Folate antagonists act as antibiotics and anticancer drugs.
• Folate deficiency causes megaloblastic anemia.
10-Jul-21 Our Biochemistry 37
Thank you
10-Jul-21 Our Biochemistry 38

Mais conteúdo relacionado

Mais procurados

Mais procurados (20)

Folic acid
Folic acid Folic acid
Folic acid
 
NIACIN (B3)
NIACIN (B3)NIACIN (B3)
NIACIN (B3)
 
Vitamin b9
Vitamin b9Vitamin b9
Vitamin b9
 
BIOTIN (B7)
BIOTIN (B7)BIOTIN (B7)
BIOTIN (B7)
 
Folic acid
Folic acidFolic acid
Folic acid
 
Vitamin b9
Vitamin b9Vitamin b9
Vitamin b9
 
Cobalamine (B12)
Cobalamine (B12)Cobalamine (B12)
Cobalamine (B12)
 
Thiamine
ThiamineThiamine
Thiamine
 
Sulphur containing amino acids metabolism
Sulphur containing  amino acids metabolism Sulphur containing  amino acids metabolism
Sulphur containing amino acids metabolism
 
Vitamin b1
Vitamin b1Vitamin b1
Vitamin b1
 
Folic acid and derivatives
Folic acid and derivativesFolic acid and derivatives
Folic acid and derivatives
 
Metabolism of Phenylalanine and Tyrosine
Metabolism of Phenylalanine and TyrosineMetabolism of Phenylalanine and Tyrosine
Metabolism of Phenylalanine and Tyrosine
 
Vitamin b5, pantothenic acid
Vitamin b5, pantothenic acidVitamin b5, pantothenic acid
Vitamin b5, pantothenic acid
 
Thiamine
ThiamineThiamine
Thiamine
 
Vitamin B12- Chemistry, functions and clinical significance
Vitamin B12- Chemistry, functions and clinical significanceVitamin B12- Chemistry, functions and clinical significance
Vitamin B12- Chemistry, functions and clinical significance
 
Phenylalanine & tyrosine amino acid metabolism
Phenylalanine & tyrosine amino acid metabolismPhenylalanine & tyrosine amino acid metabolism
Phenylalanine & tyrosine amino acid metabolism
 
One carbon metabolism
One carbon metabolism One carbon metabolism
One carbon metabolism
 
Folic acid
Folic acidFolic acid
Folic acid
 
Vitamin A
Vitamin AVitamin A
Vitamin A
 
THIAMINE (B1)
THIAMINE (B1)THIAMINE (B1)
THIAMINE (B1)
 

Semelhante a Folic acid- Chemistry, One carbon metabolism and megaloblastic anemia

megaloblastic anaemia notes cology topic
megaloblastic anaemia notes cology topicmegaloblastic anaemia notes cology topic
megaloblastic anaemia notes cology topicAffrin Shaik
 
Updated Folic Acid.ppt
Updated Folic Acid.pptUpdated Folic Acid.ppt
Updated Folic Acid.pptMVerghese
 
vitamins in nutrient metabolism.pptx
vitamins in nutrient metabolism.pptxvitamins in nutrient metabolism.pptx
vitamins in nutrient metabolism.pptxDrVineethaPG
 
FOLIC ACID-vit b9.pptx
FOLIC ACID-vit b9.pptxFOLIC ACID-vit b9.pptx
FOLIC ACID-vit b9.pptxBRMHi
 
Vitamins & Minerals
Vitamins & MineralsVitamins & Minerals
Vitamins & MineralsAhmed Madni
 
chapter 5 vitamins.ppt
chapter 5 vitamins.pptchapter 5 vitamins.ppt
chapter 5 vitamins.pptFatima117039
 
7 vitamins and cofactors
7 vitamins and cofactors7 vitamins and cofactors
7 vitamins and cofactorsSiham Gritly
 
Treatment of other anemias
Treatment  of other anemiasTreatment  of other anemias
Treatment of other anemiasRudhra Prabhakar
 
Megaloblastic anaemia
Megaloblastic anaemiaMegaloblastic anaemia
Megaloblastic anaemiaRaghav Kakar
 
Lec56 level4-defatsolublevitamins-130202064226-phpapp01
Lec56 level4-defatsolublevitamins-130202064226-phpapp01Lec56 level4-defatsolublevitamins-130202064226-phpapp01
Lec56 level4-defatsolublevitamins-130202064226-phpapp01Cleophas Rwemera
 
Physiologicak roles of vitamins
Physiologicak roles of vitaminsPhysiologicak roles of vitamins
Physiologicak roles of vitaminsSiham Gritly
 
Absorption, transport and metabolism of folate
Absorption, transport and metabolism of folateAbsorption, transport and metabolism of folate
Absorption, transport and metabolism of folateDomina Petric
 
Lec 7 level 4-de (water soluble vitamins)
Lec 7 level 4-de (water soluble vitamins)Lec 7 level 4-de (water soluble vitamins)
Lec 7 level 4-de (water soluble vitamins)dream10f
 
vitamins%20edit.pptx
vitamins%20edit.pptxvitamins%20edit.pptx
vitamins%20edit.pptxatthibnys
 

Semelhante a Folic acid- Chemistry, One carbon metabolism and megaloblastic anemia (20)

229983 lecture 26
229983 lecture 26229983 lecture 26
229983 lecture 26
 
229983 lecture 26
229983 lecture 26229983 lecture 26
229983 lecture 26
 
megaloblastic anaemia notes cology topic
megaloblastic anaemia notes cology topicmegaloblastic anaemia notes cology topic
megaloblastic anaemia notes cology topic
 
Updated Folic Acid.ppt
Updated Folic Acid.pptUpdated Folic Acid.ppt
Updated Folic Acid.ppt
 
vitamins in nutrient metabolism.pptx
vitamins in nutrient metabolism.pptxvitamins in nutrient metabolism.pptx
vitamins in nutrient metabolism.pptx
 
FOLIC ACID-vit b9.pptx
FOLIC ACID-vit b9.pptxFOLIC ACID-vit b9.pptx
FOLIC ACID-vit b9.pptx
 
Vitamins & Minerals
Vitamins & MineralsVitamins & Minerals
Vitamins & Minerals
 
chapter 5 vitamins.ppt
chapter 5 vitamins.pptchapter 5 vitamins.ppt
chapter 5 vitamins.ppt
 
7 vitamins and cofactors
7 vitamins and cofactors7 vitamins and cofactors
7 vitamins and cofactors
 
Metabolism of Vitamin B12 and Folic Acid
Metabolism of Vitamin B12 and Folic Acid Metabolism of Vitamin B12 and Folic Acid
Metabolism of Vitamin B12 and Folic Acid
 
Treatment of other anemias
Treatment  of other anemiasTreatment  of other anemias
Treatment of other anemias
 
Megaloblastic anaemia
Megaloblastic anaemiaMegaloblastic anaemia
Megaloblastic anaemia
 
Lec56 level4-defatsolublevitamins-130202064226-phpapp01
Lec56 level4-defatsolublevitamins-130202064226-phpapp01Lec56 level4-defatsolublevitamins-130202064226-phpapp01
Lec56 level4-defatsolublevitamins-130202064226-phpapp01
 
Physiologicak roles of vitamins
Physiologicak roles of vitaminsPhysiologicak roles of vitamins
Physiologicak roles of vitamins
 
Calcium
CalciumCalcium
Calcium
 
Absorption, transport and metabolism of folate
Absorption, transport and metabolism of folateAbsorption, transport and metabolism of folate
Absorption, transport and metabolism of folate
 
Vitamin B9-2.pptx
Vitamin B9-2.pptxVitamin B9-2.pptx
Vitamin B9-2.pptx
 
vitamin b9 and b12.pptx
vitamin b9 and b12.pptxvitamin b9 and b12.pptx
vitamin b9 and b12.pptx
 
Lec 7 level 4-de (water soluble vitamins)
Lec 7 level 4-de (water soluble vitamins)Lec 7 level 4-de (water soluble vitamins)
Lec 7 level 4-de (water soluble vitamins)
 
vitamins%20edit.pptx
vitamins%20edit.pptxvitamins%20edit.pptx
vitamins%20edit.pptx
 

Mais de Namrata Chhabra

Applications of Recombinant DNA Technology
Applications of Recombinant DNA Technology Applications of Recombinant DNA Technology
Applications of Recombinant DNA Technology Namrata Chhabra
 
Recombinant DNA Technology- Part 1.pdf
Recombinant DNA Technology- Part 1.pdfRecombinant DNA Technology- Part 1.pdf
Recombinant DNA Technology- Part 1.pdfNamrata Chhabra
 
Polymerase Chain Reaction- Principle, procedure, and applications of PCR
Polymerase Chain Reaction- Principle, procedure, and applications of PCRPolymerase Chain Reaction- Principle, procedure, and applications of PCR
Polymerase Chain Reaction- Principle, procedure, and applications of PCRNamrata Chhabra
 
Clinical case discussions
Clinical case discussions Clinical case discussions
Clinical case discussions Namrata Chhabra
 
Basal metabolic rate (BMR)- Factors affecting BMR, measurement and clinical s...
Basal metabolic rate (BMR)- Factors affecting BMR, measurement and clinical s...Basal metabolic rate (BMR)- Factors affecting BMR, measurement and clinical s...
Basal metabolic rate (BMR)- Factors affecting BMR, measurement and clinical s...Namrata Chhabra
 
Selenium- chemistry, functions and clinical significance
Selenium- chemistry, functions and clinical significanceSelenium- chemistry, functions and clinical significance
Selenium- chemistry, functions and clinical significanceNamrata Chhabra
 
Vitamin B12-Chemistry, functions and clinical significance
Vitamin B12-Chemistry, functions and clinical significanceVitamin B12-Chemistry, functions and clinical significance
Vitamin B12-Chemistry, functions and clinical significanceNamrata Chhabra
 
Sugar derivatives and reactions of monosaccharides
Sugar derivatives and reactions of monosaccharidesSugar derivatives and reactions of monosaccharides
Sugar derivatives and reactions of monosaccharidesNamrata Chhabra
 
Chemistry of carbohydrates part 2
Chemistry of carbohydrates part 2 Chemistry of carbohydrates part 2
Chemistry of carbohydrates part 2 Namrata Chhabra
 
Chemistry of carbohydrates - General introduction and classification
Chemistry of carbohydrates - General introduction and classificationChemistry of carbohydrates - General introduction and classification
Chemistry of carbohydrates - General introduction and classificationNamrata Chhabra
 
Protein misfolding diseases
Protein misfolding diseasesProtein misfolding diseases
Protein misfolding diseasesNamrata Chhabra
 
Protein structure, Protein unfolding and misfolding
Protein structure, Protein unfolding and misfoldingProtein structure, Protein unfolding and misfolding
Protein structure, Protein unfolding and misfoldingNamrata Chhabra
 
Molecular biology revision-Part 3 (Regulation of genes expression and Recombi...
Molecular biology revision-Part 3 (Regulation of genes expression and Recombi...Molecular biology revision-Part 3 (Regulation of genes expression and Recombi...
Molecular biology revision-Part 3 (Regulation of genes expression and Recombi...Namrata Chhabra
 
Revision Molecular biology- Part 2
Revision Molecular biology- Part 2Revision Molecular biology- Part 2
Revision Molecular biology- Part 2Namrata Chhabra
 
Molecular Biology Revision-Part1
Molecular Biology Revision-Part1Molecular Biology Revision-Part1
Molecular Biology Revision-Part1Namrata Chhabra
 
A quick revision of Carbohydrate metabolism with case- based discussions and ...
A quick revision of Carbohydrate metabolism with case- based discussions and ...A quick revision of Carbohydrate metabolism with case- based discussions and ...
A quick revision of Carbohydrate metabolism with case- based discussions and ...Namrata Chhabra
 

Mais de Namrata Chhabra (20)

Applications of Recombinant DNA Technology
Applications of Recombinant DNA Technology Applications of Recombinant DNA Technology
Applications of Recombinant DNA Technology
 
Recombinant DNA Technology- Part 1.pdf
Recombinant DNA Technology- Part 1.pdfRecombinant DNA Technology- Part 1.pdf
Recombinant DNA Technology- Part 1.pdf
 
Polymerase Chain Reaction- Principle, procedure, and applications of PCR
Polymerase Chain Reaction- Principle, procedure, and applications of PCRPolymerase Chain Reaction- Principle, procedure, and applications of PCR
Polymerase Chain Reaction- Principle, procedure, and applications of PCR
 
Clinical case discussions
Clinical case discussions Clinical case discussions
Clinical case discussions
 
Basal metabolic rate (BMR)- Factors affecting BMR, measurement and clinical s...
Basal metabolic rate (BMR)- Factors affecting BMR, measurement and clinical s...Basal metabolic rate (BMR)- Factors affecting BMR, measurement and clinical s...
Basal metabolic rate (BMR)- Factors affecting BMR, measurement and clinical s...
 
Selenium- chemistry, functions and clinical significance
Selenium- chemistry, functions and clinical significanceSelenium- chemistry, functions and clinical significance
Selenium- chemistry, functions and clinical significance
 
Copper metabolism
Copper metabolismCopper metabolism
Copper metabolism
 
Biotin
BiotinBiotin
Biotin
 
Vitamin B12-Chemistry, functions and clinical significance
Vitamin B12-Chemistry, functions and clinical significanceVitamin B12-Chemistry, functions and clinical significance
Vitamin B12-Chemistry, functions and clinical significance
 
Sugar derivatives and reactions of monosaccharides
Sugar derivatives and reactions of monosaccharidesSugar derivatives and reactions of monosaccharides
Sugar derivatives and reactions of monosaccharides
 
Chemistry of carbohydrates part 2
Chemistry of carbohydrates part 2 Chemistry of carbohydrates part 2
Chemistry of carbohydrates part 2
 
Chemistry of carbohydrates - General introduction and classification
Chemistry of carbohydrates - General introduction and classificationChemistry of carbohydrates - General introduction and classification
Chemistry of carbohydrates - General introduction and classification
 
ELISA- a quick revision
ELISA- a quick revisionELISA- a quick revision
ELISA- a quick revision
 
Protein misfolding diseases
Protein misfolding diseasesProtein misfolding diseases
Protein misfolding diseases
 
Protein structure, Protein unfolding and misfolding
Protein structure, Protein unfolding and misfoldingProtein structure, Protein unfolding and misfolding
Protein structure, Protein unfolding and misfolding
 
Molecular biology revision-Part 3 (Regulation of genes expression and Recombi...
Molecular biology revision-Part 3 (Regulation of genes expression and Recombi...Molecular biology revision-Part 3 (Regulation of genes expression and Recombi...
Molecular biology revision-Part 3 (Regulation of genes expression and Recombi...
 
Revision Molecular biology- Part 2
Revision Molecular biology- Part 2Revision Molecular biology- Part 2
Revision Molecular biology- Part 2
 
Molecular Biology Revision-Part1
Molecular Biology Revision-Part1Molecular Biology Revision-Part1
Molecular Biology Revision-Part1
 
Enzymology quiz
Enzymology quizEnzymology quiz
Enzymology quiz
 
A quick revision of Carbohydrate metabolism with case- based discussions and ...
A quick revision of Carbohydrate metabolism with case- based discussions and ...A quick revision of Carbohydrate metabolism with case- based discussions and ...
A quick revision of Carbohydrate metabolism with case- based discussions and ...
 

Último

How to Send Emails From Odoo 17 Using Code
How to Send Emails From Odoo 17 Using CodeHow to Send Emails From Odoo 17 Using Code
How to Send Emails From Odoo 17 Using CodeCeline George
 
P4C x ELT = P4ELT: Its Theoretical Background (Kanazawa, 2024 March).pdf
P4C x ELT = P4ELT: Its Theoretical Background (Kanazawa, 2024 March).pdfP4C x ELT = P4ELT: Its Theoretical Background (Kanazawa, 2024 March).pdf
P4C x ELT = P4ELT: Its Theoretical Background (Kanazawa, 2024 March).pdfYu Kanazawa / Osaka University
 
CHUYÊN ĐỀ DẠY THÊM TIẾNG ANH LỚP 11 - GLOBAL SUCCESS - NĂM HỌC 2023-2024 - HK...
CHUYÊN ĐỀ DẠY THÊM TIẾNG ANH LỚP 11 - GLOBAL SUCCESS - NĂM HỌC 2023-2024 - HK...CHUYÊN ĐỀ DẠY THÊM TIẾNG ANH LỚP 11 - GLOBAL SUCCESS - NĂM HỌC 2023-2024 - HK...
CHUYÊN ĐỀ DẠY THÊM TIẾNG ANH LỚP 11 - GLOBAL SUCCESS - NĂM HỌC 2023-2024 - HK...Nguyen Thanh Tu Collection
 
CapTechU Doctoral Presentation -March 2024 slides.pptx
CapTechU Doctoral Presentation -March 2024 slides.pptxCapTechU Doctoral Presentation -March 2024 slides.pptx
CapTechU Doctoral Presentation -March 2024 slides.pptxCapitolTechU
 
How to Create a Toggle Button in Odoo 17
How to Create a Toggle Button in Odoo 17How to Create a Toggle Button in Odoo 17
How to Create a Toggle Button in Odoo 17Celine George
 
DUST OF SNOW_BY ROBERT FROST_EDITED BY_ TANMOY MISHRA
DUST OF SNOW_BY ROBERT FROST_EDITED BY_ TANMOY MISHRADUST OF SNOW_BY ROBERT FROST_EDITED BY_ TANMOY MISHRA
DUST OF SNOW_BY ROBERT FROST_EDITED BY_ TANMOY MISHRATanmoy Mishra
 
Ultra structure and life cycle of Plasmodium.pptx
Ultra structure and life cycle of Plasmodium.pptxUltra structure and life cycle of Plasmodium.pptx
Ultra structure and life cycle of Plasmodium.pptxDr. Asif Anas
 
AUDIENCE THEORY -- FANDOM -- JENKINS.pptx
AUDIENCE THEORY -- FANDOM -- JENKINS.pptxAUDIENCE THEORY -- FANDOM -- JENKINS.pptx
AUDIENCE THEORY -- FANDOM -- JENKINS.pptxiammrhaywood
 
How to Show Error_Warning Messages in Odoo 17
How to Show Error_Warning Messages in Odoo 17How to Show Error_Warning Messages in Odoo 17
How to Show Error_Warning Messages in Odoo 17Celine George
 
KARNAADA.pptx made by - saransh dwivedi ( SD ) - SHALAKYA TANTRA - ENT - 4...
KARNAADA.pptx  made by -  saransh dwivedi ( SD ) -  SHALAKYA TANTRA - ENT - 4...KARNAADA.pptx  made by -  saransh dwivedi ( SD ) -  SHALAKYA TANTRA - ENT - 4...
KARNAADA.pptx made by - saransh dwivedi ( SD ) - SHALAKYA TANTRA - ENT - 4...M56BOOKSTORE PRODUCT/SERVICE
 
Work Experience for psp3 portfolio sasha
Work Experience for psp3 portfolio sashaWork Experience for psp3 portfolio sasha
Work Experience for psp3 portfolio sashasashalaycock03
 
How to Add Existing Field in One2Many Tree View in Odoo 17
How to Add Existing Field in One2Many Tree View in Odoo 17How to Add Existing Field in One2Many Tree View in Odoo 17
How to Add Existing Field in One2Many Tree View in Odoo 17Celine George
 
The basics of sentences session 10pptx.pptx
The basics of sentences session 10pptx.pptxThe basics of sentences session 10pptx.pptx
The basics of sentences session 10pptx.pptxheathfieldcps1
 
Easter in the USA presentation by Chloe.
Easter in the USA presentation by Chloe.Easter in the USA presentation by Chloe.
Easter in the USA presentation by Chloe.EnglishCEIPdeSigeiro
 
Prescribed medication order and communication skills.pptx
Prescribed medication order and communication skills.pptxPrescribed medication order and communication skills.pptx
Prescribed medication order and communication skills.pptxraviapr7
 
Riddhi Kevadiya. WILLIAM SHAKESPEARE....
Riddhi Kevadiya. WILLIAM SHAKESPEARE....Riddhi Kevadiya. WILLIAM SHAKESPEARE....
Riddhi Kevadiya. WILLIAM SHAKESPEARE....Riddhi Kevadiya
 
Unveiling the Intricacies of Leishmania donovani: Structure, Life Cycle, Path...
Unveiling the Intricacies of Leishmania donovani: Structure, Life Cycle, Path...Unveiling the Intricacies of Leishmania donovani: Structure, Life Cycle, Path...
Unveiling the Intricacies of Leishmania donovani: Structure, Life Cycle, Path...Dr. Asif Anas
 
Vani Magazine - Quarterly Magazine of Seshadripuram Educational Trust
Vani Magazine - Quarterly Magazine of Seshadripuram Educational TrustVani Magazine - Quarterly Magazine of Seshadripuram Educational Trust
Vani Magazine - Quarterly Magazine of Seshadripuram Educational TrustSavipriya Raghavendra
 
How to Make a Field read-only in Odoo 17
How to Make a Field read-only in Odoo 17How to Make a Field read-only in Odoo 17
How to Make a Field read-only in Odoo 17Celine George
 

Último (20)

How to Send Emails From Odoo 17 Using Code
How to Send Emails From Odoo 17 Using CodeHow to Send Emails From Odoo 17 Using Code
How to Send Emails From Odoo 17 Using Code
 
P4C x ELT = P4ELT: Its Theoretical Background (Kanazawa, 2024 March).pdf
P4C x ELT = P4ELT: Its Theoretical Background (Kanazawa, 2024 March).pdfP4C x ELT = P4ELT: Its Theoretical Background (Kanazawa, 2024 March).pdf
P4C x ELT = P4ELT: Its Theoretical Background (Kanazawa, 2024 March).pdf
 
CHUYÊN ĐỀ DẠY THÊM TIẾNG ANH LỚP 11 - GLOBAL SUCCESS - NĂM HỌC 2023-2024 - HK...
CHUYÊN ĐỀ DẠY THÊM TIẾNG ANH LỚP 11 - GLOBAL SUCCESS - NĂM HỌC 2023-2024 - HK...CHUYÊN ĐỀ DẠY THÊM TIẾNG ANH LỚP 11 - GLOBAL SUCCESS - NĂM HỌC 2023-2024 - HK...
CHUYÊN ĐỀ DẠY THÊM TIẾNG ANH LỚP 11 - GLOBAL SUCCESS - NĂM HỌC 2023-2024 - HK...
 
CapTechU Doctoral Presentation -March 2024 slides.pptx
CapTechU Doctoral Presentation -March 2024 slides.pptxCapTechU Doctoral Presentation -March 2024 slides.pptx
CapTechU Doctoral Presentation -March 2024 slides.pptx
 
How to Create a Toggle Button in Odoo 17
How to Create a Toggle Button in Odoo 17How to Create a Toggle Button in Odoo 17
How to Create a Toggle Button in Odoo 17
 
DUST OF SNOW_BY ROBERT FROST_EDITED BY_ TANMOY MISHRA
DUST OF SNOW_BY ROBERT FROST_EDITED BY_ TANMOY MISHRADUST OF SNOW_BY ROBERT FROST_EDITED BY_ TANMOY MISHRA
DUST OF SNOW_BY ROBERT FROST_EDITED BY_ TANMOY MISHRA
 
Ultra structure and life cycle of Plasmodium.pptx
Ultra structure and life cycle of Plasmodium.pptxUltra structure and life cycle of Plasmodium.pptx
Ultra structure and life cycle of Plasmodium.pptx
 
AUDIENCE THEORY -- FANDOM -- JENKINS.pptx
AUDIENCE THEORY -- FANDOM -- JENKINS.pptxAUDIENCE THEORY -- FANDOM -- JENKINS.pptx
AUDIENCE THEORY -- FANDOM -- JENKINS.pptx
 
How to Show Error_Warning Messages in Odoo 17
How to Show Error_Warning Messages in Odoo 17How to Show Error_Warning Messages in Odoo 17
How to Show Error_Warning Messages in Odoo 17
 
KARNAADA.pptx made by - saransh dwivedi ( SD ) - SHALAKYA TANTRA - ENT - 4...
KARNAADA.pptx  made by -  saransh dwivedi ( SD ) -  SHALAKYA TANTRA - ENT - 4...KARNAADA.pptx  made by -  saransh dwivedi ( SD ) -  SHALAKYA TANTRA - ENT - 4...
KARNAADA.pptx made by - saransh dwivedi ( SD ) - SHALAKYA TANTRA - ENT - 4...
 
Work Experience for psp3 portfolio sasha
Work Experience for psp3 portfolio sashaWork Experience for psp3 portfolio sasha
Work Experience for psp3 portfolio sasha
 
How to Add Existing Field in One2Many Tree View in Odoo 17
How to Add Existing Field in One2Many Tree View in Odoo 17How to Add Existing Field in One2Many Tree View in Odoo 17
How to Add Existing Field in One2Many Tree View in Odoo 17
 
The basics of sentences session 10pptx.pptx
The basics of sentences session 10pptx.pptxThe basics of sentences session 10pptx.pptx
The basics of sentences session 10pptx.pptx
 
Easter in the USA presentation by Chloe.
Easter in the USA presentation by Chloe.Easter in the USA presentation by Chloe.
Easter in the USA presentation by Chloe.
 
Prescribed medication order and communication skills.pptx
Prescribed medication order and communication skills.pptxPrescribed medication order and communication skills.pptx
Prescribed medication order and communication skills.pptx
 
Riddhi Kevadiya. WILLIAM SHAKESPEARE....
Riddhi Kevadiya. WILLIAM SHAKESPEARE....Riddhi Kevadiya. WILLIAM SHAKESPEARE....
Riddhi Kevadiya. WILLIAM SHAKESPEARE....
 
Unveiling the Intricacies of Leishmania donovani: Structure, Life Cycle, Path...
Unveiling the Intricacies of Leishmania donovani: Structure, Life Cycle, Path...Unveiling the Intricacies of Leishmania donovani: Structure, Life Cycle, Path...
Unveiling the Intricacies of Leishmania donovani: Structure, Life Cycle, Path...
 
Vani Magazine - Quarterly Magazine of Seshadripuram Educational Trust
Vani Magazine - Quarterly Magazine of Seshadripuram Educational TrustVani Magazine - Quarterly Magazine of Seshadripuram Educational Trust
Vani Magazine - Quarterly Magazine of Seshadripuram Educational Trust
 
Personal Resilience in Project Management 2 - TV Edit 1a.pdf
Personal Resilience in Project Management 2 - TV Edit 1a.pdfPersonal Resilience in Project Management 2 - TV Edit 1a.pdf
Personal Resilience in Project Management 2 - TV Edit 1a.pdf
 
How to Make a Field read-only in Odoo 17
How to Make a Field read-only in Odoo 17How to Make a Field read-only in Odoo 17
How to Make a Field read-only in Odoo 17
 

Folic acid- Chemistry, One carbon metabolism and megaloblastic anemia

  • 1. Folic acid- Chemistry, functions and clinical significance Namrata Chhabra MHPE, MD, CMCL FAIMER FELLOW- REGIONAL INSTITUTION, Principal-in-charge, Professor& Head, Department of Biochemistry, SSR Medical College, Mauritius
  • 2. Learning Objectives • Structure of Folic acid • Sources, • Recommended Daily allowance, • Absorption, transportation, storage and excretion, • Functions and coenzyme role, • Biological and clinical significance of folic acid 10-Jul-21 Our Biochemistry 2
  • 3. Folic acid • Folate and folic acid are forms of a water-soluble B vitamin. • Folate occurs naturally in food, and folic acid is the synthetic form of this vitamin. • Synonyms: • Liver lactobacillus Caseifactor, • Vitamin M, • Streptococcus lactis R (SLR) factor, • Vitamin Bc, • Fermentation residue factor, and • Pteroyl glutamic acid (PGA) 10-Jul-21 Our Biochemistry 3
  • 4. Structure of Folic acid • A composite molecule • Made up of three parts: • A pteridine ring system (6- methylpterin), • Para-amino benzoic acid, and • Glutamic acid. 10-Jul-21 Our Biochemistry 4
  • 5. Chemical forms of folic acid • Monoglutamate (Vitamin Bc): Having one glutamic acid. • Triglutamate“fermentation factor”: Having three glutamic acid residues. • Heptaglutamate (vitamin Bc conjugate of yeast ): Having seven glutamate residues. 10-Jul-21 Our Biochemistry 5
  • 6. Role of structural components of folic acid • The glutamic acid doesn't participate in the coenzyme functions of folic acid. • Folic acid in the interior of the cell may contain a “chain” of three to eight glutamic acid residues, which serves as a negatively charged “handle” to keep the coenzyme inside cells and/or bound to the appropriate enzymes. • The pteridine portion of the coenzyme and the p-amino benzoic acid portion participate directly in the metabolic reactions of folate. 10-Jul-21 Our Biochemistry 6
  • 7. Sources of folic acid • Green leafy vegetables (such as spinach, broccoli, and lettuce), okra, asparagus, • Fruits (such as bananas, melons, and lemons)beans, yeast, mushrooms, • Meat (such as beef liver and kidney), • Orange juice, and tomato juice. • Many microorganisms including those inhabiting the intestinal tract can synthesize folic acid. 10-Jul-21 Our Biochemistry 7
  • 8. Recommended daily allowance (RDA) • Since 1998, as required by federal law, folic acid has been added to cold cereals, flour, breads, pasta, bakery items, cookies, and crackers. • Daily requirements of 50–100 mcg/d are usually met in the diet. • Total body stores of folate are approximately 5000 mcg, enough to supply requirements for 2–3 months. 10-Jul-21 Our Biochemistry 8
  • 9. Absorption of folic acid • Absorption occurs along the whole length of mucosa of small intestine. • Polyglutamates ingested in diet are converted to mono-glutamates • Dihydrofolates are reduced to tetrahydrofolates by folate reductase • Tetrahydrofolates are then converted to methyl tetrahydrofolates, which enter the portal blood and then carried to liver. • Conjugases (γ-glutamyl carboxypeptidases) in the intestinal lumen cleave off extra glutamic acid residues before absorption of folate in the small intestine. 10-Jul-21 Our Biochemistry 9
  • 10. Transportation, plasma and tissue levels • Transportation-Folate is transported in blood as methyl tetrahydrofolate bound to a specific protein. • Plasma level: In normal individuals, it varies from 3 to 21 ng/ml. • Tissue folate: About 70 mg in the whole body, of which about 1/3 (5 to 15 μg/g) is in the liver. • RB cells folate: Folate is incorporated into the RB cells during erythropoiesis and is retained there during their entire life span. • Red cell folate is a reliable indicator of the folate status of the body. • Average level is 300 ng/ml of whole blood (range 160–640 ng/ml). 10-Jul-21 Our Biochemistry 10
  • 11. Excretion of folate • Urine: 2 to 5 μg/day. • Excretion is much increased after an oral dose of folate if the tissues are saturated. • Feces contain 20 per cent of the ingested folates that remains unabsorbed and some unabsorbed synthesis of folate by bacterial flora of intestine. 10-Jul-21 Our Biochemistry 11
  • 12. Activation of folic acid • Folic acid, before functioning as a coenzyme, must be reduced first to 7, 8-dihydrofolic acid(F.H2) and then to 5, 6, 7, 8 tetrahydrofolate (F.H4). • Both the reactions are catalyzed by Folic acid reductases enzyme, which use NADPH as hydrogen donor. • This enzyme also requires vitamin C (ascorbic acid) as a cofactor. 10-Jul-21 Our Biochemistry 12
  • 13. Biologically active forms of folic acid Active “coenzyme” form of the vitamin is the reduced tetrahydro derivative, Tetrahydrofolate F.H4, obtained by addition of four hydrogens to the pteridine moiety at 5, 6, 7 and 8 position. The other forms occur only in small quantities. 10-Jul-21 Our Biochemistry 13
  • 14. Functions of folic acid • One carbon metabolism-Folates act as coenzymes in the transfer of single-carbon units. • Replication and Transcription- Folate is involved in purine and pyrimidine synthesis required for DNA and RNA synthesis. • Folate is also a coenzyme for methionine synthesis, in which Methylcobalamine is also involved. 10-Jul-21 Our Biochemistry 14
  • 15. One carbon compounds • One carbon moiety (C1) may be either: • Methyl (–CH3), • Formyl (–CHO), • Formate (H.COOH), • Formimino group (–CH=NH) or • Hydroxymethyl (–CH2OH). • Most of them are metabolically “interconvertible” 10-Jul-21 Our Biochemistry 15
  • 16. Sources of one carbon fragments • One carbon fragments are produced by the metabolism of : • Serine • Glycine • Tryptophan • Histidine, and • Choline 10-Jul-21 Our Biochemistry 16
  • 17. Utilization of one carbon fragments • Methylene-, methenyl-, and 10-formyl- tetrahydrofolates are interconvertible. • The methylene form donates its methyl group during the biosynthesis of thymidine nucleotides for DNA synthesis, • the methenyl form donates its group as a Formyl group during purine biosynthesis, and • the methyl form is the donor of the methyl group to sulfur during methionine formation. • When one-carbon folates are not required, the oxidation of formyl- tetrahydrofolate to yield carbon dioxide provides a means of maintaining a pool of free folate. 10-Jul-21 Our Biochemistry 17
  • 18. Role of folic acid in nucleotide synthesis • Two different forms of folate are required for different aspects of nucleotide biosynthesis. • N10-formyl THF provides the C-2 and C-8 carbons for the de novo synthesis of purine rings, and thus is critical for DNA metabolism. 10-Jul-21 Our Biochemistry 18
  • 19. Role of folic acid in nucleotide synthesis • The Methylene form, N5,N10- methylene THF, is required for the production of dTMP from dUMP. • Methotrexate, inhibits dihydrofolate reductase and has been exploited as an anti-cancer 10-Jul-21 Our Biochemistry 19
  • 20. Role of folic acid in Trans Methylation reactions and Folate trap • In the absence of B12, THF can be trapped in the N5-methyl THF form and thus be removed from the THF pool. This is referred to as the “methyl trap,” which can impact other areas of 1-carbon metabolism, such as dTMP production. 10-Jul-21 Our Biochemistry 20
  • 21. Summary of functions of folic acid 10-Jul-21 Our Biochemistry 21
  • 22. Folate antagonists • 1) Sulfanilamide is the simplest of the sulfa drugs, used as antibacterial agents. • Because of structural similarity to p- aminobenzoic acid, sulfanilamide inhibits the growth of bacteria by interfering with their ability to use p-aminobenzoic acid to synthesize folic acid. • Because humans don't make folic acid, sulfanilamide is not toxic to humans in the doses that inhibit bacteria. 10-Jul-21 Our Biochemistry 22
  • 23. Folate antagonists 2) Trimethoprim and Pyrimethamine • The dihydrofolate reductases of some bacteria and parasites differ from the human enzyme; • Inhibitors of these enzymes can be used as antibacterial drugs (e.g., trimethoprim) and Antimalarial drugs (e.g., pyrimethamine). 10-Jul-21 Our Biochemistry 23
  • 24. Folate antagonists used as anti cancer drugs 1) Methotrexate, an analog of 10-methyl-tetrahydrofolate, inhibits dihydrofolate reductase and has been exploited as an anti-cancer 2) Aminopterin is also an inhibitor of DHFR enzyme and is used as an anticancer drug. 3) Trimetrexate, Lometrexol and Pemetrexed are also some of the upcoming folate antagonists used in cancer chemotherapy. 10-Jul-21 Our Biochemistry 24
  • 25. Leucovorin (LV) • Leucovorin (LV) is a form of folic acid that can help "rescue" or reverse the toxic effects of methotrexate. • LV is not a folate antagonist per se, but the folate derivative 5- formyltetrahydrofolate. • N5-formyl THF is normally administered 24 hours following treatment with methotrexate; • It can be converted to THF by these normal cells by bypassing the block caused by methotrexate. • Therefore, these normal cells can synthesize deoxy thymidine and carry out DNA synthesis. 10-Jul-21 Our Biochemistry 25
  • 26. Megaloblastic anemia due to folate deficiency • Inadequate dietary intake. • Alcoholics, anorectic patients, persons who do not eat fresh fruits and vegetables, and those who overcook their food are candidates for folate deficiency. • Drugs such as phenytoin, trimethoprim-sulfamethoxazole, or Sulfasalazine may interfere with folate absorption. • Folic acid requirements are increased in pregnancy, hemolytic anemia, and exfoliative skin disease, and in these cases the increased requirements (five to ten times normal) may not be met by a normal diet. • Patients with increased folate requirements should receive supplementation with 1 mg/d of folic acid. 10-Jul-21 Our Biochemistry 26
  • 27. Biochemical Basis of Megaloblastic Anemia • The common feature of all megaloblastic anemias is a defect in DNA synthesis that affects rapidly dividing cells in the bone marrow. • In deficiencies of either folate or cobalamin, there is failure to convert deoxy uridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP), the precursor of dTTP. • This is because folate is needed as the coenzyme 5, 10-methylene- THF polyglutamate for conversion of dUMP to dTMP; the availability of 5, 10-methylene-THF is reduced in either cobalamin or folate deficiency. 10-Jul-21 Our Biochemistry 27
  • 28. Clinical manifestations • History: • The patient's history is important because it may reveal the underlying disorder. • Very often, a patient presents with a history of excessive alcohol intake with concurrent poor diet intake. • Other times, patients may be pregnant or lactating; • may take certain drugs, such as phenytoin, sulfonamides, or methotrexate; • may have chronic hemolytic anemia; or • may have underlying malabsorption. 10-Jul-21 Our Biochemistry 28
  • 29. Clinical manifestations 2.Oral lesions • Some patients complain of a sore tongue or pain upon swallowing. • The tongue may appear swollen, beefy, red, or shiny, usually around the edges and tips initially. • Angular stomatitis also may be observed. • These oral lesions typically occur at the time when folate depletion is severe enough to cause megaloblastic anemia, although, occasionally, lesions may occur before the anemia 10-Jul-21 Our Biochemistry 29
  • 30. Clinical manifestations • GI symptoms • Patients may present with GI symptoms, such as nausea, vomiting, abdominal pain, and diarrhea, especially after meals. • Anorexia also is common and, in combination with the above symptoms, may lead to marked weight loss. 10-Jul-21 Our Biochemistry 30
  • 31. Clinical manifestations • 4. Hyperpigmentation • Patients with folate deficiency may have darkening of the skin and mucous membranes, particularly at the dorsal surfaces of the fingers, toes, and creases of palms and soles. • Distribution typically is patchy. • The hyperpigmentation gradually should resolve after weeks or months of folate treatment. • A modest temperature elevation (<102°F) is common in patients who are folate deficient, despite the absence of any infection. 10-Jul-21 Our Biochemistry 31
  • 32. Laboratory Investigations • Serum folate (reference range 2.5-20 ng/mL) and serum cobalamin (reference range 200-900 pg/mL) • Ruling out cobalamin deficiency is very important because folate treatment will not improve neurologic abnormalities due to cobalamin deficiency. • Additional follow-up tests include serum homocysteine (reference range 5- 16 mmol/L), which is elevated in B-12 and folate deficiency, and serum methylmalonic acid (reference range 70-270 mmol/L), which is elevated in B-12 deficiency only. • Red blood cell folate levels (reference range >140 ng/mL) tend to reflect chronic folate status rather than acute changes in folate that are reflected in serum folate levels, 10-Jul-21 Our Biochemistry 32
  • 33. Laboratory Investigations • Hematological Findings • Peripheral Blood film • Oval macrocytes, usually with considerable anisocytosis and poikilocytosis, are the main feature. • The MCV is usually >100 fL unless a cause of microcytosis (e.g., iron deficiency or thalassemia trait) is present. • Some of the neutrophils are hyper segmented (more than five nuclear lobes). • There may be leucopenia due to a reduction in granulocytes and lymphocytes, but this is usually >1.5 x 109/L; • the platelet count may be moderately reduced, rarely to <40 x 109/L. • The severity of all these changes parallels the degree of anemia. 10-Jul-21 Our Biochemistry 33
  • 34. Laboratory Investigations • Bone Marrow • Bone marrow morphology is characteristically abnormal. • Marked erythroid hyperplasia is present as a response to defective red blood cell production (ineffective erythropoiesis). • Megaloblastic changes in the erythroid series include abnormally large cell size and asynchronous maturation of the nucleus and cytoplasm—i.e., cytoplasmic maturation continues while impaired DNA synthesis causes retarded nuclear development. • In the myeloid series, giant metamyelocytes are characteristically seen 10-Jul-21 Our Biochemistry 34
  • 35. Treatment • Oral doses of 5–15 mg folic acid daily are satisfactory. • It is customary to continue therapy for about 4 months, when all folate- deficient red cells will have been eliminated and replaced by new folate- replete populations. • Cobalamin deficiency must be excluded and, if present, corrected, otherwise cobalamin neuropathy may develop, despite a response of the anemia of cobalamin deficiency to folate therapy. • Long-term folic acid therapy is required when the underlying cause of the deficiency cannot be corrected, and the deficiency is likely to recur. • In any patient receiving long-term folic acid therapy, it is important to measure the serum cobalamin level at regular (e.g., once yearly) intervals to exclude the coincidental development of cobalamin deficiency. 10-Jul-21 Our Biochemistry 35
  • 36. Therapeutic significance of folate supplementation • Folic acid is used for preventing and treating low blood levels of folate (folate deficiency) and high blood levels of homocysteine (Hyperhomocysteinemia). • Women who are pregnant or might become pregnant take folic acid to prevent miscarriage and "neural tube defects "such as spina bifida. • Folic acid is also used for many other conditions including depression, stroke, decline in memory and thinking skills in older people 10-Jul-21 Our Biochemistry 36
  • 37. Summary • A composite molecule, made up of three parts :a pteridine ring system, para-amino benzoic acid, and glutamic acid. • Daily requirement is 50–100 mcg/d. • Total body stores of folate are approximately 5000 mcg. • Participates in one carbon metabolism, nucleotide biosynthesis and as a coenzyme for methionine synthesis. • In the absence of B12, THF can be trapped in the N5-methyl THF form. • Folate antagonists act as antibiotics and anticancer drugs. • Folate deficiency causes megaloblastic anemia. 10-Jul-21 Our Biochemistry 37
  • 38. Thank you 10-Jul-21 Our Biochemistry 38