Health care

1. B A S A L I N G A P P A B G
D M L T . , B M L T . , B S B T . ,
M . S C . M E D I C A L B I O C H E M I S T R Y
D E P ' T O F B I O C H E M I S T R Y
J S S M E D I C A L C O L L E G E
One Carbon Metabolism

2. FOLIC ACID
 Folic acid (or folate), which plays a key role in one-
carbon metabolism, is essential for the
biosynthesis of several compounds.
 Chemically folic acid is pteroyl-glutamic acid made
up of pteridne nucleus- amino benzoic acid
(PABA)and glutamic acid.
 The role of folic acid is that it acts as a carrier of
one carbon groups or moities required in
metabolism.

3.  Structure of folic acid is shown below. Chemically
called pteroyl glutamic acid (PGA).
 There are at least three chemically related
compounds of nutritional importance which occur in
natural products, all may be termed pteroyl
glutamates.

5. These three compounds differ only in the number of
glutamic acid residues attached to pteridine PABA
complex (pteroic acid).
Monoglutamate: Having one glutamic acid. It is
synonymous
with vitamin Bc.
• Triglutamate: Having three glutamic acid residues.
This substance once designated as “fermentation factor”.
• Heptaglutamate: Having seven glutamate
residues,synonymous with vitamin Bc conjugate of
yeast.Pteroyl glutamic acid is liberated from these
conjugates by enzymes called conjugases.

6. Biological “Active” Forms
 Active “coenzyme” form of the vitamin is the reduced
tetra hydrderivative,Tetrahydrofolate reductase
FH4, obtained by addition of four hydrogen's to the
pteridne moiety at 5, 6, 7 and 8 position.
 Structure of tetrahydrofolate is shown below.

7. Structure of tetrahydrofolate

8.  Folic acid is reduced by dihydrofolate reductase in
two steps:
 First to dihydrofolic acid (DHFA),also called
dihydrofolate and then converted to tetra
hydrofolate (THFA).
 The double bonds at N-atom 5 and 8 as shown in
above figure are reduced .

9. The one carbon groups are as
 Methyl (-CH3)
 Methylene (=CH2)
 Methenyl (=CH-)
 Formyl (-HCO)
 Formimino(-CH=NH-)
 Hydroxy methyl (-CH2 –OH).
 All these one carbon groups which are carried by
folic acid .

10. Sources of One Carbon
 Serine
 Glycine
 Histidine
 Tryptophan

13. Metabolism of one carbon metabolism
 One carbon metabolism is basically indicates that
there will be a donation of carbon atom in variety of
metabolic reaction.
 Some of metabolic reactions which will need to carry
out function in our body,so we need a C-atom ,and
that has to be donated ,so it is going to do that so
that will be done at tetrahydro folate(THF)

15.  Basically THF it carries a one carbon derivative and
that will be donated in some other metabolic
reactions.
 Here so the THF is also referred as vitB9, so there
are THF derivatives which are Participating in one
carbon metabolismon they have

16.  N10 –formyl THF (-CHO)
 N5 ,N10 Methyl THF (-CH=)
 N5 ,N10 Methylene THF (-CH2-)
 N5 –Methyl THF (-CH3)
 Now to THF in order to make all these have different
types of folate derivatives ,so we need again a
vitB6,vitB2 ,VitB12, So these are the other water
Soluble vitamins but they are necessary for the
THF,to get into all their derivatives.

17.  So now let us one carbon metabolism is go on in our
body ,what are reactions shunts or participating in
one carbon metabolism,
 So we get folate (from green leafy vegetables)usually
folate we get as polyglutamate from of folate and the
intestine and glutamates are removed and
monoglutamate are just fold is absorbed and once
its,in our body.
 It will be converted to dihydrofolate (DHF)by an
enzyme dihydrofolate reductase (DHFR).

18.  So now we are going to convert folate into
dihydrofolate by an enzyme DHFR.
Folate Dihydro folate reductase Dihydrofolate
Now the DHF is converted THF By the same enzyme
DHFR applies aspects for this methotrexate(Basically
it is a anticancer drug which is going to DHFR enzyme
there by converting folate into THF is decrease that s
all ,so anyway

19.  Now what happens to THF ,will interact by a seine
,SHMT(serine hydroxyl methoxy transferase)this
SHMT it needs PLP(pyridoxal phosphate ) as a
coenzyme(VitB6)this is needed to make THF
derivative.
 So SHMT while transferase is going to take a methyl
form serine and side chain methyl group ie attached
to hydroxyl group there,ie in the side chain,CH2 is
taken from serine .

20.  So this serine will be attached to the THF and the
compund that will get
 N5 ,N10 Methylene THF (-CH2-)and it will get
glycine .This is a reversible reaction.
THF serine
N5,N10 methylene THF Glycine

21. Once it get a N5 ,N10 methylene THF ,So it has three
fates here,
1. It will be used as a coenzyme by thymidilate
synthase enzyme,This TS Which is going to convert
dUMP (deoxy uridine monophosphate) into
TMP(Thymidilate monophosphate).
dUMP TMP

22.  HISTIDINE: It is a source of formimino group
during its catabolism and transfers this formimino
group to THFA resulting in N5 form imino THFA .
 N5 N10 methenyl THFA can also give raise to
formimino THFA as well as N5 formyl THFA.

24.  Tryptophan: Formate can directly form N5 formyl
THFA.
 It is a source of formate

25. UTILISATION OF ONE CARBON
Synthesis of methionine :
 Methyl group of methyl cobalmine (VitB12) is used
to synthesize methionine from homocysteine .The
methyl group which is donated by methyl tetra
hydro folate(MTHF).
 The methionine as SAM then donates this methyl
group in the synthesis of many important compunds
like
 Choline
 Creatine
 Epinephrine etc .

26. IS Cobalmine which leads to folate deficiency ?
Why because the methyl tetrahydrofolate is not
utilized so this called folate trap or methyl trap.

27. PURINE SYNTHESIS
 Ionisine monophosphate (IMP) synthesis mainly it
requires N5,N10 Methenyl tetrahydrofolate and
formyl tetrahydrofolate.
 AMP and GMP both are significantly symthesized
from IMP.
 Ultimately ATP and GTP These are formed from
AMP And GMP respectively which are required for
the DNA synthesis.

28. PYRIMIDINE SYNTHESIS
 Thymidilate (TMP)is synthesized from deoxy
uridilate using N5,N10 methylene THF.
 It is used in DNA synthesis.
 In this Process tetrahydrofolate is simultaneously
oxidised to dihydrofolate which must be reconverted
to THF for reuse

29. Formyl tRNA
 Formyl THF is required for the formation of formyl
methionine tRNA needed in Protein Synthesis in
Prokaryotes and Mitochondria.

31. Deficiency of folic acid
 Megaloblastic anaemia
 Homocystinuria
 Birth defect.
 FIGLU Excretion Test:
 Folate deficiency blocks the last step of histidine
breakdown or catabolism ,due to lack of
tetrahydrofolate (THF ).
 This results in the accumulation of
FIGLU(Formimino glutamate ) in the body, which
leads to increased excretion of FIGLU in urine.
 It is an Intermediate of Histidine metabolism

32. Inhibitors of Folic acid
 Sulphonamides.
 Trimethoprim
 Septran
 Methotrexate
 Pyrimethamine

33. References
 Text book of biochemistry – D M vasudevan,
 Text book of biochemistry- S K Guptha
 Illustrated biochemistry – Lippincott's
 Text book of biochemistry – Pankaja naik