ASSIGNMENT 02

WHAT IS THE BIOSYNTHETIC PATHWAY OF

VITAMIN B2?
PHG-831

SUBMITTED TO:
MADAM FARAH MAZHAR
SUBMITED BY:
NORIN MEMON

DEPARTMENT OF PHARMACOGNOSY
 ABSTRACT
The document comprises of detailed
process of biosynthesis of Vitamin
B2(Riboflavin) along with its
importance in human Health.

BIOSYNTHESIS
OF VITAMIN B2

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INDEX
Sr. No Topic/Sub-topic Pg. No

1 Introduction 03

2 Importance 03

3 Health Benefits of Vitamin B2 03

4 Biosynthesis of vitamin B2 03-04

5 Schematic Diagram of Vitamin B2 05

6 References 06

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INTRODUCTION
Vitamin B2 aka; Riboflavin is a water soluble, yellow orange organic compound in the vitamin
B complex. It was first discovered in 1879 as a yellow pigment in milk. Plants and
microorganisms are able to synthesize riboflavin, but animals and humans get it in their diet from
plant food. Chemically it is a 7,8-dimethyl-10-riityl-isoalloxazine which consist of a flavin
isoalloxazine ring bonded to sugar side chain, Ribitol. It is the most stable vitamin but can be
radially destroyed by ultraviolet rays or sun light.
B2 is an essential vitamin and is required in many metabolic reactions. Major sources of B2 are
milk, leafy vegetables, whole grains, liver, egg white, cheese, fish, and meat. The recommended
daily intake of B2 is 1.8mg. Though the deficiency of B2 is not so obvious but it is so named as
Ariboflavinosis characterized cracking of skin at the corners of the mouth and fissuring of lips,
swollen red beefy tongue, corneal vascularization and sensitivity of eyes to light, itching and
scaling of the facial skin.
IMPORTANCE
Riboflavin is the central component of co-enzymes Flavin Adenine Dinucleotide and Flavin
Mono Nucleotide.
They play role in metabolism of fats, ketone bodies, carbohydrates proteins.
It is involved in the support of immune system and nervous system, formation of RBC, cell
production and activation of folate & pyridoxine (vitamin B6).
HEALTH BENEFITS OF VITAMIN B2
➢ Used in cancer Therapy
➢ Antioxidant
➢ Used in control of Malarial infection
➢ Anti-inflammatory and Anti-nociception
➢ Reduce the risk of Osteoporosis
➢ Boost immune system
➢ Decrease Risk of Cataract
➢ Decrease risk of PMS
➢ Reduce Migraine
➢ Reperfusion of oxidative injury.
BIOSYNTHESIS OF VITAMIN B2
The biosynthesis of riboflavin starts with the dephosphorylation of imidazole ring of GTP
followed by sequence of deamination, side chain reduction and dephosphorylation of the 4,5-
diaminopyrimidine to 5-amino -6-ribitylamino-2,4(1H,3H)-pyrimidinedione which is then
condensed with 3,4-dihydroxy-2-butanone 4-phosphate obtained from ribulose 5-phosphate
affords 6,7-dimethyl-8-ribityllumazine. Afterward dismutation of lumazine derivative takes
place which results in the formation of riboflavin.
The enzymes responsible for this whole process are categorized into 4 categories.
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 1) RibA (GTP cyclohydroxylase-II and 3,4-dihydroxybutanone-4-phosphate synthase)
2) RibB (Riboflavin Synthase)
3) RibG (Deaminase and Reductase)
4) RibH (Lumazine synthase)
Detailed steps of biosynthetic pathway of Vitamin B2 (Riboflavin)
The biosynthesis of vitamin B2 starts with GTP (Guanosine triphosphate), Comprises of a
sequence of De-phosphorylation & decarboxylation, cleavage, reduction, de-phosphorylation,
condensation and dismutation reactions. The details of each reaction are as under.
1. De-phosphorylation
In this step GTP is converted into 2, 5-diamino-6-ribosylamino-4(3H)-pyrimidinone
5’Phosphate by the action of GTP Cyclo-hydroxylase-II enzyme as it causes the opening
of Imidazole ring of GTP by the addition of 3 molecules of water (H2O) which in turn
results in the release of pyrophosphate (from GTP) and format anion (as a Rxn by product).
2. Deamination
2, 5-diamino-6-ribosylamino-4(3H)-pyrimidinone 5’Phosphate undergo deamination in
the presence of H2O catalyzed by diamino-hydroxyamino-phosphoribosyl-
aminopyrimidine deaminase which causes the removal of amino group present on the 2 nd
position of heterocyclic ring and results in the formation of 5-amino-6-rybosylamino-
2,4(1H,3H)-pyrimidinedione 5’phosphate.
3. Reduction
5-amino-6-rybosylamino-2,4(1H,3H)-pyrimidinedione 5’phosphate under goes reduction
in the presence of NADPH2 by the action of 5-amino-6(5-phosphoribosylamino)uracil
reductase which results in the reduction of 5-amino-6-rybosylamino-2,4(1H,3H)-
pyrimidinedione 5’phosphate to 5-amino-6-ribitylamino-2,4(1H,3H)pyrimidinedione
5’phosphate and oxidation of NADPH2 to NADP+.
4. De-phosphorylation
The 5-amino-6-ribitylamino-2,4(1H,3H)pyrimidinedione 5’phosphate undergoes De-
phosphorylation before the condensation reaction as the enzyme involved in the
condensation is specific to de-phosphorylated 5-amino-6-ribitylamino-2,4(1H,3H)-
pyrimidinedione which is produced by Phosphatase type enzyme yet not fully discovered.
5. Condensation reaction
In this step by the action of 6,7-dimethyl-8-ribityllumazine synthase, 6,7-dimethyl-8-
ribityllumazine is produced in the result of condensation of 5-amino-6-ribitylamino-
2,4(1H,3H) Pyrimidinedione with 3,4-dihydroxybutanone-4-phosphate (which is
produced from ribulose 5-phosphate by the action of 3,4-dihydroxybutanone-4-phosphate
synthase).
6. Dismutation
This is the final step of Riboflavin synthesis, where in the presence of riboflavin synthase
dismutation of 6,7 dimethyl-8-ribityllumazine is catalyzed and in the result along with the
Riboflavin, 5-amino-6-Ribityl amino-2,4(1H,3H) Pyrimidinone is also produced which is
later on recycled in the biosynthetic pathway.

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Schematics diagram of Biosynthesis of vitamin B2

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REFERECES.

1) Markus Birkenmeier, Susanne Neumann, Thorsten Ro¨der; Kinetic modelling of riboflavin

biosynthesis in Bacillus subtilis under production conditions; Biotechnol Lett; 18 January
2014.
2) Nittiya Suwannasom , Ijad Kao , Axel Pruß , Radostina Georgieva, and Hans Bäumler;
Riboflavin: The Health Benefits of a Forgotten Natural Vitamin; Int. J. Mol. Sci. 2020, 21,
950; 1-22.
3) Jan Velíšek and Karel Cejpek; Biosynthesis of Food Constituents: Vitamins. 2. Water-
Soluble Vitamins: Part 1 – a Review; Czech J. Food Sci. Vol. 25, No. 2: 49–64

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