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Pathway Description
Riboflavin Metabolism
Arabidopsis thaliana
Metabolic Pathway
Riboflavin, also known as vitamin B2, belongs to the class of organic compounds known as flavins. These are compounds containing a flavin (7,8-dimethyl-benzo[g]pteridine-2,4-dione) moiety, with a structure characterized by an isoalloaxzine tricyclic ring. Like the other B vitamins, it supports energy production by aiding in the metabolizing of fats, carbohydrates, and proteins. Riboflavin is an important component of the cofactors flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN). They act as electron carriers in a number of oxidation-reduction (redox) reactions involved in energy production and in numerous metabolic pathways including fatty acid metabolism, the citrate cycle, and the electron transport chain. Riboflavin metabolism in Arabidopsis thaliana takes place in the chloroplast and it includes two subpathways: purine metabolism and the pentose phosphate pathway. From purine metabolism, GTP is produced which is then catalyzed by GTP cyclohydrolase II to produce 2,5-diamino-6-(5-phospho-D-ribosylamino)pyrimidin-4(3H)-one which undergoes deamination to produce 5-amino-6-(5'-phosphoribosylamino)uracil and ammonia. 5-Amino-6-(5'-phosphoribosylamino)uracil gets reduced to 5-amino-6-(5-phospho-D-ribitylamino)uracil by a reductase, then 5-amino-6-(5-phospho-D-ribitylamino)uracil phosphatase removes the phosphate group from 5-amino-6-(5-phospho-D-ribitylamino)uracil to produce 5-amino-6-(1-D-ribitylamino)uracil. 5-Amino-6-(1-D-ribitylamino)uracil with L-3,4-dihydroxybutan-2-one-4-phosphate synthase then act as substrate in the reaction catalyzed by 5-amino-6-(D-ribitylamino)uracil butanedionetransferase to produce 6,7-dimethyl-8-(D-ribityl)lumazine, this which is synthesized to riboflavin and 5-amino-6-(1-D-ribitylamino)uracil. Riboflavin is then catalyzed by a riboflavin kinase to produce FMN. FMN can also get dephosphorylated back to riboflavin. In A. thaliana, FMN could also be produced by FAD nucleotidohydrolase.
References
Riboflavin Metabolism References
Hiltunen HM, Illarionov B, Hedtke B, Fischer M, Grimm B: Arabidopsis RIBA proteins: two out of three isoforms have lost their bifunctional activity in riboflavin biosynthesis. Int J Mol Sci. 2012 Oct 31;13(11):14086-105. doi: 10.3390/ijms131114086.
Pubmed: 23203051
Hedtke B, Alawady A, Albacete A, Kobayashi K, Melzer M, Roitsch T, Masuda T, Grimm B: Deficiency in riboflavin biosynthesis affects tetrapyrrole biosynthesis in etiolated Arabidopsis tissue. Plant Mol Biol. 2012 Jan;78(1-2):77-93. doi: 10.1007/s11103-011-9846-1. Epub 2011 Nov 13.
Pubmed: 22081402
Hasnain G, Frelin O, Roje S, Ellens KW, Ali K, Guan JC, Garrett TJ, de Crecy-Lagard V, Gregory JF 3rd, McCarty DR, Hanson AD: Identification and characterization of the missing pyrimidine reductase in the plant riboflavin biosynthesis pathway. Plant Physiol. 2013 Jan;161(1):48-56. doi: 10.1104/pp.112.208488. Epub 2012 Nov 13.
Pubmed: 23150645
Frelin O, Huang L, Hasnain G, Jeffryes JG, Ziemak MJ, Rocca JR, Wang B, Rice J, Roje S, Yurgel SN, Gregory JF 3rd, Edison AS, Henry CS, de Crecy-Lagard V, Hanson AD: A directed-overflow and damage-control N-glycosidase in riboflavin biosynthesis. Biochem J. 2015 Feb 15;466(1):137-45. doi: 10.1042/BJ20141237.
Pubmed: 25431972
Sa N, Rawat R, Thornburg C, Walker KD, Roje S: Identification and characterization of the missing phosphatase on the riboflavin biosynthesis pathway in Arabidopsis thaliana. Plant J. 2016 Dec;88(5):705-716. doi: 10.1111/tpj.13291. Epub 2016 Sep 17.
Pubmed: 27490826
Ogawa T, Yoshimura K, Miyake H, Ishikawa K, Ito D, Tanabe N, Shigeoka S: Molecular characterization of organelle-type Nudix hydrolases in Arabidopsis. Plant Physiol. 2008 Nov;148(3):1412-24. doi: 10.1104/pp.108.128413. Epub 2008 Sep 24.
Pubmed: 18815383
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