Prolyl hydroxylase

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Prolyl hydroxylase (or procollagen-proline dioxygenase) is an enzyme involved in the production of collagen, acting to hydroxylate proline to hydroxyproline.

It requires vitamin C as a cofactor to keep Iron in the reduced state (Fe²⁺) but it is not stoichiometrically consumed.^[1] α-ketoglutarate serves as reducing agent.

Reaction: Proline + α-ketoglutarate + O₂ → 4-hydroxyproline + CO₂ + succinate

It is classified under EC 1.14.11.2.

The phenolic compound ethyl protocatechuate is a prolyl 4-hydroxylase inhibitor.^[2]

References

^ Myllylä, R.; Tuderman, L.; Kivirikko, K. I. (1977). "Mechanism of the prolyl hydroxylase reaction. 2. Kinetic analysis of the reaction sequence". European journal of biochemistry / FEBS 80 (2): 349–357. PMID 200425.
^ Wang, J.; Buss, J. L.; Chen, G.; Ponka, P.; Pantopoulos, K. (2002). "The prolyl 4-hydroxylase inhibitor ethyl-3,4-dihydroxybenzoate generates effective iron deficiency in cultured cells". FEBS Letters 529 (2–3): 309–312. DOI:10.1016/S0014-5793(02)03389-6. PMID 12372619.

External links

MeSH Prolyl+hydroxylase

This enzyme-related article is a stub. You can help Wikipedia by expanding it.

Oxidoreductases: dioxygenases, including steroid hydroxylases (EC 1.14)

1.14.11: 2-oxoglutarate

Prolyl hydroxylase - Lysyl hydroxylase

1.14.13: NADH or NADPH

Flavin-containing monooxygenase (FMO1, FMO2, FMO3, FMO4, FMO5) - Nitric oxide synthase (NOS1, NOS2, NOS3) - Cholesterol 7 alpha-hydroxylase - Methane monooxygenase - 3A4 - Lanosterol 14 alpha-demethylase

1.14.14: reduced flavin or flavoprotein

19A1 - 2D6 - 2E1

1.14.15: reduced iron-sulfur protein

11B1 - 11B2 - 11A1

1.14.16: reduced pteridine (BH4 dependent)

Phenylalanine hydroxylase - Tyrosine hydroxylase - Tryptophan hydroxylase

1.14.17: reduced ascorbate

Dopamine beta hydroxylase

1.14.18-19: other

Tyrosinase - Stearoyl-CoA desaturase-1

1.14.99 - miscellaneous

Cyclooxygenase - Heme oxygenase (HMOX1) - Squalene monooxygenase - 17A1 - 21A2

B
enzm
- 1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 10
- 11
- 13
- 14
- 15-18
2.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
2.7.10
2.7.11-12
3.1
- 2
- 3
- 4
- 5
- 6
- 7
3.1.3.48
3.4.21
- 22
- 23
- 24
4.1
- 2
- 3
- 4
- 5
- 6
5.1
- 2
- 3
- 4
- 99
6.1-3
- 4
- 5-6

Metabolism: amino acid metabolism · synthesis and catabolism enzymes (essential in CAPS)

K→acetyl-CoA

LYSINE→	Saccharopine dehydrogenase Glutaryl-CoA dehydrogenase

LEUCINE→	Branched chain aminotransferase Branched-chain alpha-keto acid dehydrogenase complex Isovaleryl coenzyme A dehydrogenase Methylcrotonyl-CoA carboxylase Methylglutaconyl-CoA hydratase 3-hydroxy-3-methylglutaryl-CoA lyase

TRYPTOPHAN→	Indoleamine 2,3-dioxygenase/Tryptophan 2,3-dioxygenase Arylformamidase Kynureninase 3-hydroxyanthranilate oxidase Aminocarboxymuconate-semialdehyde decarboxylase Aminomuconate-semialdehyde dehydrogenase

PHENYLALANINE→tyrosine→	(see below)

G→pyruvate
→citrate

glycine→serine→	Serine hydroxymethyltransferase Serine dehydratase glycine→creatine: Guanidinoacetate N-methyltransferase Creatine kinase

alanine→	Alanine transaminase

cysteine→	D-cysteine desulfhydrase

threonine→	L-threonine dehydrogenase

G→glutamate→
α-ketoglutarate


HISTIDINE→	Histidine ammonia-lyase Urocanate hydratase Formiminotransferase cyclodeaminase

proline→	Proline oxidase Pyrroline-5-carboxylate reductase 1-Pyrroline-5-carboxylate dehydrogenase/ALDH4A1 PYCR1

arginine→	Ornithine aminotransferase Ornithine decarboxylase Agmatinase

→alpha-ketoglutarate→TCA	Glutamate dehydrogenase

Other	cysteine+glutamate→glutathione: Gamma-glutamylcysteine synthetase Glutathione synthetase Gamma-glutamyl transpeptidase glutamate→glutamine: Glutamine synthetase Glutaminase

G→propionyl-CoA→
succinyl-CoA

VALINE→	Branched chain aminotransferase Branched-chain alpha-keto acid dehydrogenase complex Enoyl-CoA hydratase 3-hydroxyisobutyryl-CoA hydrolase 3-hydroxyisobutyrate dehydrogenase Methylmalonate semialdehyde dehydrogenase

ISOLEUCINE→	Branched chain aminotransferase Branched-chain alpha-keto acid dehydrogenase complex 3-hydroxy-2-methylbutyryl-CoA dehydrogenase

METHIONINE→	generation of homocysteine: Methionine adenosyltransferase Adenosylhomocysteinase regeneration of methionine: Methionine synthase/Homocysteine methyltransferase Betaine-homocysteine methyltransferase conversion to cysteine: Cystathionine beta synthase Cystathionine gamma-lyase

THREONINE→	Threonine aldolase

→succinyl-CoA→TCA	Propionyl-CoA carboxylase Methylmalonyl CoA epimerase Methylmalonyl-CoA mutase

G→fumarate


PHENYLALANINE→tyrosine→	Phenylalanine hydroxylase Tyrosine aminotransferase 4-Hydroxyphenylpyruvate dioxygenase Homogentisate 1,2-dioxygenase Fumarylacetoacetate hydrolase tyrosine→melanin: Tyrosinase

G→oxaloacetate


asparagine→aspartate→	Asparaginase/Asparagine synthetase Aspartate transaminase

M: MET

mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m

k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon

m(A16/C10),i(k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)

Protein: scleroproteins

Extracellular matrix

Collagen

Fibril forming	type I (COL1A1, COL1A2) · type II (COL2A1) · type III · type V (COL5A1, COL5A2, COL5A3) · COL24A1 · COL26A1

Other	FACIT: type IX (COL9A1, COL9A2, COL9A3) · type XII (COL12A1) · COL14A1 · COL16A1 · COL19A1 · COL20A1 · COL21A1 · COL22A1 basement membrane: type IV (COL4A1, COL4A2, COL4A3, COL4A4, COL4A5, COL4A6) multiplexin: COL15A1 · type XVIII (COL18A1, Endostatin) transmembrane: COL13A1 · COL17A1 · COL23A1 · COL25A1 other: type VI (COL6A1, COL6A2, COL6A3, COL6A5) · type VII (COL7A1) · type VIII (COL8A1, COL8A2) · type X (COL10A1) · type XI (COL11A1, COL11A2) · COL27A1 · COL28A1

Enzymes	Prolyl hydroxylase/Lysyl hydroxylase · Cartilage associated protein/Leprecan · ADAMTS2 · Procollagen peptidase · Lysyl oxidase

Tenascin

Tenascin C · Tenascin X

Laminin

alpha (LAMA1, LAMA2, LAMA3, LAMA4, LAMA5) · beta (LAMB1, LAMB2, LAMB3, LAMB4) · gamma (LAMC1, LAMC2, LAMC3)

Other

ALCAM · Elastin (Tropoelastin) · Vitronectin · FRAS1 · FREM2 · Decorin · FAM20C · ECM1 · Matrix gla protein · Tectorin (TECTA, TECTB)

Other

Keratin/Cytokeratin · Gelatin · Reticulin · Cartilage oligomeric matrix protein

see also diseases
B proteins: BY STRUCTURE: membrane, globular (en, ca, an), fibrous

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