orotate

Three steps

• 5-hydroxyisourateReach from here →
  1. orotate(out) + nicotinate(in) = orotate(in) + nicotinate(out)
  2. nicotinate(in) + urate(out) = nicotinate(out) + urate(in)
  3. urate:oxygen oxidoreductase

  Catalysed by SLC22A12, SLC22A13inner side of the membrane, outer side of the membrane, cytosol

• NAADPHReach from here →
  1. orotate(out) + nicotinate(in) = orotate(in) + nicotinate(out)
  2. nicotinate + NADP(+) = NAADP(+) + nicotinamide
  3. NAADPH + O2 + H(+) = NAADP(+) + H2O2

  Catalysed by SLC22A12, CD38, DUOX2, DUOX1inner side of the membrane, outer side of the membraneOne of 3 routes

• a dicarboxylateReach from here →
  1. orotate(out) + nicotinate(in) = orotate(in) + nicotinate(out)
  2. nicotinate(in) + urate(out) = nicotinate(out) + urate(in)
  3. urate(out) + a dicarboxylate(in) = urate(in) + a dicarboxylate(out)

  Catalysed by SLC22A12, SLC22A13, SLC22A6inner side of the membrane, outer side of the membraneOne of 2 routes

• a thiolReach from here →
  1. orotate(out) + a carboxylate(in) = orotate(in) + a carboxylate(out)
  2. a thioester + H2O = a thiol + a carboxylate + H(+)
  3. a thioester + H2O = a thiol + a carboxylate + H(+)

  Catalysed by SLC22A13, PNKDinner side of the membrane, outer side of the membrane

• quinolinateReach from here →
  1. orotate(out) + nicotinate(in) = orotate(in) + nicotinate(out)
  2. 5-phospho-alpha-D-ribose 1-diphosphate + nicotinate + ATP + H2O = nicotinate beta-D-ribonucleotide + ADP + phosphate + diphosphate
  3. nicotinate beta-D-ribonucleotide + CO2 + diphosphate = quinolinate + 5-phospho-alpha-D-ribose 1-diphosphate + 2 H(+)

  Catalysed by SLC22A12, NAPRT, QPRTinner side of the membrane, outer side of the membrane

• L-aspartateReach from here →
  1. (S)-dihydroorotate + a quinone = orotate + a quinol
  2. (S)-dihydroorotate amidohydrolase
  3. carbamoyl-phosphate:L-aspartate carbamoyltransferase

  Catalysed by DHODH, CADcytosolOne of 2 routes

• an alcoholReach from here →
  1. orotate(out) + a carboxylate(in) = orotate(in) + a carboxylate(out)
  2. a carboxylic ester + H2O = an alcohol + a carboxylate + H(+)
  3. a carboxylic ester + H2O = an alcohol + a carboxylate + H(+)

  Catalysed by SLC22A13, CES2, CES1, CES5A and 2 moreinner side of the membrane, outer side of the membrane

• glutarateReach from here →
  1. orotate(out) + nicotinate(in) = orotate(in) + nicotinate(out)
  2. nicotinate(in) + urate(out) = nicotinate(out) + urate(in)
  3. urate(in) + glutarate(out) = urate(out) + glutarate(in)

  Catalysed by SLC22A12, SLC22A13, SLC22A8inner side of the membrane, outer side of the membraneOne of 2 routes

• beta-D-fructose 1,6-bisphosphateReach from here →
  1. (S)-dihydroorotate + a quinone = orotate + a quinol
  2. a quinone + sn-glycerol 3-phosphate = dihydroxyacetone phosphate + a quinol
  3. beta-D-fructose 1,6-bisphosphate = D-glyceraldehyde 3-phosphate + dihydroxyacetone phosphate

  Catalysed by DHODH, GPD2, ALDOA, ALDOB and 1 more

• thiosulfateReach from here →
  1. (S)-dihydroorotate + a quinone = orotate + a quinol
  2. a quinone + succinate = fumarate + a quinol
  3. transport of fumarate and thiosulfate (cytosol to mitochondria)

  Catalysed by DHODH, SDHB, SLC25A10mitochondrial matrix, cytosolOne of 3 routes

• D-ribose 1-phosphateReach from here →
  1. (S)-dihydroorotate + a quinone = orotate + a quinol
  2. 1-(beta-D-ribofuranosyl)-1,4-dihydronicotinamide + a quinone + H(+) = beta-nicotinamide D-riboside + a quinol
  3. purine nucleoside phosphorylase (nicotinamide)

  Catalysed by DHODH, NQO2, PNPcytosol

• (S)-lactic acidReach from here →
  1. orotate(out) + nicotinate(in) = orotate(in) + nicotinate(out)
  2. nicotinate(in) + urate(out) = nicotinate(out) + urate(in)
  3. transport of L-lactate and urate (cytosol to extracellular)

  Catalysed by SLC22A12, SLC22A13inner side of the membrane, outer side of the membrane, extracellular space, cytosol

• 1-(beta-D-ribofuranosyl)-1,4-dihydronicotinamideReach from here →
  1. (S)-dihydroorotate + a quinone = orotate + a quinol
  2. a quinol + 2 Fe(III)-[cytochrome c](out) = a quinone + 2 Fe(II)-[cytochrome c](out) + 2 H(+)(out)
  3. 1-(beta-D-ribofuranosyl)-1,4-dihydronicotinamide + a quinone + H(+) = beta-nicotinamide D-riboside + a quinol

  Catalysed by DHODH, CYC1, UQCRFS1, NQO2outer side of the membraneOne of 2 routes

• 2-(N(omega)-L-arginino)succinateReach from here →
  1. (S)-dihydroorotate + a quinone = orotate + a quinol
  2. a quinone + succinate = fumarate + a quinol
  3. 2-(Nomega-L-arginino)succinate arginine-lyase (fumarate-forming)

  Catalysed by DHODH, SDHB, ASLcytosolOne of 2 routes

• a 1-acylglycerone 3-phosphateReach from here →
  1. (S)-dihydroorotate + a quinone = orotate + a quinol
  2. a quinone + sn-glycerol 3-phosphate = dihydroxyacetone phosphate + a quinol
  3. dihydroxyacetone phosphate + an acyl-CoA = a 1-acylglycerone 3-phosphate + CoA

  Catalysed by DHODH, GPD2, GNPAT

• N(6)-(1,2-dicarboxyethyl)-AMPReach from here →
  1. (S)-dihydroorotate + a quinone = orotate + a quinol
  2. a quinone + succinate = fumarate + a quinol
  3. N6-(1,2-dicarboxyethyl)AMP AMP-lyase (fumarate-forming)

  Catalysed by DHODH, SDHB, ADSL, TNRC6BcytosolOne of 2 routes

• glutathioneReach from here →
  1. (S)-dihydroorotate + a quinone = orotate + a quinol
  2. a quinone + hydrogen sulfide + glutathione + H(+) = S-sulfanylglutathione + a quinol
  3. S-sulfanylglutathione + O2 + H2O = sulfite + glutathione + 2 H(+)

  Catalysed by DHODH, SQOR, ETHE1One of 3 routes

• 6-phospho-D-glucono-1,5-lactoneReach from here →
  1. orotate(out) + nicotinate(in) = orotate(in) + nicotinate(out)
  2. nicotinate + NADP(+) = NAADP(+) + nicotinamide
  3. NAADP(+) + D-glucose 6-phosphate = NAADPH + 6-phospho-D-glucono-1,5-lactone + H(+)

  Catalysed by SLC22A12, CD38, G6PDinner side of the membrane, outer side of the membrane

• 5-phospho-alpha-D-ribose 1-diphosphateReach from here →
  1. orotate(out) + nicotinate(in) = orotate(in) + nicotinate(out)
  2. 5-phospho-alpha-D-ribose 1-diphosphate + nicotinate + ATP + H2O = nicotinate beta-D-ribonucleotide + ADP + phosphate + diphosphate
  3. nicotinate beta-D-ribonucleotide + CO2 + diphosphate = quinolinate + 5-phospho-alpha-D-ribose 1-diphosphate + 2 H(+)

  Catalysed by SLC22A12, NAPRT, QPRTinner side of the membrane, outer side of the membraneOne of 2 routes

• carbamoyl phosphateReach from here →
  1. (S)-dihydroorotate + a quinone = orotate + a quinol
  2. (S)-dihydroorotate amidohydrolase
  3. carbamoyl-phosphate:L-aspartate carbamoyltransferase

  Catalysed by DHODH, CADcytosolOne of 2 routes

• 1-hexadecanoylglycerone 3-phosphateReach from here →
  1. (S)-dihydroorotate + a quinone = orotate + a quinol
  2. a quinone + sn-glycerol 3-phosphate = dihydroxyacetone phosphate + a quinol
  3. dihydroxyacetone phosphate + hexadecanoyl-CoA = 1-hexadecanoylglycerone 3-phosphate + CoA

  Catalysed by DHODH, GPD2, GNPAT

• trans-4-hydroxy-L-prolineReach from here →
  1. (S)-dihydroorotate + a quinone = orotate + a quinol
  2. a quinol + 2 Fe(III)-[cytochrome c](out) = a quinone + 2 Fe(II)-[cytochrome c](out) + 2 H(+)(out)
  3. trans-4-hydroxy-L-proline + a quinone = (3R,5S)-1-pyrroline-3-hydroxy-5-carboxylate + a quinol + H(+)

  Catalysed by DHODH, CYC1, UQCRFS1, PRODH2outer side of the membraneOne of 2 routes

• deamido-NAD(+)Reach from here →
  1. orotate(out) + nicotinate(in) = orotate(in) + nicotinate(out)
  2. 5-phospho-alpha-D-ribose 1-diphosphate + nicotinate + ATP + H2O = nicotinate beta-D-ribonucleotide + ADP + phosphate + diphosphate
  3. nicotinate beta-D-ribonucleotide + ATP + H(+) = deamido-NAD(+) + diphosphate

  Catalysed by SLC22A12, NAPRT, NMNAT3, NMNAT2 and 1 moreinner side of the membrane, outer side of the membrane

• (2S)-2-[5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamido]succinateReach from here →
  1. (S)-dihydroorotate + a quinone = orotate + a quinol
  2. a quinone + succinate = fumarate + a quinol
  3. 1-(5'-Phosphoribosyl)-5-amino-4-(N-succinocarboxamide)-imidazole AMP-lyase

  Catalysed by DHODH, SDHB, ADSLcytosolOne of 2 routes

• beta-D-ribosylnicotinateReach from here →
  1. orotate(out) + nicotinate(in) = orotate(in) + nicotinate(out)
  2. 5-phospho-alpha-D-ribose 1-diphosphate + nicotinate + ATP + H2O = nicotinate beta-D-ribonucleotide + ADP + phosphate + diphosphate
  3. beta-D-ribosylnicotinate + ATP = nicotinate beta-D-ribonucleotide + ADP + H(+)

  Catalysed by SLC22A12, NAPRT, NMRK2, NMRK1inner side of the membrane, outer side of the membrane

• D-glyceraldehyde 3-phosphateReach from here →
  1. (S)-dihydroorotate + a quinone = orotate + a quinol
  2. a quinone + sn-glycerol 3-phosphate = dihydroxyacetone phosphate + a quinol
  3. D-glyceraldehyde 3-phosphate = dihydroxyacetone phosphate

  Catalysed by DHODH, GPD2, TPI1

• an L-alpha-amino acidReach from here →
  1. orotate(out) + a carboxylate(in) = orotate(in) + a carboxylate(out)
  2. an N-acyl-L-amino acid + H2O = an L-alpha-amino acid + a carboxylate
  3. an N-acyl-L-amino acid + H2O = an L-alpha-amino acid + a carboxylate

  Catalysed by SLC22A13, ACY1, PM20D1inner side of the membrane, outer side of the membrane

• L-prolineReach from here →
  1. (S)-dihydroorotate + a quinone = orotate + a quinol
  2. a quinol + 2 Fe(III)-[cytochrome c](out) = a quinone + 2 Fe(II)-[cytochrome c](out) + 2 H(+)(out)
  3. L-proline + a quinone = (S)-1-pyrroline-5-carboxylate + a quinol + H(+)

  Catalysed by DHODH, CYC1, UQCRFS1, PRODH and 1 moreouter side of the membraneOne of 4 routes

• CHEBI:730073Reach from here →
  1. orotate(out) + nicotinate(in) = orotate(in) + nicotinate(out)
  2. nicotinate(in) + urate(out) = nicotinate(out) + urate(in)
  3. Peroxidase

  Catalysed by SLC22A12, SLC22A13, MPOinner side of the membrane, outer side of the membrane, nucleusOne of 3 routes

• 2'-phospho-cyclic ADP-riboseReach from here →
  1. orotate(out) + nicotinate(in) = orotate(in) + nicotinate(out)
  2. nicotinate + NADP(+) = NAADP(+) + nicotinamide
  3. 2'-phospho-cyclic ADP-ribose + nicotinate = NAADP(+)

  Catalysed by SLC22A12, CD38inner side of the membrane, outer side of the membrane

• alpha-NAD(+)Reach from here →
  1. orotate(out) + nicotinate(in) = orotate(in) + nicotinate(out)
  2. nicotinate + NADP(+) = NAADP(+) + nicotinamide
  3. alpha-NAD(+) + H2O = ADP-D-ribose + nicotinamide + H(+)

  Catalysed by SLC22A12, CD38, MACROD2, ADPRH and 3 moreinner side of the membrane, outer side of the membrane

• an aromatic L-alpha-amino acidReach from here →
  1. orotate(out) + a carboxylate(in) = orotate(in) + a carboxylate(out)
  2. an N-acyl-aromatic L-alpha-amino acid + H2O = an aromatic L-alpha-amino acid + a carboxylate
  3. an N-acyl-aromatic L-alpha-amino acid + H2O = an aromatic L-alpha-amino acid + a carboxylate

  Catalysed by SLC22A13, PM20D1, ACY3inner side of the membrane, outer side of the membrane