(S)-dihydroorotate

Three steps

• L-threonineReach from here →
  1. (S)-dihydroorotate + a quinone = orotate + a quinol
  2. trans-4-hydroxy-L-proline + a quinone = (3R,5S)-1-pyrroline-3-hydroxy-5-carboxylate + a quinol + H(+)
  3. trans-4-hydroxy-L-proline(out) + L-threonine(in) + Na(+)(out) = trans-4-hydroxy-L-proline(in) + L-threonine(out) + Na(+)(in)

  Catalysed by DHODH, PRODH2, SLC1A4inner side of the membrane, outer side of the membraneOne of 2 routes

• beta-alanineReach from here →
  1. (S)-dihydroorotate amidohydrolase
  2. carbamoyl-phosphate:L-aspartate carbamoyltransferase
  3. L-aspartate 1-carboxy-lyase (beta-alanine-forming)

  Catalysed by CAD, GAD2cytosolOne of 2 routes

• L-alanineReach from here →
  1. (S)-dihydroorotate amidohydrolase
  2. carbamoyl-phosphate:L-aspartate carbamoyltransferase
  3. oxaloacetate + L-alanine = L-aspartate + pyruvate

  Catalysed by CAD, AGXT2cytosolOne of 5 routes

• L-asparagineReach from here →
  1. (S)-dihydroorotate amidohydrolase
  2. carbamoyl-phosphate:L-aspartate carbamoyltransferase
  3. L-aspartate:L-glutamine amido-ligase (AMP-forming)

  Catalysed by CAD, ASNScytosolOne of 2 routes

• N(4)-(beta-N-acetyl-D-glucosaminyl)-L-asparagineReach from here →
  1. (S)-dihydroorotate amidohydrolase
  2. carbamoyl-phosphate:L-aspartate carbamoyltransferase
  3. N(4)-(beta-N-acetyl-D-glucosaminyl)-L-asparagine + H2O = N-acetyl-beta-D-glucosaminylamine + L-aspartate + H(+)

  Catalysed by CAD, AGAcytosol

• L-phenylalanineReach from here →
  1. (S)-dihydroorotate amidohydrolase
  2. carbamoyl-phosphate:L-aspartate carbamoyltransferase
  3. L-aspartate(in) + L-phenylalanine(out) = L-aspartate(out) + L-phenylalanine(in)

  Catalysed by CAD, SLC7A13cytosol, inner side of the membrane, outer side of the membraneOne of 2 routes

• L-tyrosineReach from here →
  1. (S)-dihydroorotate amidohydrolase
  2. carbamoyl-phosphate:L-aspartate carbamoyltransferase
  3. L-tyrosine(out) + L-aspartate(in) = L-tyrosine(in) + L-aspartate(out)

  Catalysed by CAD, SLC7A13cytosol, inner side of the membrane, outer side of the membraneOne of 2 routes

• N(omega),N(omega)-dimethyl-L-arginineReach from here →
  1. (S)-dihydroorotate amidohydrolase
  2. carbamoyl-phosphate:L-aspartate carbamoyltransferase
  3. N(omega),N(omega)-dimethyl-L-arginine + oxaloacetate = 5-(3,3-dimethylguanidino)-2-oxopentanoate + L-aspartate

  Catalysed by CAD, AGXT2cytosol

• (2S)-2-[5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamido]succinateReach from here →
  1. (S)-dihydroorotate amidohydrolase
  2. carbamoyl-phosphate:L-aspartate carbamoyltransferase
  3. 1-(5-Phosphoribosyl)-5-amino-4-carboxyimidazole:L-aspartate ligase (ADP-forming)

  Catalysed by CAD, PAICScytosolOne of 2 routes

• S-sulfanylglutathioneReach 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. a quinone + hydrogen sulfide + glutathione + H(+) = S-sulfanylglutathione + a quinol

  Catalysed by DHODH, CYC1, UQCRFS1, SQORouter side of the membrane

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

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

• 3-sulfino-L-alanineReach from here →
  1. (S)-dihydroorotate amidohydrolase
  2. carbamoyl-phosphate:L-aspartate carbamoyltransferase
  3. transport of 3-sulfinoalanine and aspartate (cytosol to mitochondria)

  Catalysed by CAD, SLC25A12, SLC25A13cytosol, mitochondrial matrixOne of 4 routes

• (3R,5S)-1-pyrroline-3-hydroxy-5-carboxylateReach 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

• NAADP(+)Reach from here →
  1. (S)-dihydroorotate + a quinone = orotate + a quinol
  2. orotate(out) + nicotinate(in) = orotate(in) + nicotinate(out)
  3. nicotinate + NADP(+) = NAADP(+) + nicotinamide

  Catalysed by DHODH, SLC22A12, CD38inner side of the membrane, outer side of the membraneOne of 2 routes