acetoacetate

Three steps

• 4,8,12-trimethyltridecanoyl-CoAReach from here →
  1. Acetoacetate:CoA ligase (AMP-forming)
  2. 3-hydroxy-3-methylglutaryl-CoA synthase (acetoacetyl-CoA)
  3. propanoyl-CoA C-acyltransferase (3-ketopristanoyl-CoA)

  Catalysed by AACS, HMGCS1, ACAA1, MYO5Bcytosol, peroxisomeOne of 2 routes

• (2E)-glutaconyl-CoAReach from here →
  1. (3S)-3-hydroxy-3-methylglutaryl-CoA = acetoacetate + acetyl-CoA
  2. 3-hydroxy-3-methylglutarate + glutaryl-CoA = (3S)-3-hydroxy-3-methylglutaryl-CoA + glutarate
  3. glutaryl-CoA + O2 = (2E)-glutaconyl-CoA + H2O2

  Catalysed by HMGCL, HMGCLL1, SUGCT, ACOX1

• (6Z,9Z,12Z)-octadecatrienoyl-CoAReach from here →
  1. Acetoacetate:CoA ligase (AMP-forming)
  2. 3-hydroxy-3-methylglutaryl-CoA synthase (acetoacetyl-CoA)
  3. long-chain-fatty-acid-CoA ligase (gamma-linolenate)

  Catalysed by AACS, HMGCS1, SLC27A2, ACSL4 and 6 morecytosolOne of 7 routes

• acryloyl-CoAReach from here →
  1. transport of acetoacetate and propanoate (cytosol to extracellular)
  2. Propanoate:CoA ligase (AMP-forming)
  3. medium-chain acyl-CoA dehydrogenase (propanoyl-CoA)

  Catalysed by SLC16A4, SLC16A5, SLC16A7, SLC16A8 and 6 moreextracellular space, cytosol, mitochondrial matrix

• dodecanoyl-CoAReach from here →
  1. Acetoacetate:CoA ligase (AMP-forming)
  2. 3-hydroxy-3-methylglutaryl-CoA synthase (acetoacetyl-CoA)
  3. long-chain-fatty-acid-CoA ligase (lauric acid)

  Catalysed by AACS, HMGCS1, SLC27A2, ACSL4 and 6 morecytosolOne of 9 routes

• eicosanoyl-CoAReach from here →
  1. Acetoacetate:CoA ligase (AMP-forming)
  2. 3-hydroxy-3-methylglutaryl-CoA synthase (acetoacetyl-CoA)
  3. long-chain-fatty-acid-CoA ligase (eicosanoate)

  Catalysed by AACS, HMGCS1, SLC27A2, ACSL4 and 6 morecytosolOne of 12 routes

• itaconyl-CoAReach from here →
  1. Acetoacetate:CoA ligase (AMP-forming)
  2. 3-hydroxy-3-methylglutaryl-CoA synthase (acetoacetyl-CoA)
  3. Itaconate:CoA ligase (GDP-forming)

  Catalysed by AACS, HMGCS1, SUCLG1, SUCLG2 and 1 morecytosol, mitochondrial matrixOne of 4 routes

• (9Z,12Z)-octadecadienoyl-CoAReach from here →
  1. Acetoacetate:CoA ligase (AMP-forming)
  2. 3-hydroxy-3-methylglutaryl-CoA synthase (acetoacetyl-CoA)
  3. long-chain-fatty-acid-CoA ligase ((6Z,9Z)-octadecadienoic acid)

  Catalysed by AACS, HMGCS1, SLC27A2, ACSL4 and 6 morecytosolOne of 13 routes

• tetradecanoyl-CoAReach from here →
  1. Acetoacetate:CoA ligase (AMP-forming)
  2. 3-hydroxy-3-methylglutaryl-CoA synthase (acetoacetyl-CoA)
  3. long-chain-fatty-acid-CoA ligase (myristic acid)

  Catalysed by AACS, HMGCS1, SLC27A2, ACSL4 and 6 morecytosolOne of 11 routes

• octanoyl-CoAReach from here →
  1. Acetoacetate:CoA ligase (AMP-forming)
  2. 3-hydroxy-3-methylglutaryl-CoA synthase (acetoacetyl-CoA)
  3. Octanoyl-CoA:L-carnitine O-octanoyltransferase

  Catalysed by AACS, HMGCS1, CROTcytosol, mitochondrial matrixOne of 20 routes

• phytanoyl-CoAReach from here →
  1. Acetoacetate:CoA ligase (AMP-forming)
  2. 3-hydroxy-3-methylglutaryl-CoA synthase (acetoacetyl-CoA)
  3. phytanate-CoA ligase

  Catalysed by AACS, HMGCS1cytosolOne of 5 routes

• propanoyl-CoAReach from here →
  1. transport of acetoacetate and pyruvate (cytosol to mitochondria)
  2. (R)-3-amino-2-methylpropanoate + pyruvate = 2-methyl-3-oxopropanoate + L-alanine
  3. 2-methyl-3-oxopropanoate + NAD(+) + CoA + H2O = propanoyl-CoA + hydrogencarbonate + NADH + H(+)

  Catalysed by AGXT2, ALDH6A1mitochondrial matrix, cytosol

• octadecanoyl-CoAReach from here →
  1. Acetoacetate:CoA ligase (AMP-forming)
  2. 3-hydroxy-3-methylglutaryl-CoA synthase (acetoacetyl-CoA)
  3. long-chain-fatty-acid-CoA ligase (stearate)

  Catalysed by AACS, HMGCS1, SLC27A2, ACSL4 and 5 morecytosolOne of 15 routes

• prostaglandin E1Reach from here →
  1. transport of acetoacetate and pyruvate (cytosol to mitochondria)
  2. (S)-lactate + NAD(+) = pyruvate + NADH + H(+)
  3. prostaglandin E1(out) + 2 (S)-lactate(in) = prostaglandin E1(in) + 2 (S)-lactate(out)

  Catalysed by LDHA, LDHB, LDHC, LDHAL6A and 2 moremitochondrial matrix, cytosol, inner side of the membrane, outer side of the membraneOne of 2 routes

• prostaglandin I2Reach from here →
  1. transport of acetoacetate and L-lactate (cytosol to extracellular)
  2. Transport of 15-Keto-Prostaglandin F2A, Lactate Antiport
  3. Formation of Prostaglandin I2

  Catalysed by SLC16A4, SLC16A5, SLC16A7, SLC16A8 and 1 moreextracellular space, cytosol

• prostaglandin F2alphaReach from here →
  1. transport of acetoacetate and pyruvate (cytosol to mitochondria)
  2. (S)-lactate + NAD(+) = pyruvate + NADH + H(+)
  3. prostaglandin F2alpha(out) + 2 (S)-lactate(in) = prostaglandin F2alpha(in) + 2 (S)-lactate(out)

  Catalysed by LDHA, LDHB, LDHC, LDHAL6A and 2 moremitochondrial matrix, cytosol, inner side of the membrane, outer side of the membraneOne of 4 routes

• prostaglandin H2Reach from here →
  1. transport of acetoacetate and pyruvate (cytosol to mitochondria)
  2. (S)-lactate + NAD(+) = pyruvate + NADH + H(+)
  3. prostaglandin H2(out) + 2 (S)-lactate(in) = prostaglandin H2(in) + 2 (S)-lactate(out)

  Catalysed by LDHA, LDHB, LDHC, LDHAL6A and 2 moremitochondrial matrix, cytosol, inner side of the membrane, outer side of the membraneOne of 2 routes

• prostaglandin D2Reach from here →
  1. transport of acetoacetate and pyruvate (cytosol to mitochondria)
  2. (S)-lactate + NAD(+) = pyruvate + NADH + H(+)
  3. prostaglandin D2(out) + 2 (S)-lactate(in) = prostaglandin D2(in) + 2 (S)-lactate(out)

  Catalysed by LDHA, LDHB, LDHC, LDHAL6A and 2 moremitochondrial matrix, cytosol, inner side of the membrane, outer side of the membraneOne of 4 routes

• D-alanineReach from here →
  1. transport of acetoacetate and pyruvate (cytosol to mitochondria)
  2. (R)-3-Amino-2-methylpropanoate:pyruvate aminotransferase
  3. D-alanine(out) + L-alanine(in) = D-alanine(in) + L-alanine(out)

  Catalysed by AGXT2, SLC7A10mitochondrial matrix, cytosol, inner side of the membrane, outer side of the membraneOne of 2 routes

• (6R)-5,10-methenyltetrahydrofolateReach from here →
  1. transport of acetoacetate and formate (cytosol to extracellular)
  2. Formate:tetrahydrofolate ligase (ADP-forming)
  3. 5,10-Methenyltetrahydrofolate 5-hydrolase (decyclizing)

  Catalysed by SLC16A4, SLC16A5, MTHFD1extracellular space, cytosolOne of 2 routes

• (13S)-hydroperoxy-(9Z,11E)-octadecadienoateReach from here →
  1. transport of acetoacetate and L-lactate (cytosol to extracellular)
  2. (S)-Lactate:ferricytochrome-c 2-oxidoreductase
  3. 13(S)-HPODE to 13-oxy-radical-octadecadienoate conversion

  Catalysed by SLC16A4, SLC16A5, SLC16A7, SLC16A8 and 2 moreextracellular space, cytosol, mitochondrial matrix

• 2-(N(omega)-L-arginino)succinateReach from here →
  1. 4-fumarylacetoacetate + H2O = acetoacetate + fumarate + H(+)
  2. 4-fumarylacetoacetate fumarylhydrolase
  3. 2-(Nomega-L-arginino)succinate arginine-lyase (fumarate-forming)

  Catalysed by FAH, ASLcytosolOne of 2 routes

• N(6)-(1,2-dicarboxyethyl)-AMPReach from here →
  1. 4-fumarylacetoacetate + H2O = acetoacetate + fumarate + H(+)
  2. 4-fumarylacetoacetate fumarylhydrolase
  3. N6-(1,2-dicarboxyethyl)AMP AMP-lyase (fumarate-forming)

  Catalysed by FAH, ADSL, TNRC6BcytosolOne of 2 routes

• guanidinoacetateReach from here →
  1. transport of acetoacetate and formate (cytosol to extracellular)
  2. transport of chloride and formate (cytosol to extracellular)
  3. Transport of Guanidinoacetic Acid

  Catalysed by SLC16A4, SLC16A5, SLC26A4extracellular space, cytosol

• sphing-4-enineReach from here →
  1. Acetoacetate:CoA ligase (AMP-forming)
  2. 3-hydroxy-3-methylglutaryl-CoA synthase (acetoacetyl-CoA)
  3. acyl-CoA:sphingosine N-acyltransferase

  Catalysed by AACS, HMGCS1, ASAH1, ACER2 and 2 morecytosol, Golgi apparatusOne of 3 routes

• D-threonineReach from here →
  1. transport of acetoacetate and pyruvate (cytosol to mitochondria)
  2. (R)-3-Amino-2-methylpropanoate:pyruvate aminotransferase
  3. D-threonine(out) + L-alanine(in) = D-threonine(in) + L-alanine(out)

  Catalysed by AGXT2, SLC7A10mitochondrial matrix, cytosol, inner side of the membrane, outer side of the membraneOne of 2 routes

• N-acetyl-alpha-D-glucosamine 1-phosphateReach from here →
  1. transport of acetate and acetoacetate (cytosol to extracellular)
  2. N-acetyl-D-glucosamine 6-phosphate + H2O = D-glucosamine 6-phosphate + acetate
  3. N-acetyl-alpha-D-glucosamine 1-phosphate = N-acetyl-D-glucosamine 6-phosphate

  Catalysed by SLC16A4, SLC16A5, SLC16A6, SLC16A7 and 3 moreextracellular space, cytosol

• CMP-N-acetyl-beta-neuraminateReach from here →
  1. transport of acetoacetate and pyruvate (cytosol to mitochondria)
  2. N-Acetylneuraminate pyruvate-lyase (N-acetyl-D-mannosamine-forming)
  3. CTP:N-acetylneuraminate cytidylyltransferase

  Catalysed by NPL, CMASmitochondrial matrix, cytosol, nucleusOne of 2 routes

• spermidineReach from here →
  1. Acetoacetate:CoA ligase (AMP-forming)
  2. 3-hydroxy-3-methylglutaryl-CoA synthase (acetoacetyl-CoA)
  3. diamine N-acetyltransferase (N1-acetylspermidine)

  Catalysed by AACS, HMGCS1, SAT1, SAT2cytosolOne of 5 routes

• a 2-acyl-sn-glycero-3-phosphocholineReach from here →
  1. transport of acetate and acetoacetate (cytosol to extracellular)
  2. N-(acetyl)-sphing-4-enine + H2O = sphing-4-enine + acetate
  3. N-(acetyl)-sphing-4-enine + a 1,2-diacyl-sn-glycero-3-phosphocholine = 1-O-acyl-N-(acetyl)-sphing-4-enine + a 2-acyl-sn-glycero-3-phosphocholine

  Catalysed by SLC16A4, SLC16A5, SLC16A6, SLC16A7 and 3 moreextracellular space, cytosol

• L-tryptophanReach from here →
  1. transport of acetoacetate and pyruvate (cytosol to mitochondria)
  2. (R)-3-Amino-2-methylpropanoate:pyruvate aminotransferase
  3. transport of alanine and tryptophan (cytosol to extracellular)

  Catalysed by AGXT2, SLC7A5mitochondrial matrix, cytosol, extracellular spaceOne of 10 routes

• glutathioneReach from here →
  1. transport of acetoacetate and L-lactate (cytosol to extracellular)
  2. transport of L-lactate and urate (cytosol to extracellular)
  3. urate(out) + glutathione(in) = urate(in) + glutathione(out)

  Catalysed by SLC16A4, SLC16A5, SLC16A7, SLC16A8 and 3 moreextracellular space, cytosol, inner side of the membrane, outer side of the membrane

• L-threonineReach from here →
  1. transport of acetoacetate and pyruvate (cytosol to mitochondria)
  2. (R)-3-Amino-2-methylpropanoate:pyruvate aminotransferase
  3. L-threonine(out) + L-alanine(in) = L-threonine(in) + L-alanine(out)

  Catalysed by AGXT2, SLC7A10mitochondrial matrix, cytosol, inner side of the membrane, outer side of the membraneOne of 5 routes

• L-kynurenineReach from here →
  1. transport of acetoacetate and pyruvate (cytosol to mitochondria)
  2. (R)-3-Amino-2-methylpropanoate:pyruvate aminotransferase
  3. L-kynurenine + H2O = anthranilate + L-alanine + H(+)

  Catalysed by AGXT2, KYNUmitochondrial matrix, cytosol

• beta-alanineReach from here →
  1. transport of acetoacetate and pyruvate (cytosol to mitochondria)
  2. (R)-3-Amino-2-methylpropanoate:pyruvate aminotransferase
  3. beta-alanine(out) + L-alanine(in) = beta-alanine(in) + L-alanine(out)

  Catalysed by AGXT2, SLC7A10mitochondrial matrix, cytosol, inner side of the membrane, outer side of the membraneOne of 4 routes

• 2-hydroxy-3-oxopropanoateReach from here →
  1. transport of acetoacetate and pyruvate (cytosol to mitochondria)
  2. L-Serine:pyruvate aminotransferase
  3. hydroxypyruvate aldose-ketose-isomerase

  Catalysed by AGXT, HYImitochondrial matrix, cytosolOne of 2 routes

• L-asparagineReach from here →
  1. Acetoacetate:CoA ligase (AMP-forming)
  2. 3-hydroxy-3-methylglutaryl-CoA synthase (acetoacetyl-CoA)
  3. N-acetylglutamate synthase (N-acetyl-L-asparagine)

  Catalysed by AACS, HMGCS1, NAGScytosol, mitochondrial matrixOne of 12 routes

• L-phenylalanineReach from here →
  1. transport of acetoacetate and pyruvate (cytosol to mitochondria)
  2. (R)-3-Amino-2-methylpropanoate:pyruvate aminotransferase
  3. transport of alanine and phenylalanine (cytosol to extracellular)

  Catalysed by AGXT2, SLC7A5mitochondrial matrix, cytosol, extracellular spaceOne of 14 routes

• 3-hydroxy-L-kynurenineReach from here →
  1. transport of acetoacetate and pyruvate (cytosol to mitochondria)
  2. (R)-3-Amino-2-methylpropanoate:pyruvate aminotransferase
  3. 3-hydroxy-L-kynurenine + H2O = 3-hydroxyanthranilate + L-alanine + H(+)

  Catalysed by AGXT2, KYNUmitochondrial matrix, cytosol

• L,L-cystathionineReach from here →
  1. Acetoacetate:CoA ligase (AMP-forming)
  2. 3-hydroxy-3-methylglutaryl-CoA synthase (acetoacetyl-CoA)
  3. N-acetylglutamate synthase (N-acetyl-L-cystathionine)

  Catalysed by AACS, HMGCS1, NAGScytosol, mitochondrial matrix

• a 1-acyl-sn-glycero-3-phosphocholineReach from here →
  1. transport of acetate and acetoacetate (cytosol to extracellular)
  2. N-(acetyl)-sphing-4-enine + H2O = sphing-4-enine + acetate
  3. N-(acetyl)-sphing-4-enine + a 1,2-diacyl-sn-glycero-3-phosphocholine = 1-O-acyl-N-(acetyl)-sphing-4-enine + a 1-acyl-sn-glycero-3-phosphocholine

  Catalysed by SLC16A4, SLC16A5, SLC16A6, SLC16A7 and 3 moreextracellular space, cytosol

• L-homocysteineReach from here →
  1. transport of acetoacetate and pyruvate (cytosol to mitochondria)
  2. N(1)-methylguanosine(37) in tRNA(Phe) + pyruvate + S-adenosyl-L-methionine = 4-demethylwyosine(37) in tRNA(Phe) + 5'-deoxyadenosine + L-methionine + CO2 + H2O
  3. S-methyl-L-methionine + L-homocysteine = 2 L-methionine + H(+)

  Catalysed by TYW1B, TYW1, BHMT2mitochondrial matrix, cytosol

• S-methyl-L-methionineReach from here →
  1. transport of acetoacetate and pyruvate (cytosol to mitochondria)
  2. N(1)-methylguanosine(37) in tRNA(Phe) + pyruvate + S-adenosyl-L-methionine = 4-demethylwyosine(37) in tRNA(Phe) + 5'-deoxyadenosine + L-methionine + CO2 + H2O
  3. S-methyl-L-methionine + L-homocysteine = 2 L-methionine + H(+)

  Catalysed by TYW1B, TYW1, BHMT2mitochondrial matrix, cytosol

• (2R)-2-phosphoglycerateReach from here →
  1. transport of acetoacetate and pyruvate (cytosol to mitochondria)
  2. pyruvate kinase (dTDP)
  3. 2-phospho-D-glycerate hydro-lyase (phosphoenolpyruvate-forming)

  Catalysed by PKM, PKLR, ENO1, ENO2 and 1 moremitochondrial matrix, cytosol

• N(omega),N(omega)-dimethyl-L-arginineReach from here →
  1. transport of acetoacetate and pyruvate (cytosol to mitochondria)
  2. (R)-3-Amino-2-methylpropanoate:pyruvate aminotransferase
  3. N(omega),N(omega)-dimethyl-L-arginine + pyruvate = 5-(3,3-dimethylguanidino)-2-oxopentanoate + L-alanine

  Catalysed by AGXT2mitochondrial matrix, cytosolOne of 7 routes

• an acyl-CoAReach from here →
  1. Acetoacetate:CoA ligase (AMP-forming)
  2. 3-hydroxy-3-methylglutaryl-CoA synthase (acetoacetyl-CoA)
  3. acyl-CoA:sphingosine N-acyltransferase

  Catalysed by AACS, HMGCS1, ASAH1, ACER2 and 2 morecytosol, Golgi apparatusOne of 2 routes

• trans-4-hydroxy-L-prolineReach from here →
  1. transport of acetoacetate and pyruvate (cytosol to mitochondria)
  2. (R)-3-Amino-2-methylpropanoate:pyruvate aminotransferase
  3. trans-4-hydroxy-L-proline(out) + L-alanine(in) + Na(+)(out) = trans-4-hydroxy-L-proline(in) + L-alanine(out) + Na(+)(in)

  Catalysed by AGXT2, SLC1A4mitochondrial matrix, cytosol, inner side of the membrane, outer side of the membraneOne of 2 routes

• cadaverineReach from here →
  1. transport of acetate and acetoacetate (cytosol to extracellular)
  2. N-acetylcadaverine + H2O = cadaverine + acetate
  3. N-acetylcadaverine + H2O = cadaverine + acetate

  Catalysed by SLC16A4, SLC16A5, SLC16A6, SLC16A7 and 2 moreextracellular space, cytosol

• (2S)-2-[5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamido]succinateReach from here →
  1. 4-fumarylacetoacetate + H2O = acetoacetate + fumarate + H(+)
  2. 4-fumarylacetoacetate fumarylhydrolase
  3. 1-(5'-Phosphoribosyl)-5-amino-4-(N-succinocarboxamide)-imidazole AMP-lyase

  Catalysed by FAH, ADSLcytosolOne of 2 routes

• kynurenateReach from here →
  1. transport of acetoacetate and pyruvate (cytosol to mitochondria)
  2. 2-oxo-3-sulfanylpropanoate + [thioredoxin]-dithiol = [thioredoxin]-disulfide + hydrogen sulfide + pyruvate + H(+)
  3. 2-oxo-3-sulfanylpropanoate + L-kynurenine = kynurenate + L-cysteine + H2O

  Catalysed by MPST, AADATmitochondrial matrix, cytosolOne of 2 routes