N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine

Three steps

• oxaloacetateReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. (5Z,8Z,11Z,14Z)-eicosatetraenoate + AH2 + 2 O2 = prostaglandin H2 + A + H2O
  3. (R)-malate + A = oxaloacetate + AH2

  Catalysed by FAAH, FAAH2, PTGS1, PTGS2 and 1 more

• (S)-lactateReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. prostaglandin-endoperoxide synthase (arachidonate)
  3. prostaglandin H2(out) + 2 (S)-lactate(in) = prostaglandin H2(in) + 2 (S)-lactate(out)

  Catalysed by FAAH, FAAH2, PTGS1, PTGS2 and 1 morecytosol, inner side of the membrane, outer side of the membraneOne of 2 routes

• formaldehydeReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. (5Z,8Z,11Z,14Z)-eicosatetraenoate + AH2 + 2 O2 = prostaglandin H2 + A + H2O
  3. N(6),N(6)-dimethyl-L-lysyl(4)-[histone H3] + 2 A + 2 H2O = L-lysyl(4)-[histone H3] + 2 formaldehyde + 2 AH2

  Catalysed by FAAH, FAAH2, PTGS1, PTGS2 and 2 moreOne of 3 routes

• bilirubin IXalphaReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. transport of arachidonate (cytosol to extracellular)
  3. transport of bilirubin (cytosol to extracellular)

  Catalysed by FAAH, FAAH2, SLCO1B1, SLCO1A2 and 1 moreextracellular space, cytosolOne of 4 routes

• taurolithocholateReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. transport of arachidonate (cytosol to extracellular)
  3. transport of S-glutathionyl-2-4-dinitrobenzene (cytosol to extracellular)

  Catalysed by FAAH, FAAH2, SLCO1B1, SLCO1A2 and 1 moreextracellular space, cytosolOne of 4 routes

• CHEBI:17208Reach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. transport of arachidonate and GSH (cytosol to extracellular)
  3. glutathione:dehydroascorbate oxidoreductase

  Catalysed by FAAH, FAAH2extracellular space, cytosol

• homocysteineReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. transport of arachidonate and GSH (cytosol to extracellular)
  3. Formation of Homocystine

  Catalysed by FAAH, FAAH2extracellular space, cytosol

• all-trans-retinolReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. (5Z,8Z,11Z,14Z)-eicosatetraenoate + AH2 + 2 O2 = prostaglandin H2 + A + H2O
  3. all-trans-13,14-dihydroretinol + A = all-trans-retinol + AH2

  Catalysed by FAAH, FAAH2, PTGS1, PTGS2 and 1 more

• linoleic acidReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. (10Z)-heptadecenoic acid formation
  3. (10Z)-heptadecenoic acid formation

  Catalysed by FAAH, FAAH2cytosol, extracellular spaceOne of 14 routes

• O-hexadecanoyl-(R)-carnitineReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. Utilized Transport
  3. palmitoyl-CoA:L-carnitine O-palmitoyltransferase

  Catalysed by FAAH, FAAH2, CPT2, CPT1Aendoplasmic reticulum, cytosol, peroxisomeOne of 10 routes

• AH2Reach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. (5Z,8Z,11Z,14Z)-eicosatetraenoate + AH2 + 2 O2 = prostaglandin H2 + A + H2O
  3. A + NADH + H(+) = AH2 + NAD(+)

  Catalysed by FAAH, FAAH2, PTGS1, PTGS2 and 2 moreOne of 19 routes

• L-cysteineReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. transport of arachidonate and GSH (cytosol to extracellular)
  3. cystine to cysteine conversion

  Catalysed by FAAH, FAAH2extracellular space, cytosolOne of 2 routes

• glycerolReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. fatty acid amide hydrolase (2-arachidonoylglycerol)
  3. 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O = glycerol + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+)

  Catalysed by FAAH, FAAH2, CES2, ABHD16A and 8 morecytosol

• O-octanoyl-(R)-carnitineReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. Utilized Transport
  3. solute carrier (L-carnitine)

  Catalysed by FAAH, FAAH2, SLC25A20endoplasmic reticulum, cytosol, mitochondrial matrixOne of 7 routes

• dodecanoateReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. (10Z)-heptadecenoic acid formation
  3. (10Z)-heptadecenoic acid formation

  Catalysed by FAAH, FAAH2cytosol, extracellular spaceOne of 12 routes

• 20-O-(beta-D-glucuronosyl)-(5Z,8Z,11Z,14Z)-eicosatetraenoateReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. arachidonic acid:oxygen 1-oxidoreductase
  3. 20-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + UDP-alpha-D-glucuronate = 20-O-(beta-D-glucuronosyl)-(5Z,8Z,11Z,14Z)-eicosatetraenoate + UDP + H(+)

  Catalysed by FAAH, FAAH2, CYP1A1, CYP1A2 and 28 morecytosol

• (2E,5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoAReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. (5Z,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA = (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate
  3. (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + O2 = (2E,5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + H2O2

  Catalysed by FAAH, FAAH2, SLC27A2, ACSL4 and 10 more

• docosanoateReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. (10Z)-heptadecenoic acid formation
  3. (10Z)-heptadecenoic acid formation

  Catalysed by FAAH, FAAH2cytosol, extracellular spaceOne of 12 routes

• octadecanoateReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. (10Z)-heptadecenoic acid formation
  3. (10Z)-heptadecenoic acid formation

  Catalysed by FAAH, FAAH2cytosol, extracellular spaceOne of 12 routes

• alpha-linolenic acidReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. (10Z)-heptadecenoic acid formation
  3. (10Z)-heptadecenoic acid formation

  Catalysed by FAAH, FAAH2cytosol, extracellular spaceOne of 13 routes

• elaidic acidReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. (10Z)-heptadecenoic acid formation
  3. (10Z)-heptadecenoic acid formation

  Catalysed by FAAH, FAAH2cytosol, extracellular spaceOne of 12 routes

• all-cis-docosa-4,7,10,13,16,19-hexaenoic acidReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. (10Z)-heptadecenoic acid formation
  3. (10Z)-heptadecenoic acid formation

  Catalysed by FAAH, FAAH2cytosol, extracellular spaceOne of 12 routes

• 5(S)-HETEReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. Arachidonate:oxygen 5-oxidoreductase
  3. Glutathione: 5-HPETE oxidoreductase

  Catalysed by FAAH, FAAH2, ALOX5, GPX5 and 8 morecytosolOne of 4 routes

• CHEBI:28666Reach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. transport of arachidonate (cytosol to extracellular)
  3. transport of LTD4 (cytosol to extracellular)

  Catalysed by FAAH, FAAH2, SLCO1B1extracellular space, cytosolOne of 4 routes

• chlorine(.)Reach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. Utilized Transport
  3. Carnitine Transport by Atb0

  Catalysed by FAAH, FAAH2, SLC6A14endoplasmic reticulum, cytosol, extracellular space

• glycocholateReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. transport of arachidonate (cytosol to extracellular)
  3. solute carrier organic anion transporter (glycocholate)

  Catalysed by FAAH, FAAH2, SLCO1B1, SLCO1A2 and 1 moreextracellular space, cytosolOne of 4 routes

• cholateReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. transport of arachidonate (cytosol to extracellular)
  3. solute carrier organic anion transporter (cholate)

  Catalysed by FAAH, FAAH2, SLCO1B1, SLCO1A2 and 1 moreextracellular space, cytosolOne of 4 routes

• acetateReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. ethanolamine ammonia-lyase (acetaldehyde-forming)
  3. Acetaldehyde:NAD+ oxidoreductase

  Catalysed by FAAH, FAAH2, ALDH3A1, ALDH3B1 and 2 morecytosolOne of 4 routes

• tetradecanoateReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. (10Z)-heptadecenoic acid formation
  3. (10Z)-heptadecenoic acid formation

  Catalysed by FAAH, FAAH2cytosol, extracellular spaceOne of 12 routes

• (9Z)-octadecenoateReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. (10Z)-heptadecenoic acid formation
  3. (10Z)-heptadecenoic acid formation

  Catalysed by FAAH, FAAH2cytosol, extracellular spaceOne of 14 routes

• hexacosanoateReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. (10Z)-heptadecenoic acid formation
  3. (10Z)-heptadecenoic acid formation

  Catalysed by FAAH, FAAH2cytosol, extracellular spaceOne of 12 routes

• tetracosanoateReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. (10Z)-heptadecenoic acid formation
  3. (10Z)-heptadecenoic acid formation

  Catalysed by FAAH, FAAH2cytosol, extracellular spaceOne of 12 routes

• an N-acylsphinganineReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. (10Z)-heptadecenoic acid formation
  3. N-acylsphingosine amidohydrolase

  Catalysed by FAAH, FAAH2, ASAH1, ACER2 and 3 morecytosol

• eicosanoateReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. (10Z)-heptadecenoic acid formation
  3. (10Z)-heptadecenoic acid formation

  Catalysed by FAAH, FAAH2cytosol, extracellular spaceOne of 12 routes

• (9Z)-hexadecenoateReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. (10Z)-heptadecenoic acid formation
  3. (10Z)-heptadecenoic acid formation

  Catalysed by FAAH, FAAH2cytosol, extracellular spaceOne of 18 routes

• (15Z)-tetracosenoateReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. (10Z)-heptadecenoic acid formation
  3. (10Z)-heptadecenoic acid formation

  Catalysed by FAAH, FAAH2cytosol, extracellular spaceOne of 12 routes

• (11Z)-eicosenoateReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. (10Z)-heptadecenoic acid formation
  3. (10Z)-heptadecenoic acid formation

  Catalysed by FAAH, FAAH2cytosol, extracellular spaceOne of 12 routes

• serotoninReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. transport of arachidonate (cytosol to extracellular)
  3. transport of serotonin (cytosol to extracellular)

  Catalysed by FAAH, FAAH2, SLCO1B1, SLCO1A2 and 1 moreextracellular space, cytosolOne of 4 routes

• chenodeoxycholateReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. transport of arachidonate (cytosol to extracellular)
  3. solute carrier organic anion transporter (chenodiol)

  Catalysed by FAAH, FAAH2, SLCO1B1, SLCO1A2 and 1 moreextracellular space, cytosolOne of 2 routes

• taurocholateReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. transport of arachidonate (cytosol to extracellular)
  3. solute carrier organic anion transporter (S-glutathionyl-2-4-dinitrobenzene)

  Catalysed by FAAH, FAAH2, SLCO1B1, SLCO1A2 and 1 moreextracellular space, cytosolOne of 4 routes

• glycolithocholic acidReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. transport of arachidonate (cytosol to extracellular)
  3. transport of glycolithocholate (cytosol to extracellular)

  Catalysed by FAAH, FAAH2, SLCO1B1, SLCO1A2 and 1 moreextracellular space, cytosolOne of 4 routes

• gamma-Glu-AlaReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. transport of arachidonate and GSH (cytosol to extracellular)
  3. gamma-glutamyltransferase (alanine)

  Catalysed by FAAH, FAAH2, GGT1, GGT5 and 4 moreextracellular space, cytosol

• 3,3',5-triiodo-L-thyronineReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. transport of arachidonate (cytosol to extracellular)
  3. transport of S-glutathionyl-2-4-dinitrobenzene (cytosol to extracellular)

  Catalysed by FAAH, FAAH2, SLCO1B1, SLCO1A2 and 1 moreextracellular space, cytosolOne of 4 routes

• 1-O-hexadecyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholineReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. (5Z,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA = (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate
  3. 1-O-hexadecyl-sn-glycero-3-phosphocholine + (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA = 1-O-hexadecyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine + CoA

  Catalysed by FAAH, FAAH2, SLC27A2, ACSL4 and 10 more

• malonaldehydeReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. prostaglandin-endoperoxide synthase (arachidonate)
  3. thromboxane A synthase (12(S)-HHT)

  Catalysed by FAAH, FAAH2, PTGS1, PTGS2 and 1 morecytosolOne of 2 routes

• glycineReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-glycine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + glycine
  3. N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-glycine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + glycine

  Catalysed by FAAH, FAAH2, PM20D1

• butanoyl-CoAReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. Utilized Transport
  3. transport of butyryl-CoA and L-carnitine (cytosol to mitochondria)

  Catalysed by FAAH, FAAH2, SLC33A1, ESCO2 and 1 moreendoplasmic reticulum, cytosol, mitochondrial matrixOne of 2 routes

• prostaglandin E1Reach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. transport of arachidonate (cytosol to extracellular)
  3. transport of prostaglandin E1 (cytosol to extracellular)

  Catalysed by FAAH, FAAH2, SLCO1B1extracellular space, cytosolOne of 4 routes

• prostaglandin I2Reach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. transport of arachidonate (cytosol to extracellular)
  3. transport of prostaglandin I2 (cytosol to extracellular)

  Catalysed by FAAH, FAAH2, SLCO1B1extracellular space, cytosolOne of 6 routes

• prostaglandin F2alphaReach from here →
  1. N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + H2O = ethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate
  2. transport of arachidonate (cytosol to extracellular)
  3. transport of prostaglandin F2alpha (cytosol to extracellular)

  Catalysed by FAAH, FAAH2, SLCO1B1extracellular space, cytosolOne of 6 routes