Eukaryotic cytosolic de novo fatty acid synthesis (type I FAS)

Cytosolic de novo fatty acid synthesis builds long-chain saturated fatty acids (mainly C16:0 and C18:0) from acetyl-CoA in eukaryotes, supplying membrane phospholipids, sphingolipids, storage triacylglycerol and acylated proteins. Cytosolic acetyl-CoA is supplied either by ATP-citrate lyase, which cleaves citrate exported from mitochondria (animals, plants and many fungi such as fission yeast), or, in yeasts without ATP-citrate lyase, by acetyl-CoA synthetase acting on acetate. A biotin-dependent multidomain acetyl-CoA carboxylase then carboxylates acetyl-CoA to malonyl-CoA in the committed, highly regulated step. The chain is assembled by a type I fatty acid synthase (FAS), a multifunctional megasynthase that carries all the acyl-transfer, condensation, reduction, dehydration and acyl-carrier activities on large polypeptides and iteratively adds two-carbon units from malonyl-CoA using NADPH. Two unrelated architectures carry out this step: the animal FAS is a homodimer of a single polypeptide that releases free palmitate through a thioesterase, whereas the fungal FAS is a 2.6 MDa alpha6-beta6 barrel built from two polypeptides that releases the product as acyl-CoA (mostly palmitoyl- and stearoyl-CoA) through a malonyl/palmitoyl-transferase domain. In animals an auxiliary thioesterase can release medium-chain fatty acids early. Saturated acyl-CoAs are commonly desaturated by an endoplasmic-reticulum delta-9 stearoyl-CoA desaturase to palmitoleoyl- and oleoyl-CoA. Chain extension beyond C16-C18 is carried out by the separate microsomal elongation cycle, and the mitochondrial dissociated (type II) FAS that makes the octanoyl precursor of lipoic acid is a distinct pathway.

MODULE:fatty_acid_de_novo_synthesisDRAFTMetabolic Pathwaymodules/fatty_acid_de_novo_synthesis.yaml
fatty acid biosynthetic processGO:0006633 malonyl-CoA biosynthetic processGO:2001295
YeastPathways:PWY3O-5962
superpathway of fatty acid biosynthesis, saturated and unsaturated (S. cerevisiae, SGD YeastPathways)
YeastCyc superpathway combining ACC1/HFA1 carboxylation, FAS1/FAS2 chain assembly (with CEM1, OAR1 and MCT1 also listed as catalysts) and OLE1 desaturation. HFA1, CEM1, OAR1 and MCT1 are mitochondrial FAS II enzymes and are modelled in type_ii_fatty_acid_synthesis instead.
YeastPathways:PWY3O-6336
superpathway of fatty acid biosynthesis, saturated (S. cerevisiae, SGD YeastPathways)
Saturated superpathway; same catalyst list as PWY3O-5962 without OLE1.
YeastPathways:PWY3O-10
fatty acid biosynthesis, initial steps (S. cerevisiae, SGD YeastPathways)
Carboxylation, acetyl/malonyl loading and the first condensation and reduction round, assigned to ACC1, HFA1, FAS1, FAS2, MCT1 and CEM1.
YeastPathways:PWY-5971-1
myristate biosynthesis (S. cerevisiae, SGD YeastPathways)
Iterative FAS1/FAS2 rounds up to myristoyl-CoA; the 3-oxoacyl reductions are given no gene although FAS2 carries the ketoreductase domain.
YeastPathways:PWY3O-8514
palmitate biosynthesis (S. cerevisiae, SGD YeastPathways)
FAS1/FAS2 round from myristoyl- to palmitoyl-ACP and release as palmitoyl-CoA.
YeastPathways:PWY3O-355
stearate biosynthesis III (fungi) (S. cerevisiae, SGD YeastPathways)
FAS1/FAS2 round from palmitoyl- to stearoyl-ACP; CEM1 is also listed as condensing enzyme, which is not supported.
YeastPathways:PWY3O-31723
fatty acids biosynthesis (yeast) (S. cerevisiae, SGD YeastPathways)
Single lumped FATTY-ACYL-COA-SYNTHASE-RXN (EC 2.3.1.86) catalysed by FAS1 and FAS2, producing long-chain acyl-CoA.
YeastPathways:PWY3O-5268
oleate biosynthesis (S. cerevisiae, SGD YeastPathways)
OLE1 delta-9 desaturation of stearoyl-CoA; the subsequent thioester hydrolysis to free oleate has no assigned gene.
YeastPathways:PWY3O-1801
palmitoleate biosynthesis (S. cerevisiae, SGD YeastPathways)
OLE1 delta-9 desaturation of palmitoyl-CoA; hydrolysis to free palmitoleate has no assigned gene.
GO:0006633
fatty acid biosynthetic process
Module-level process for the carboxylation and chain-assembly core.
GO:2001295
malonyl-CoA biosynthetic process
Acetyl-CoA carboxylase produces malonyl-CoA, the two-carbon donor.
GO:0006636
unsaturated fatty acid biosynthetic process
Process of the optional delta-9 desaturation part.
PMID:17448991
The crystal structure of yeast fatty acid synthase, a cellular machine with eight active sites working together.
In yeast the entire pathway to 16- and 18-carbon fatty acids is carried out by a 2.6 MDa FAS assembly containing six copies of all eight catalytic centres.
PMID:8098706
Acetyl-CoA carboxylase from yeast is an essential enzyme and is regulated by factors that control phospholipid metabolism.
ACC1 encodes the 250 kDa biotin-containing acetyl-CoA carboxylase; acc1 spores are inviable even with fatty acid supplementation.
PMID:1350093
Cloning of the yeast FAS3 gene and primary structure of yeast acetyl-CoA carboxylase.
FAS3 (= ACC1) encodes acetyl-CoA carboxylase, conserved with chicken and rat carboxylases.
PMID:14761959
HFA1 encoding an organelle-specific acetyl-CoA carboxylase controls mitochondrial fatty acid synthesis in Saccharomyces cerevisiae.
HFA1 and ACC1 do not complement each other; ACC1 serves cytoplasmic fatty acid synthesis whereas HFA1 is the mitochondrial carboxylase, so HFA1 is excluded from this cytosolic module.
PMID:1978720
The OLE1 gene of Saccharomyces cerevisiae encodes the delta 9 fatty acid desaturase and can be functionally replaced by the rat stearoyl-CoA desaturase gene.
OLE1 encodes the delta-9 desaturase required for unsaturated fatty acid synthesis and is replaceable by rat stearoyl-CoA desaturase.
PMID:16920014
Regulation of long chain unsaturated fatty acid synthesis in yeast.
Ole1p is an ER membrane desaturase with a fused C-terminal cytochrome b5 domain that receives electrons from NADH via cytochrome b5 reductase.
PMID:24520995
Yeast lipid metabolism at a glance.
Review of yeast fatty acid synthesis, elongation, desaturation and degradation used for boundary setting.
file:human/ACLY/ACLY-ai-review.yaml
ACLY gene review (human)
ATP-citrate lyase (UniProtKB:P53396, GO:0003878) matches the completed human ACLY review.
file:human/ACACA/ACACA-ai-review.yaml
ACACA gene review (human)
Acetyl-CoA carboxylase 1 (UniProtKB:Q13085, GO:0003989) matches the completed human ACACA review.
file:human/ACACB/ACACB-ai-review.yaml
ACACB gene review (human)
Acetyl-CoA carboxylase 2 (UniProtKB:O00763, GO:0003989) matches the completed human ACACB review.
file:human/FASN/FASN-ai-review.yaml
FASN gene review (human)
Fatty acid synthase (UniProtKB:P49327, GO:0004312) matches the completed human FASN review.
file:human/OLAH/OLAH-ai-review.yaml
OLAH gene review (human)
Oleoyl-ACP hydrolase / thioesterase II (UniProtKB:Q9NV23, GO:0016297) matches the completed human OLAH review.
10Nodes
5Parts
2Variant Sets
4Variants
7Annotons
4Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:fatty_acid_de_novo_synthesis deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Reaction chaining (advisory)

✓ every PRECEDES step chains, or its break is acknowledged via chaining_status.

  • acetyl_coa_generation → malonyl_coa_synthesis [VERIFIED]
    shared: acetylcoa
  • malonyl_coa_synthesis → palmitate_synthesis [VERIFIED]
    shared: acetylcoa
  • palmitate_synthesis → delta9_desaturation [VERIFIED]
    The fungal FAS product (GO:0004321) is palmitoyl-/stearoyl-CoA, the substrate of GO:0004768; for animal FASN the free palmitate must first be activated to acyl-CoA, a step outside this module.

Function consistency and core coverage

15 gene-function check(s) reflected in core functions · 0 conflict(s) · 3 evidence or coverage gap(s) (29 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
acly_activity ACLY (human)
UniProtKB:P53396
Family Representative 		ATP citrate synthase activity
GO:0003878 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
acly_activity acl1 (Schizosaccharomyces pombe)
UniProtKB:Q9P7W3
Family Representative 		ATP citrate synthase activity
GO:0003878 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
acs_activity ACS2 (Saccharomyces cerevisiae)
UniProtKB:P52910
Family Representative 		acetyl-CoA synthetase activity
GO:0003987 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
acc_activity ACACA / ACC1 (human; cytosolic lipogenic)
UniProtKB:Q13085
Family Representative 		acetyl-CoA carboxylase activity
GO:0003989 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
acc_activity ACACB / ACC2 (human; mito-OM, FAO-regulating)
UniProtKB:O00763
Family Representative 		acetyl-CoA carboxylase activity
GO:0003989 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
acc_activity ACC1 (Saccharomyces cerevisiae)
UniProtKB:Q00955
Family Representative 		acetyl-CoA carboxylase activity
GO:0003989 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
acc_activity cut6 (Schizosaccharomyces pombe)
UniProtKB:P78820
Family Representative 		acetyl-CoA carboxylase activity
GO:0003989 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fasn_activity FASN (human)
UniProtKB:P49327
Family Representative 		fatty acid synthase activity
GO:0004312 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fungal_fas_activity PROTEIN_COMPLEX
Gene 		fatty-acyl-CoA synthase activity
GO:0004321 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
fungal_fas_activity/fas2_alpha_unit FAS2 (Saccharomyces cerevisiae)
UniProtKB:P19097
Family Representative 		3-oxoacyl-[acyl-carrier-protein] synthase activity
GO:0004315 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fungal_fas_activity/fas2_alpha_unit fas2 (Schizosaccharomyces pombe)
UniProtKB:Q10289
Family Representative 		3-oxoacyl-[acyl-carrier-protein] synthase activity
GO:0004315 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fungal_fas_activity/fas1_beta_unit FAS1 (Saccharomyces cerevisiae)
UniProtKB:P07149
Family Representative 		[acyl-carrier-protein] S-malonyltransferase activity
GO:0004314 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fungal_fas_activity/fas1_beta_unit fas1 (Schizosaccharomyces pombe)
UniProtKB:Q9UUG0
Family Representative 		[acyl-carrier-protein] S-malonyltransferase activity
GO:0004314 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
olah_activity OLAH (human)
UniProtKB:Q9NV23
Family Representative 		fatty acyl-[ACP] hydrolase activity
GO:0016297 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
scd_activity SCD (human)
UniProtKB:O00767
Family Representative 		stearoyl-CoA 9-desaturase activity
GO:0004768 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
scd_activity OLE1 (Saccharomyces cerevisiae)
UniProtKB:P21147
Family Representative 		stearoyl-CoA 9-desaturase activity
GO:0004768 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
scd_activity ole1 (Schizosaccharomyces pombe)
UniProtKB:O94523
Family Representative 		stearoyl-CoA 9-desaturase activity
GO:0004768 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
acly_activity ACLY / ATP-citrate lyase family
PANTHER:PTHR23118
Family 		ATP citrate synthase activity
GO:0003878 		Family Supported
Family review supports GO:0003878 FAMILY_WIDE. Asserted by fatty_acid_de_novo_synthesis; accepted by acl1 and ACLY.
acs_activity acetyl-CoA synthetase family
PANTHER:PTHR24095
Family 		acetyl-CoA synthetase activity
GO:0003987 		Family Supported
Family review supports GO:0003987 FAMILY_WIDE. Asserted by pdh_bypass_acetyl_coa_synthesis and fatty_acid_de_novo_synthesis; accepted by ACS1, ACS2 and both P. putida AcsA paralogs.
acc_activity ACC / eukaryotic multidomain acetyl-CoA carboxylase family
PANTHER:PTHR45728
Family 		acetyl-CoA carboxylase activity
GO:0003989 		Family Supported
Family review supports GO:0003989 FAMILY_WIDE. Asserted by fatty_acid_de_novo_synthesis and type_ii_fatty_acid_synthesis; accepted by every reviewed member.
fasn_activity FASN / animal fatty acid synthase (type I) family
PANTHER:PTHR43775:SF7
Family 		fatty acid synthase activity
GO:0004312 		Family Supported
Family review supports GO:0004312 for PANTHER:PTHR43775:SF7. Asserted by fatty_acid_de_novo_synthesis for FASN (SF7).
fas2_alpha_unit fungal FAS alpha subunit
Family 		3-oxoacyl-[acyl-carrier-protein] synthase activity
GO:0004315 		Family Id Missing
The family has no identifier linking it to a curated family review.
fas1_beta_unit fungal FAS beta subunit
Family 		[acyl-carrier-protein] S-malonyltransferase activity
GO:0004314 		Family Id Missing
The family has no identifier linking it to a curated family review.
olah_activity OLAH / S-acyl fatty acid synthase thioesterase family
PANTHER:PTHR11487
Family 		fatty acyl-[ACP] hydrolase activity
GO:0016297 		Family Supported
Family review supports GO:0016297 FAMILY_WIDE. Asserted by fatty_acid_de_novo_synthesis for OLAH; the bacterial members hydrolyse acyl thioesters on carrier domains.
scd_activity acyl-CoA delta-9 desaturase family
PANTHER:PTHR11351:SF31
Family 		stearoyl-CoA 9-desaturase activity
GO:0004768 		Family Supported
Family review supports GO:0004768 for PANTHER:PTHR11351:SF31. Fungal and animal delta-9 desaturase subfamilies. fatty_acid_de_novo_synthesis selects the base family, which also takes in desaturases of other regiospecificity.
scd_activity acyl-CoA delta-9 desaturase family
PANTHER:PTHR11351:SF102
Family 		stearoyl-CoA 9-desaturase activity
GO:0004768 		Family Supported
Family review supports GO:0004768 for PANTHER:PTHR11351:SF102. Fungal and animal delta-9 desaturase subfamilies. fatty_acid_de_novo_synthesis selects the base family, which also takes in desaturases of other regiospecificity.
scd_activity acyl-CoA delta-9 desaturase family
PANTHER:PTHR11351:SF97
Family 		stearoyl-CoA 9-desaturase activity
GO:0004768 		Family Supported
Family review supports GO:0004768 for PANTHER:PTHR11351:SF97. Fungal and animal delta-9 desaturase subfamilies. fatty_acid_de_novo_synthesis selects the base family, which also takes in desaturases of other regiospecificity.
scd_activity acyl-CoA delta-9 desaturase family
PANTHER:PTHR11351:SF100
Family 		stearoyl-CoA 9-desaturase activity
GO:0004768 		Family Supported
Family review supports GO:0004768 for PANTHER:PTHR11351:SF100. Fungal and animal delta-9 desaturase subfamilies. fatty_acid_de_novo_synthesis selects the base family, which also takes in desaturases of other regiospecificity.
scd_activity acyl-CoA delta-9 desaturase family
PANTHER:PTHR11351:SF39
Family 		stearoyl-CoA 9-desaturase activity
GO:0004768 		Family Supported
Family review supports GO:0004768 for PANTHER:PTHR11351:SF39. Fungal and animal delta-9 desaturase subfamilies. fatty_acid_de_novo_synthesis selects the base family, which also takes in desaturases of other regiospecificity.

Gene-review completeness (15/16 grounded genes reviewed)

12 complete review(s) · 5 with deep research · 1 missing review · 10 reviewed but lacking deep research

Gene Review Complete Deep research
ACACA Q13085 ✓ ✓ ✗
ACACB O00763 ✓ ✓ ✗
ACC1 Q00955 ✓ ✓ ✓
acl1 Q9P7W3 ✓ ✓ ✗
ACLY P53396 ✓ ✓ ✗
ACS2 P52910 ✓ 26/27 ✓
cut6 P78820 ✓ 15/16 ✗
FAS1 P07149 ✓ 83/84 ✓
fas1 Q9UUG0 ✓ ✓ ✗
FAS2 P19097 ✓ ✓ ✓
fas2 Q10289 ✓ ✓ ✗
FASN P49327 ✓ ✓ ✗
SCD (human) O00767 ✗ — —
OLAH Q9NV23 ✓ ✓ ✗
ole1 O94523 ✓ ✓ ✗
OLE1 P21147 ✓ ✓ ✓

Details

Context
EukaryotaNCBITaxon:2759
cytosolGO:0005829
Eukaryotic cytosolic de novo fatty acid synthesisMetabolic Pathwayfatty_acid_de_novo_synthesis
fatty acid biosynthetic processGO:0006633 malonyl-CoA biosynthetic processGO:2001295
Context
EukaryotaNCBITaxon:2759
cytosolGO:0005829

GENERALIZE (YeastPathways project, 2026-10): the former human-only lipogenesis module (ACLY -> ACACA/ACACB -> FASN -> OLAH) was broadened to eukaryotic cytosolic type I FAS. Nine YeastCyc frames (PWY3O-5962, PWY3O-6336, PWY3O-10, PWY-5971-1, PWY3O-8514, PWY3O-355, PWY3O-31723, PWY3O-5268, PWY3O-1801) are partitions of one pathway and map onto parts 2, 3 and 5. Changes: (1) acetyl-CoA supply became a ONE_OR_MORE variant set with ATP-citrate lyase (human ACLY, S. pombe acl1) and the acetate / acetyl-CoA synthetase route used by S. cerevisiae, which lacks ATP-citrate lyase (ACS2 representative; pdh_bypass_acetyl_coa_synthesis is authoritative for that route). S. pombe ATP-citrate lyase is heteromeric (acl1 + acl2); acl2 is in a different PANTHER family and is mentioned only in the acl1 description. (2) ACC gained S. cerevisiae ACC1 and S. pombe cut6 (both PTHR45728). (3) chain assembly became an EXACTLY_ONE variant set: animal homodimeric FASN (GO:0004312, free palmitate) vs the fungal alpha6-beta6 FAS complex (GO:0005835; FAS1 beta + FAS2 alpha; GO:0004321 fatty-acyl-CoA synthase activity because the product leaves as acyl-CoA). The fungal subunits carry no PANTHER term: UniProt and PANTHER place both FAS1 and FAS2 in PTHR10982:SF21 "FATTY ACID SYNTHASE SUBUNIT BETA" under the malonyl-CoA ACP transacylase family, which does not describe the alpha subunit; family membership was not used as a role descriptor. (4) OLAH became optional (animal-specific). (5) a new optional delta-9 desaturation part (SCD/OLE1/ole1, PTHR11351, GO:0004768, ER membrane) was added. The module context is now Eukaryota + cytosol; the desaturase location is given on its annoton. ACACB's mitochondrial outer membrane location and its regulatory role in beta-oxidation remain in its gene review rather than in module context. YeastCyc corrections: HFA1 is the mitochondrial acetyl-CoA carboxylase (PMID:14761959), and CEM1, OAR1 and MCT1 are mitochondrial FAS II enzymes; YeastCyc lists them as catalysts of the cytosolic FAS reactions, and they are modelled in type_ii_fatty_acid_synthesis instead. YeastCyc gives no gene for many 3-oxoacyl-ACP reductions (FAS2 KR domain) and none for the final acyl-CoA hydrolysis steps. GO-CAM disagreements: the YeastPathways models place every activity, including ER-membrane OLE1, in cytosol, attach mitochondrial HFA1/CEM1/OAR1/MCT1 to cytosolic FAS reaction nodes, type two FAS1 partial reactions only as GO:0003674, type one FAS1 enoyl-reductase node as GO:0004318 (NADH) although the fungal enzyme uses NADPH, and attach TES1 (a peroxisomal thioesterase) to the cytosolic acyl-CoA hydrolysis reactions. The PomBase model 678073a900002931 agrees with the cytosolic core and additionally contains mitochondrial FAS II, the ER elongation cycle, citrate transport and lipoylation, which belong to other modules. Very-long-chain extension is in fatty_acid_elongation_cycle.

Connections

Cytosolic acetyl-CoA is carboxylated to malonyl-CoA (and also primes FAS).
Malonyl-CoA is the two-carbon donor for chain assembly.
OLAH hydrolyses the FASN-bound acyl-ACP to release medium-chain fatty acids early (animal FASN only).
Palmitoyl- and stearoyl-CoA (made directly by fungal FAS, or after activation of FASN-released palmitate and microsomal elongation in animals) are desaturated at delta-9.
Part 1: cytosolic acetyl-CoA supply
Cytosolic acetyl-CoA supplyMetabolic Pathwayacetyl_coa_generation

Cytosolic acetyl-CoA, the FAS primer and carboxylase substrate, is made from mitochondria-exported citrate by ATP-citrate lyase or, in lineages without ATP-citrate lyase, from acetate by acetyl-CoA synthetase.

Variant set: Source of cytosolic acetyl-CoA by enzyme route (lineage) (One Or More)
ATP-citrate lyase (animals, plants, many fungi)Reactionacly_route

Annotons

ACLY: ATP-citrate lyase
acly_activity
Participant: Family: ACLY / ATP-citrate lyase family
Family:
ACLY / ATP-citrate lyase familyPANTHER:PTHR23118
Representative Members: ACLY (human)UniProtKB:P53396 acl1 (Schizosaccharomyces pombe)UniProtKB:Q9P7W3

Function

ATP citrate synthase activityGO:0003878
Substrates: citrate ATP CoA
Products: acetyl-CoA oxaloacetate ADP + phosphate

Locations

cytosolGO:0005829

Regenerate cytosolic acetyl-CoA from mitochondria-exported citrate.

Acetate activation by acetyl-CoA synthetase (yeasts lacking ATP-citrate lyase)Reactionacetyl_coa_synthetase_route

Annotons

ACS: cytosolic acetyl-CoA synthetase
acs_activity
Participant: Family: acetyl-CoA synthetase family
Family:
acetyl-CoA synthetase familyPANTHER:PTHR24095
Representative Members: ACS2 (Saccharomyces cerevisiae)UniProtKB:P52910

Function

acetyl-CoA synthetase activityGO:0003987
Substrates: acetate ATP CoA
Products: acetyl-CoA AMP + diphosphate

Locations

cytosolGO:0005829

Activate acetate (from the pyruvate dehydrogenase bypass) to cytosolic acetyl-CoA; the full route is modelled in pdh_bypass_acetyl_coa_synthesis.

Part 2: acetyl-CoA carboxylation (committed step)
Cytosolic multidomain acetyl-CoA carboxylaseReactionmalonyl_coa_synthesis

Annotons

ACC: biotin-dependent multidomain acetyl-CoA carboxylase
acc_activity
Participant: Family: ACC / eukaryotic multidomain acetyl-CoA carboxylase family
Family:
ACC / eukaryotic multidomain acetyl-CoA carboxylase familyPANTHER:PTHR45728
Representative Members: ACACA / ACC1 (human; cytosolic lipogenic)UniProtKB:Q13085 ACACB / ACC2 (human; mito-OM, FAO-regulating)UniProtKB:O00763 ACC1 (Saccharomyces cerevisiae)UniProtKB:Q00955 cut6 (Schizosaccharomyces pombe)UniProtKB:P78820

Function

acetyl-CoA carboxylase activityGO:0003989
Substrates: acetyl-CoA hydrogencarbonate (HCO3-) ATP (biotin cofactor)
Products: malonyl-CoA ADP + phosphate

Locations

cytosolGO:0005829

Carboxylate acetyl-CoA to malonyl-CoA (committed, rate-limiting step).

Part 3: fatty acid chain assembly by a type I megasynthase
Type I fatty acid synthaseMetabolic Pathwaypalmitate_synthesis

One acetyl primer and seven (or eight) malonyl extender units are condensed, reduced, dehydrated and reduced again on a single multienzyme. The animal and fungal megasynthases are not homologous as assemblies and differ in domain order, quaternary structure and product release.

Variant set: Type I FAS architecture by enzyme architecture (lineage) (Exactly One)
Animal homodimeric FASN releasing free palmitateReactionanimal_fasn_variant

Annotons

FASN: fatty acid synthase (homodimeric megasynthase)
fasn_activity
Participant: Family: FASN / animal fatty acid synthase (type I) family
Family:
FASN / animal fatty acid synthase (type I) family
Representative Members: FASN (human)UniProtKB:P49327

Function

fatty acid synthase activityGO:0004312
Substrates: acetyl-CoA (primer) malonyl-CoA (7 units) NADPH
Products: palmitate (C16:0) CoA + CO2

Locations

cytosolGO:0005829

Assemble palmitate and release it as the free acid via the integral thioesterase.

Fungal alpha6-beta6 FAS releasing acyl-CoAProtein Complexfungal_fas_variant

Annotons

FAS1/FAS2: fungal alpha6-beta6 fatty acid synthase
fungal_fas_activity
Participant: Protein Complex: fungal type I fatty acid synthase complex (alpha6-beta6)
Protein Complex:
fungal type I fatty acid synthase complex (alpha6-beta6)GO:0005835 2.6 MDa barrel of six alpha (FAS2) and six beta (FAS1) subunits with six copies of all eight catalytic centres and the ACP domain shuttling inside the reaction chambers (PMID:17448991).
Active units:
FAS2 alpha subunit (ACP, ketoacyl reductase, ketoacyl synthase, phosphopantetheinyl transferase)
Participant: Family: fungal FAS alpha subunit
Family:
fungal FAS alpha subunit
Representative Members: FAS2 (Saccharomyces cerevisiae)UniProtKB:P19097 fas2 (Schizosaccharomyces pombe)UniProtKB:Q10289
Role: Carries the acyl carrier domain, the 3-oxoacyl synthase and 3-oxoacyl reductase active sites, and the phosphopantetheinyl transferase that activates the ACP domain.
Function:
3-oxoacyl-[acyl-carrier-protein] synthase activityGO:0004315
FAS1 beta subunit (acetyl- and malonyl/palmitoyl-transferase, dehydratase, enoyl reductase)
Participant: Family: fungal FAS beta subunit
Family:
fungal FAS beta subunit
Representative Members: FAS1 (Saccharomyces cerevisiae)UniProtKB:P07149 fas1 (Schizosaccharomyces pombe)UniProtKB:Q9UUG0
Role: Carries the acetyltransferase, malonyl/palmitoyl transferase, 3-hydroxyacyl dehydratase and enoyl reductase active sites; the malonyl/palmitoyl transferase transfers the finished acyl chain to CoA.
Function:
[acyl-carrier-protein] S-malonyltransferase activityGO:0004314

Function

fatty-acyl-CoA synthase activityGO:0004321
Substrates: acetyl-CoA (primer) malonyl-CoA (7-8 units) NADPH
Products: palmitoyl-CoA and stearoyl-CoA (minor myristoyl-CoA) CoA + CO2

Locations

cytosolGO:0005829

Assemble palmitoyl- and stearoyl-CoA and release them as CoA thioesters, without a free fatty acid intermediate.

Part 4: early medium-chain product release (animal mammary gland) (optional)
Oleoyl-ACP hydrolase / thioesterase II (OLAH)Reactionmedium_chain_release

Annotons

OLAH: fatty acyl-ACP hydrolase (thioesterase II)
olah_activity
Participant: Family: OLAH / S-acyl fatty acid synthase thioesterase family
Family:
OLAH / S-acyl fatty acid synthase thioesterase familyPANTHER:PTHR11487
Representative Members: OLAH (human)UniProtKB:Q9NV23

Function

fatty acyl-[ACP] hydrolase activityGO:0016297
Substrates: medium-chain acyl-[ACP] (on the FASN carrier) H2O
Products: medium-chain fatty acid (C8-C14) holo-[ACP]

Locations

cytosolGO:0005829

Release medium-chain fatty acids from the animal FASN acyl-carrier.

Part 5: delta-9 desaturation of saturated acyl-CoA (optional)
Stearoyl-CoA delta-9 desaturaseReactiondelta9_desaturation

Annotons

SCD/OLE1: ER delta-9 acyl-CoA desaturase
scd_activity
Participant: Family: acyl-CoA delta-9 desaturase family
Family:
acyl-CoA delta-9 desaturase family
Representative Members: SCD (human)UniProtKB:O00767 OLE1 (Saccharomyces cerevisiae)UniProtKB:P21147 ole1 (Schizosaccharomyces pombe)UniProtKB:O94523

Function

stearoyl-CoA 9-desaturase activityGO:0004768
Substrates: palmitoyl-CoA or stearoyl-CoA O2 reduced cytochrome b5
Products: palmitoleoyl-CoA or oleoyl-CoA H2O

Processes

unsaturated fatty acid biosynthetic processGO:0006636

Locations

endoplasmic reticulum membraneGO:0005789

Introduce a cis delta-9 double bond into palmitoyl- and stearoyl-CoA, giving the monounsaturated acyl-CoAs of membrane lipids.