Eukaryotic polyamine metabolism (biosynthesis, back-conversion and antizyme feedback)

The polyamines putrescine, spermidine and spermine are small polycations needed for eukaryotic cell growth. They stabilise nucleic acids and chromatin, regulate ion channels and act in translation. Spermidine is also the precursor of the hypusine modification of eIF5A, which is why it is essential in yeast. Biosynthesis begins with ornithine decarboxylase (ODC), a short-lived PLP-dependent enzyme that decarboxylates L-ornithine to putrescine and is the main control point. Some lineages also make putrescine by hydrolysing agmatine with agmatinase. In parallel, a pyruvoyl-dependent S-adenosylmethionine decarboxylase makes decarboxylated SAM (dcSAM), the only aminopropyl donor. Spermidine synthase transfers an aminopropyl group from dcSAM to putrescine to make spermidine. Where spermine is made, a spermine synthase adds a second aminopropyl group. Animals use a dedicated SMS family for this, and budding yeasts use the SPE3 paralogue SPE4. Each transfer releases 5'-methylthioadenosine (MTA), which the methionine salvage cycle recycles. Back-conversion catabolism oxidises spermine or N1-acetylated polyamines with FAD-dependent polyamine oxidases to give shorter polyamines plus an aminoaldehyde and H2O2. In animals, SAT1 N1-acetylates polyamines and peroxisomal PAOX then oxidises them, while SMOX oxidises free spermine. In budding yeast a single oxidase, Fms1, oxidises both spermine and N1-acetylpolyamines, and its 3-aminopropanal product is the source of beta-alanine for pantothenate and coenzyme A synthesis. ODC is controlled by antizyme, a protein whose synthesis needs a +1 ribosomal frameshift that polyamines stimulate. Antizyme binds ODC and targets it for ubiquitin-independent proteasomal degradation. In vertebrates, antizyme inhibitors (catalytically dead ODC paralogues) bind antizyme and release ODC.

MODULE:polyamine_metabolismDRAFTMetabolic Pathwaymodules/polyamine_metabolism.yaml

polyamine biosynthetic processGO:0006596 polyamine catabolic processGO:0006598

YeastPathways:POLYAMSYN-YEAST-PWY

superpathway of polyamine biosynthesis

Source superpathway for S. cerevisiae: SPE1 ODC, SPE2 AdoMetDC, SPE3 spermidine synthase and SPE4 spermine synthase. All four assignments are kept. YeastCyc has no catabolic or regulatory frame; FMS1, PAA1 and OAZ1 were added from the literature.

YeastPathways:BSUBPOLYAMSYN-PWY

spermidine biosynthesis I

SPE2 and SPE3 subpathway (dcSAM + putrescine to spermidine).

YeastPathways:ARGSPECAT-PWY

spermine biosynthesis

SPE2 and SPE4 subpathway (dcSAM + spermidine to spermine).

YeastPathways:PWY-46

putrescine biosynthesis III

SPE1 ornithine decarboxylase (ornithine to putrescine).

GO:0006596

polyamine biosynthetic process

ODC (or agmatinase), AdoMetDC, spermidine synthase and spermine synthase carry out polyamine biosynthesis.

GO:0006598

polyamine catabolic process

Polyamine N1-acetyltransferases and FAD polyamine oxidases carry out back-conversion.

PMID:9073064

Spermidine biosynthesis in Saccharomyces cerevisae: polyamine requirement of a null mutant of the SPE3 gene (spermidine synthase).

SPE3 is the only yeast spermidine synthase, and spermidine is essential.

we constructed a null mutant of this gene, spe3delta, which has no spermidine synthase activity and has an absolute requirement for spermidine or spermine for the growth.

PMID:9573363

Spermine is not essential for growth of Saccharomyces cerevisiae: identification of the SPE4 gene (spermine synthase) and characterization of a spe4 deletion mutant.

SPE4 is the yeast spermine synthase, and spermine is dispensable.

This mutant has neither spermine nor spermine synthase activity. Using the spe4 deletion mutant, we show that S. cerevisiae does not require spermine for growth

PMID:12670477

Yeast Fms1 is a FAD-utilizing polyamine oxidase.

Fms1 oxidises spermine and N1-acetylpolyamines, but not spermidine.

Biochemical characterization of Fms1 shows that it can oxidize spermine, N(1)-acetylspermine, N(1)-acetylspermidine, and N(8)-acetylspermidine, but not spermidine. The products of spermine oxidation are spermidine and 3-aminopropanal.

PMID:11154694

Saccharomyces cerevisiae is capable of de Novo pantothenic acid biosynthesis involving a novel pathway of beta-alanine production from spermine.

FMS1 and all SPE genes are needed for beta-alanine, which comes from spermine.

we found that all the enzymes of the polyamine pathway in yeast are necessary for beta-alanine biosynthesis; spe1Delta, spe2Delta, spe3Delta, and spe4Delta are all beta-alanine auxotrophs.

PMID:15723835

A yeast polyamine acetyltransferase.

PAA1 acetylates putrescine, spermidine and spermine, and lowers the spermine available for beta-alanine.

The recombinant Paa1 protein readily acetylates various polyamines such as putrescine, spermidine, and spermine.

PMID:15538383

Polyamines regulate their synthesis by inducing expression and blocking degradation of ODC antizyme.

Identifies S. cerevisiae OAZ1 antizyme, which is made by polyamine-regulated frameshifting and needed for proteasomal ODC degradation.

We show that synthesis of yeast AZ (Oaz1) involves polyamine-regulated frameshifting as well. Degradation of yeast ODC by the proteasome depends on Oaz1.

PMID:10775274

Conservation of polyamine regulation by translational frameshifting from yeast to mammals.

S. pombe antizyme (spa1) needs a +1 frameshift like mammalian antizyme.

As shown here, the yeast antizyme gene and several newly identified antizyme genes from different nematodes also require a ribosomal frameshift event for their expression.

PMID:14506228

Methylthioadenosine phosphorylase regulates ornithine decarboxylase by production of downstream metabolites.

The methionine salvage intermediate 4-methylthio-2-oxobutanoate represses ODC; meu1 deletion raises yeast ODC activity.

We show that in Saccharomyces cerevisiae the MEU1 gene encodes MTAP and that Meu1delta cells have an 8-fold increase in ODC activity, resulting in large elevations in polyamine pools.

file:human/ODC1/ODC1-ai-review.yaml

ODC1 gene review (human)

The ornithine-to-putrescine step (UniProtKB:P11926, GO:0004586) matches the completed human ODC1 review.

file:human/AMD1/AMD1-ai-review.yaml

AMD1 gene review (human)

The SAM-to-dcSAM step (UniProtKB:P17707, GO:0004014) matches the completed human AMD1 review.

file:human/SRM/SRM-ai-review.yaml

SRM gene review (human)

The putrescine-to-spermidine step (UniProtKB:P19623, GO:0004766) matches the completed human SRM review.

file:human/SMS/SMS-ai-review.yaml

SMS gene review (human)

The animal spermidine-to-spermine step (UniProtKB:P52788, GO:0016768) matches the completed human SMS review.

file:human/SAT1/SAT1-ai-review.yaml

SAT1 gene review (human)

The animal polyamine N1-acetylation step (UniProtKB:P21673, GO:0004145) matches the completed human SAT1 review.

file:human/PAOX/PAOX-ai-review.yaml

PAOX gene review (human)

The animal N1-acetylpolyamine oxidation step (UniProtKB:Q6QHF9, GO:0052903) matches the completed human PAOX review.

file:human/SMOX/SMOX-ai-review.yaml

SMOX gene review (human)

The animal direct spermine-to-spermidine oxidation step (UniProtKB:Q9NWM0, GO:0052901) matches the completed human SMOX review.

file:human/OAZ1/OAZ1-ai-review.yaml

OAZ1 gene review (human)

The antizyme regulator (UniProtKB:P54368, GO:0008073) matches the completed human OAZ1 review.

file:human/AZIN1/AZIN1-ai-review.yaml

AZIN1 gene review (human)

The antizyme inhibitor (UniProtKB:O14977, GO:0042978) matches the completed human AZIN1 review.

18Nodes

8Parts

4Variant Sets

9Variants

14Annotons

10Connections

Derived QC

Recommended-field compliance

80.0% recommended fields populated

knowledge_gaps[0] · provenance (0/1)

Module deep research

✗ none found

No MODULE:polyamine_metabolism 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.

ornithine_to_putrescine → putrescine_to_spermidine [NOT_CHECKED]
Putrescine from ODC (or agmatinase) is the acceptor substrate of spermidine synthase.
putrescine_to_spermidine → spermidine_to_spermine [NOT_CHECKED]
Spermidine is the spermidine synthase product and the spermine synthase acceptor.

Function consistency and core coverage

24 gene-function check(s) reflected in core functions · 0 conflict(s) · 1 evidence or coverage gap(s) (53 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.

Annoton	Participant	Function	Assessment
odc1_activity	SPE1 (S. cerevisiae) UniProtKB:P08432 Family Representative	ornithine decarboxylase activity GO:0004586	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
odc1_activity	spe1 (S. pombe, SPAC144.04c) UniProtKB:Q9UQW9 Family Representative	ornithine decarboxylase activity GO:0004586	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
odc1_activity	ODC1 (human) UniProtKB:P11926 Family Representative	ornithine decarboxylase activity GO:0004586	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
agmatinase_activity	speB (Escherichia coli K-12) UniProtKB:P60651 Family Representative	agmatinase activity GO:0008783	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
agmatinase_activity	agm1 (S. pombe, SPAC11D3.09) UniProtKB:Q10088 Family Representative	agmatinase activity GO:0008783	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
agmatinase_activity	agm2 (S. pombe, SPAPB24D3.03) UniProtKB:Q9C0Y9 Family Representative	agmatinase activity GO:0008783	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
agmatinase_activity	agm3 (S. pombe, SPBC8E4.03) UniProtKB:O42887 Family Representative	agmatinase activity GO:0008783	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
amd1_activity	SPE2 (S. cerevisiae) UniProtKB:P21182 Family Representative	adenosylmethionine decarboxylase activity GO:0004014	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
amd1_activity	spe2 (S. pombe, SPBP4H10.05c) UniProtKB:Q9P7E3 Family Representative	adenosylmethionine decarboxylase activity GO:0004014	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
amd1_activity	AMD1 (human) UniProtKB:P17707 Family Representative	adenosylmethionine decarboxylase activity GO:0004014	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
srm_activity	SPE3 (S. cerevisiae) UniProtKB:Q12074 Family Representative	spermidine synthase activity GO:0004766	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
srm_activity	srm1 (S. pombe, SPBC12C2.07c) UniProtKB:Q09741 Family Representative	spermidine synthase activity GO:0004766	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
srm_activity	SRM (human) UniProtKB:P19623 Family Representative	spermidine synthase activity GO:0004766	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
sms_activity	SMS (human) UniProtKB:P52788 Family Representative	spermine synthase activity GO:0016768	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
spe4_activity	SPE4 (S. cerevisiae) UniProtKB:Q12455 Family Representative	spermine synthase activity GO:0016768	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
sat1_activity	SAT1 (human) UniProtKB:P21673 Family Representative	diamine N-acetyltransferase activity GO:0004145	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
paa1_activity	PAA1 (S. cerevisiae) UniProtKB:Q12447 Family Representative	diamine N-acetyltransferase activity GO:0004145	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
paox_activity	PAOX (human) UniProtKB:Q6QHF9 Family Representative	N(1)-acetylpolyamine oxidase activity GO:0052903	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
smox_activity	SMOX (human) UniProtKB:Q9NWM0 Family Representative	spermine oxidase activity GO:0052901	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fms1_spermine_oxidase_activity	FMS1 (S. cerevisiae) UniProtKB:P50264 Family Representative	spermine oxidase activity GO:0052901	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
fms1_acetylpolyamine_oxidase_activity	FMS1 (S. cerevisiae) UniProtKB:P50264 Family Representative	N(1)-acetylpolyamine oxidase activity GO:0052903	Non Core Supported The review explicitly retains this function as non-core; promotion into core_functions is not implied.
oaz1_activity	OAZ1 (human) UniProtKB:P54368 Family Representative	ornithine decarboxylase inhibitor activity GO:0008073	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
oaz1_activity	spa1 (S. pombe, SPBC577.14c) UniProtKB:Q9USQ5 Family Representative	ornithine decarboxylase inhibitor activity GO:0008073	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
oaz1_activity	OAZ1 (S. cerevisiae) UniProtKB:Q02803 Family Representative	ornithine decarboxylase inhibitor activity GO:0008073	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
azin1_activity	AZIN1 (human) UniProtKB:O14977 Family Representative	ornithine decarboxylase activator activity GO:0042978	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
odc1_activity	ODC / group IV PLP decarboxylase family PANTHER:PTHR11482:SF42 Family	ornithine decarboxylase activity GO:0004586	Family Supported Family review supports GO:0004586 for PANTHER:PTHR11482:SF42. ODC subfamilies, plus AZIN2 (SF4), whose review accepts weak ODC activity. bacterial_putrescine_biosynthesis selects SF6; polyamine_metabolism selects the base family, which also takes in AZIN1.
odc1_activity	ODC / group IV PLP decarboxylase family PANTHER:PTHR11482:SF6 Family	ornithine decarboxylase activity GO:0004586	Family Supported Family review supports GO:0004586 for PANTHER:PTHR11482:SF6. ODC subfamilies, plus AZIN2 (SF4), whose review accepts weak ODC activity. bacterial_putrescine_biosynthesis selects SF6; polyamine_metabolism selects the base family, which also takes in AZIN1.
odc1_activity	ODC / group IV PLP decarboxylase family PANTHER:PTHR11482:SF63 Family	ornithine decarboxylase activity GO:0004586	Family Supported Family review supports GO:0004586 for PANTHER:PTHR11482:SF63. ODC subfamilies, plus AZIN2 (SF4), whose review accepts weak ODC activity. bacterial_putrescine_biosynthesis selects SF6; polyamine_metabolism selects the base family, which also takes in AZIN1.
agmatinase_activity	ureohydrolase (arginase/agmatinase) family PANTHER:PTHR11358:SF26 Family	agmatinase activity GO:0008783	Family Supported Family review supports GO:0008783 for PANTHER:PTHR11358:SF26. Agmatinase activity is supported in SF30 (S. pombe agmatinases), in the plant ARGAH2 subfamily SF32 (purified Arabidopsis ARGAH2 turns over agmatine, PMID:28716421; clade-level extension rests on the conserved plant ARGAH substrate-binding architecture, PMID:32754173), and in SF26 for the SpeB agmatinases (E. coli SpeB, purified enzyme). SF26 is functionally mixed, so its grant carries member exceptions for every Swiss-Prot member with evidence against agmatinase activity: formimidoylglutamases (HutG), proclavaminate amidinohydrolase (Pah), guanidine hydrolase (GdmH), guanidinobutyrases (GbuA, GBU1, Gbh), guanidinopropionase (GpuA), the APAUHs of Synechocystis and Thermus, and the vertebrate AGMAT guanidino acid hydrolases. Not excepted: Thermococcus TK0882, an APAUH that also converts agmatine to putrescine; the plant arginases placed in SF26 (Arabidopsis ARGAH1 has dual arginase/agmatinase evidence); and the uncharacterized Methanothermus P19268. No family-wide grant and no extension to the SF41 arginases or SF35 formiminoglutamases is made.
agmatinase_activity	ureohydrolase (arginase/agmatinase) family PANTHER:PTHR11358:SF30 Family	agmatinase activity GO:0008783	Family Supported Family review supports GO:0008783 for PANTHER:PTHR11358:SF30. Agmatinase activity is supported in SF30 (S. pombe agmatinases), in the plant ARGAH2 subfamily SF32 (purified Arabidopsis ARGAH2 turns over agmatine, PMID:28716421; clade-level extension rests on the conserved plant ARGAH substrate-binding architecture, PMID:32754173), and in SF26 for the SpeB agmatinases (E. coli SpeB, purified enzyme). SF26 is functionally mixed, so its grant carries member exceptions for every Swiss-Prot member with evidence against agmatinase activity: formimidoylglutamases (HutG), proclavaminate amidinohydrolase (Pah), guanidine hydrolase (GdmH), guanidinobutyrases (GbuA, GBU1, Gbh), guanidinopropionase (GpuA), the APAUHs of Synechocystis and Thermus, and the vertebrate AGMAT guanidino acid hydrolases. Not excepted: Thermococcus TK0882, an APAUH that also converts agmatine to putrescine; the plant arginases placed in SF26 (Arabidopsis ARGAH1 has dual arginase/agmatinase evidence); and the uncharacterized Methanothermus P19268. No family-wide grant and no extension to the SF41 arginases or SF35 formiminoglutamases is made.
amd1_activity	eukaryotic S-adenosylmethionine decarboxylase PANTHER:PTHR11570:SF0 Family	adenosylmethionine decarboxylase activity GO:0004014	Family Supported Family review supports GO:0004014 for PANTHER:PTHR11570:SF0. All catalytic subfamilies, not the prozyme (SF2). polyamine_metabolism selects the base family.
amd1_activity	eukaryotic S-adenosylmethionine decarboxylase PANTHER:PTHR11570:SF15 Family	adenosylmethionine decarboxylase activity GO:0004014	Family Supported Family review supports GO:0004014 for PANTHER:PTHR11570:SF15. All catalytic subfamilies, not the prozyme (SF2). polyamine_metabolism selects the base family.
amd1_activity	eukaryotic S-adenosylmethionine decarboxylase PANTHER:PTHR11570:SF24 Family	adenosylmethionine decarboxylase activity GO:0004014	Family Supported Family review supports GO:0004014 for PANTHER:PTHR11570:SF24. All catalytic subfamilies, not the prozyme (SF2). polyamine_metabolism selects the base family.
amd1_activity	eukaryotic S-adenosylmethionine decarboxylase PANTHER:PTHR11570:SF32 Family	adenosylmethionine decarboxylase activity GO:0004014	Family Supported Family review supports GO:0004014 for PANTHER:PTHR11570:SF32. All catalytic subfamilies, not the prozyme (SF2). polyamine_metabolism selects the base family.
amd1_activity	eukaryotic S-adenosylmethionine decarboxylase PANTHER:PTHR11570:SF34 Family	adenosylmethionine decarboxylase activity GO:0004014	Family Supported Family review supports GO:0004014 for PANTHER:PTHR11570:SF34. All catalytic subfamilies, not the prozyme (SF2). polyamine_metabolism selects the base family.
amd1_activity	eukaryotic S-adenosylmethionine decarboxylase PANTHER:PTHR11570:SF36 Family	adenosylmethionine decarboxylase activity GO:0004014	Family Supported Family review supports GO:0004014 for PANTHER:PTHR11570:SF36. All catalytic subfamilies, not the prozyme (SF2). polyamine_metabolism selects the base family.
amd1_activity	eukaryotic S-adenosylmethionine decarboxylase PANTHER:PTHR11570:SF38 Family	adenosylmethionine decarboxylase activity GO:0004014	Family Supported Family review supports GO:0004014 for PANTHER:PTHR11570:SF38. All catalytic subfamilies, not the prozyme (SF2). polyamine_metabolism selects the base family.
srm_activity	aminopropyltransferase (spermidine synthase) family PANTHER:PTHR11558:SF11 Family	spermidine synthase activity GO:0004766	Family Supported Family review supports GO:0004766 for PANTHER:PTHR11558:SF11. Spermidine synthase subfamilies (SF11, SF43), with SPE4 as a member exception. polyamine_metabolism selects the base family, which also takes in the PMTs.
srm_activity	aminopropyltransferase (spermidine synthase) family PANTHER:PTHR11558:SF43 Family	spermidine synthase activity GO:0004766	Family Supported Family review supports GO:0004766 for PANTHER:PTHR11558:SF43. Spermidine synthase subfamilies (SF11, SF43), with SPE4 as a member exception. polyamine_metabolism selects the base family, which also takes in the PMTs.
sms_activity	SMS spermine synthase family PANTHER:PTHR46315 Family	spermine synthase activity GO:0016768	Family Supported Family review supports GO:0016768 FAMILY_WIDE. Asserted by polyamine_metabolism; accepted by SMS.
spe4_activity	aminopropyltransferase family (SPE3/SPE4 paralogues) PANTHER:PTHR11558:SF11 Family	spermine synthase activity GO:0016768	Family Supported Family review supports GO:0016768 for PANTHER:PTHR11558:SF11. Spermine synthases: S. cerevisiae SPE4 in SF11 and plant SPMS in SF25. polyamine_metabolism asserts it for SPE4 on the base family.
spe4_activity	aminopropyltransferase family (SPE3/SPE4 paralogues) PANTHER:PTHR11558:SF25 Family	spermine synthase activity GO:0016768	Family Supported Family review supports GO:0016768 for PANTHER:PTHR11558:SF25. Spermine synthases: S. cerevisiae SPE4 in SF11 and plant SPMS in SF25. polyamine_metabolism asserts it for SPE4 on the base family.
sat1_activity	SAT1 / GNAT polyamine N-acetyltransferase family PANTHER:PTHR10545:SF36 Family	diamine N-acetyltransferase activity GO:0004145	Family Supported Family review supports GO:0004145 for PANTHER:PTHR10545:SF36. SAT1 (SF36) only. polyamine_metabolism selects the base family, which also takes in SAT2 and the plant feruloyltransferases.
paa1_activity	arylalkylamine N-acetyltransferase-related GNAT PANTHER:PTHR10908 Family	diamine N-acetyltransferase activity GO:0004145	Family Function Unreviewed Family review leaves GO:0004145 UNRESOLVED. polyamine_metabolism asserts it on the base family for S. cerevisiae PAA1, whose review accepts it. Whether vertebrate AANAT has diamine N-acetyltransferase activity is not established, so the scope is left unresolved.
paox_activity	FAD flavin amine oxidase family PANTHER:PTHR10742:SF405 Family	N(1)-acetylpolyamine oxidase activity GO:0052903	Family Supported Family review supports GO:0052903 for PANTHER:PTHR10742:SF405. PAOX (SF405), selected by polyamine_metabolism, and S. cerevisiae FMS1 (SF410). polyamine_metabolism also asserts it on the base family for FMS1, which is far too broad.
smox_activity	FAD flavin amine oxidase family PANTHER:PTHR10742:SF416 Family	spermine oxidase activity GO:0052901	Family Supported Family review supports GO:0052901 for PANTHER:PTHR10742:SF416. SMOX (SF416), selected by polyamine_metabolism, and FMS1 (SF410).
fms1_spermine_oxidase_activity	FAD flavin amine oxidase family PANTHER:PTHR10742:SF416 Family	spermine oxidase activity GO:0052901	Family Supported Family review supports GO:0052901 for PANTHER:PTHR10742:SF416. SMOX (SF416), selected by polyamine_metabolism, and FMS1 (SF410).
fms1_spermine_oxidase_activity	FAD flavin amine oxidase family PANTHER:PTHR10742:SF410 Family	spermine oxidase activity GO:0052901	Family Supported Family review supports GO:0052901 for PANTHER:PTHR10742:SF410. SMOX (SF416), selected by polyamine_metabolism, and FMS1 (SF410).
fms1_acetylpolyamine_oxidase_activity	FAD flavin amine oxidase family PANTHER:PTHR10742:SF405 Family	N(1)-acetylpolyamine oxidase activity GO:0052903	Family Supported Family review supports GO:0052903 for PANTHER:PTHR10742:SF405. PAOX (SF405), selected by polyamine_metabolism, and S. cerevisiae FMS1 (SF410). polyamine_metabolism also asserts it on the base family for FMS1, which is far too broad.
fms1_acetylpolyamine_oxidase_activity	FAD flavin amine oxidase family PANTHER:PTHR10742:SF410 Family	N(1)-acetylpolyamine oxidase activity GO:0052903	Family Supported Family review supports GO:0052903 for PANTHER:PTHR10742:SF410. PAOX (SF405), selected by polyamine_metabolism, and S. cerevisiae FMS1 (SF410). polyamine_metabolism also asserts it on the base family for FMS1, which is far too broad.
oaz1_activity	ornithine decarboxylase antizyme family PANTHER:PTHR10279 Family	ornithine decarboxylase inhibitor activity GO:0008073	Family Supported Family review supports GO:0008073 FAMILY_WIDE. Asserted by polyamine_metabolism; accepted by every reviewed member (human and rat OAZ1, S. pombe spa1, Pristionchus oaz).
azin1_activity	AZIN / antizyme inhibitor (inactive ODC homologue) PANTHER:PTHR11482:SF7 Family	ornithine decarboxylase activator activity GO:0042978	Family Supported Family review supports GO:0042978 for PANTHER:PTHR11482:SF7. The antizyme inhibitors (SF7, SF4), as polyamine_metabolism asserts for AZIN1.
azin1_activity	AZIN / antizyme inhibitor (inactive ODC homologue) PANTHER:PTHR11482:SF4 Family	ornithine decarboxylase activator activity GO:0042978	Family Supported Family review supports GO:0042978 for PANTHER:PTHR11482:SF4. The antizyme inhibitors (SF7, SF4), as polyamine_metabolism asserts for AZIN1.

Feedback loops (advisory, prose-driven: a regulator counts as "feedback" when its own description says so)

✓ every negative regulator described as feedback has an upstream edge closing the loop.

antizyme ⊣ ornithine_to_putrescine [closed]
antizyme is regulated by putrescine_to_spermidine: feedback loop closed
antizyme_inhibitor ⊣ antizyme [input]
antizyme_inhibitor is a negative regulator with no upstream edge (not described as feedback)

Gene-review completeness (24/24 grounded genes reviewed)

24 complete review(s) · 7 with deep research · 0 missing review · 17 reviewed but lacking deep research

Gene	Review	Complete	Deep research
AMD1 P17707	✓	✓	✗
AZIN1 O14977	✓	✓	✗
FMS1 P50264	✓	✓	✓
OAZ1 P54368	✓	✓	✗
OAZ1 Q02803	✓	✓	✓
ODC1 P11926	✓	✓	✗
PAA1 Q12447	✓	✓	✓
PAOX Q6QHF9	✓	✓	✗
SAT1 P21673	✓	✓	✗
SMOX Q9NWM0	✓	✓	✗
SMS P52788	✓	✓	✗
spa1 Q9USQ5	✓	✓	✗
SPAC11D3.09 Q10088	✓	✓	✗
SPAPB24D3.03 Q9C0Y9	✓	✓	✗
SPBC12C2.07c Q09741	✓	✓	✗
SPBC8E4.03 O42887	✓	✓	✗
SPE1 P08432	✓	✓	✓
spe1 Q9UQW9	✓	✓	✗
SPE2 P21182	✓	✓	✓
spe2 Q9P7E3	✓	✓	✗
SPE3 Q12074	✓	✓	✓
SPE4 Q12455	✓	✓	✓
speB P60651	✓	✓	✗
SRM P19623	✓	✓	✗

Tree

Eukaryotic polyamine metabolism (biosynthesis, back-conversion, antizyme regulation)Metabolic Pathwaypolyamine_metabolism

Parts
1. 1. putrescine synthesis (rate-limiting)
2. Putrescine formationReactionornithine_to_putrescine
  
  Variants
  1. Putrescine-forming routes by route variant (One Or More)
    
    Ornithine decarboxylase (all eukaryotes examined)Reactionodc_route
    
    Annotons
    
    Ornithine decarboxylase (ODC1/SPE1/spe1) Family: ODC / group IV PLP decarboxylase family
    
    Agmatinase (agmatine ureohydrolase; bacteria, asserted in S. pombe)Reactionagmatinase_route
    
    Annotons
    
    Agmatinase (SpeB / agm1-3) Family: ureohydrolase (arginase/agmatinase) family
3. 2. aminopropyl donor synthesis
4. S-adenosylmethionine decarboxylaseReactionsam_decarboxylation
  
  Annotons
  - Adenosylmethionine decarboxylase, pyruvoyl-dependent (AMD1/SPE2/spe2) Family: eukaryotic S-adenosylmethionine decarboxylase
5. 3. spermidine synthesis
6. Spermidine synthaseReactionputrescine_to_spermidine
  
  Annotons
  - Spermidine synthase (SRM/SPE3/srm1) Family: aminopropyltransferase (spermidine synthase) family
7. 4. spermine synthesis (not essential in yeast) optional
8. Spermine synthaseReactionspermidine_to_spermine
  
  Variants
  1. Spermine synthase lineages by enzyme family / lineage (Exactly One)
    
    Animal-type spermine synthase (SMS family)Reactionanimal_sms_variant
    
    Annotons
    
    Spermine synthase (SMS, human) Family: SMS spermine synthase family
    
    Fungal SPE4-type spermine synthase (SPE3 paralogue)Reactionfungal_spe4_variant
    
    Annotons
    
    Spermine synthase SPE4 (S. cerevisiae) Family: aminopropyltransferase family (SPE3/SPE4 paralogues)
9. 5. polyamine N1-acetylation (catabolism) optional
10. Polyamine N-acetylationReactionpolyamine_acetylation
  
  Variants
  1. Polyamine N-acetyltransferase lineages by enzyme family / lineage (One Or More)
    
    Animal SAT1 (diamine N-acetyltransferase family)Reactionanimal_sat1_variant
    
    Annotons
    
    Spermidine/spermine N1-acetyltransferase (SAT1, human) Family: SAT1 / GNAT polyamine N-acetyltransferase family
    
    Yeast PAA1 (AANAT-related GNAT)Reactionfungal_paa1_variant
    
    Annotons
    
    Polyamine N-acetyltransferase PAA1 (S. cerevisiae) Family: arylalkylamine N-acetyltransferase-related GNAT
11. 6. polyamine oxidation (back-conversion) optional
12. FAD-dependent polyamine oxidationReactionpolyamine_oxidation
  
  Variants
  1. Polyamine oxidase lineages by enzyme lineage / substrate specificity (One Or More)
    
    Animal PAOX (N1-acetylpolyamine oxidase, peroxisomal)Reactionanimal_paox_variant
    
    Annotons
    
    N1-acetylpolyamine oxidase (PAOX, human) Family: FAD flavin amine oxidase family
    
    Animal SMOX (free spermine oxidase)Reactionanimal_smox_variant
    
    Annotons
    
    Spermine oxidase (SMOX, human) Family: FAD flavin amine oxidase family
    
    Yeast Fms1 (oxidises both spermine and N1-acetylpolyamines)Reactionfungal_fms1_variant
    
    Annotons
    
    Fms1 spermine oxidase activity Family: FAD flavin amine oxidase family
    
    Fms1 N1-acetylpolyamine oxidase activity Family: FAD flavin amine oxidase family
13. 7. antizyme feedback (ODC inhibition and degradation)
14. Ornithine decarboxylase antizymeRegulatory Stepantizyme
  
  Annotons
  - ODC antizyme (OAZ1/Oaz1/spa1) Family: ornithine decarboxylase antizyme family
15. 8. antizyme inhibition (ODC activation; vertebrates) optional
16. Antizyme inhibitorRegulatory Stepantizyme_inhibitor
  
  Annotons
  - Antizyme inhibitor (AZIN1; catalytically dead ODC homologue) Family: AZIN / antizyme inhibitor (inactive ODC homologue)

Details

Context

cytosolGO:0005829

Eukaryotic polyamine metabolism (biosynthesis, back-conversion, antizyme regulation)Metabolic Pathwaypolyamine_metabolism

ornithine (or agmatine) -> putrescine -> spermidine [-> spermine], using dcSAM from SAM; spermine / N1-acetylpolyamines -> spermidine -> putrescine by back-conversion; antizyme feedback on ODC.

polyamine biosynthetic processGO:0006596 polyamine catabolic processGO:0006598

Context

cytosolGO:0005829

Generalisation (crosswalk GENERALIZE, scope: eukaryotic polyamine biosynthesis). The original human-grounded module (nine human reviews: ODC1, AMD1, SRM, SMS, SAT1, PAOX, SMOX, OAZ1, AZIN1) is kept in full. The animal-specific enzymes are now lineage variants: SMS-family spermine synthase, SAT1, PAOX, SMOX and the AZIN1 inhibitor step. Fungal exemplars were added for every conserved step. Spermine synthesis, catabolism and the antizyme inhibitor are marked optional because spermine is dispensable in S. cerevisiae (PMID:9573363), S. pombe has no FMS1-like oxidase, and antizyme inhibitors are vertebrate-specific. The crosswalk rationale called FMS1 orthologous to the human oxidases. It is a member of the same FAD amine oxidase family but combines the SMOX and PAOX substrate ranges in one enzyme (PMID:12670477), so it is modelled as its own variant rather than as an orthologue of either. YeastCyc corrections: the four biosynthetic assignments (SPE1, SPE2, SPE3, SPE4; all cytosolic) are kept and agree with the committed SPE2, SPE3 and SPE4 reviews. SPE3 is the only spermidine synthase (PMID:9073064). The PAINT IBA spermidine synthase annotation on SPE4 is over-propagation from SPE3, and SPE4 is modelled with spermine synthase activity only. YeastCyc has no S. cerevisiae polyamine catabolism or regulation. Added here: FMS1 polyamine oxidase (PMID:12670477), which also supplies beta-alanine (PMID:11154694); PAA1 polyamine acetyltransferase (PMID:15723835); and OAZ1 antizyme (PMID:15538383). Regulatory cross-talk: deletion of MEU1 in the methionine salvage cycle raises yeast ODC activity about 8-fold, and the salvage intermediate 4-methylthio-2-oxobutanoate represses ODC (PMID:14506228). Each aminopropyl transfer releases MTA, the entry substrate of methionine_salvage_mta_cycle. GO-CAM notes: (1) PomBase model gomodel:67b1629100004168 gives srm1 (SPBC12C2.07c) both spermidine synthase (67b1629100004357) and spermine synthase (67b1629100004380) activities. S. pombe has no separate SMS or SPE4-like gene, and srm1 is used here only as a spermidine synthase exemplar. Whether S. pombe makes spermine through srm1 is left open. (2) The same model includes upstream supply activities (sam1 methionine adenosyltransferase; car1 and aru1 arginases; ort1 mitochondrial ornithine transporter), which are outside the module boundary, and three agmatinases (agm1-3) placed in putrescine biosynthesis. (3) The YeastPathways models agree with this module (MFs GO:0004586, GO:0004014, GO:0004766, GO:0016768; cytosol). Out of scope: eIF5A hypusination (consumes spermidine), polyamine transport (e.g. yeast TPO and DUR3 transporters, human ATP13A3), and the beta-alanine to pantothenate steps (coenzyme_a_biosynthesis). Diseases (human): ODC1 gain of function causes Bachmann-Bupp syndrome; SMS deficiency causes Snyder-Robinson syndrome.

Connections

ornithine_to_putrescine -> putrescine_to_spermidine Precedes

sam_decarboxylation -> putrescine_to_spermidine Provides Input For

AdoMetDC supplies the dcSAM aminopropyl donor used by spermidine synthase.

sam_decarboxylation -> spermidine_to_spermine Provides Input For

AdoMetDC also supplies the dcSAM used by spermine synthase.

putrescine_to_spermidine -> spermidine_to_spermine Precedes

spermidine_to_spermine -> polyamine_acetylation Provides Input For

Spermine (and spermidine) are N-acetylated by SAT1 or PAA1.

spermidine_to_spermine -> polyamine_oxidation Provides Input For

Free spermine is oxidised directly to spermidine by SMOX or Fms1.

polyamine_acetylation -> polyamine_oxidation Provides Input For

N1-acetylpolyamines are oxidised by PAOX (animals) or Fms1 (yeast), completing back-conversion.

putrescine_to_spermidine -> antizyme Positively Regulates

Polyamines (spermidine) stimulate the +1 frameshift needed to make antizyme and, in yeast, block Oaz1 degradation, closing the feedback loop (PMID:15538383).

antizyme -> ornithine_to_putrescine Negatively Regulates

Antizyme binds ODC, inhibits it and targets it for ubiquitin-independent proteasomal degradation.

antizyme_inhibitor -> antizyme Negatively Regulates

AZIN1 sequesters antizyme, releasing active ODC.

Part 1: putrescine synthesis (rate-limiting)

Putrescine formationReactionornithine_to_putrescine

Variant set: Putrescine-forming routes by route variant (One Or More)

Ornithine decarboxylase (all eukaryotes examined)Reactionodc_route

Annotons

Ornithine decarboxylase (ODC1/SPE1/spe1)

odc1_activity

Participant: Family: ODC / group IV PLP decarboxylase family

Family:

ODC / group IV PLP decarboxylase family Restricted to the ODC subfamilies of PTHR11482: SF42 (vertebrate ODC1), SF6 (the non-vertebrate ODCs of fungi, Dictyostelium, invertebrates, plants and some bacteria, including SPE1 and spe1) and SF63 (an ODC subfamily whose indexed member is the Nicotiana attenuata ODC A0A314KUM9). The catalytically dead antizyme inhibitors (AZIN1 in SF7, AZIN2 in SF4) are left out; they are the separate antizyme-inhibitor annoton.

Representative Members: SPE1 (S. cerevisiae)UniProtKB:P08432 spe1 (S. pombe, SPAC144.04c)UniProtKB:Q9UQW9 ODC1 (human)UniProtKB:P11926

Required Function:

ornithine decarboxylase activityGO:0004586

Function

ornithine decarboxylase activityGO:0004586

Substrates: L-ornithine (PLP cofactor)

Products: putrescine CO2

Locations

cytosolGO:0005829

Decarboxylates ornithine to putrescine (rate-limiting).

Agmatinase (agmatine ureohydrolase; bacteria, asserted in S. pombe)Reactionagmatinase_route

Hydrolysis of agmatine to putrescine and urea. In bacteria the agmatine comes from biosynthetic arginine decarboxylase (e.g. E. coli SpeA), which is outside this module. S. pombe has three putative agmatinases in the PomBase model but no arginine decarboxylase family (PTHR43295) member, so where its agmatine comes from is unknown (see knowledge gaps).

Annotons

Agmatinase (SpeB / agm1-3)

agmatinase_activity

Participant: Family: ureohydrolase (arginase/agmatinase) family

Family:

ureohydrolase (arginase/agmatinase) family Restricted to the agmatinase subfamilies of the ureohydrolase family PTHR11358: SF26 (speB and S. pombe agm3) and SF30 (S. pombe agm1 and agm2). The arginase subfamilies are left out. SF26 is mixed, and the PTHR11358 family review excepts its non-agmatinase members, including the vertebrate AGMAT proteins, which were reassigned as guanidino acid hydrolases with no agmatine hydrolysis (PubMed:36543883).

Representative Members: speB (Escherichia coli K-12)UniProtKB:P60651 agm1 (S. pombe, SPAC11D3.09)UniProtKB:Q10088 agm2 (S. pombe, SPAPB24D3.03)UniProtKB:Q9C0Y9 agm3 (S. pombe, SPBC8E4.03)UniProtKB:O42887

Required Function:

agmatinase activityGO:0008783

Function

agmatinase activityGO:0008783

Substrates: agmatine water

Products: putrescine urea

The PomBase model places the S. pombe agmatinases on the cytoplasmic side of the ER membrane (GO:0098554).

Part 2: aminopropyl donor synthesis

S-adenosylmethionine decarboxylaseReactionsam_decarboxylation

Annotons

Adenosylmethionine decarboxylase, pyruvoyl-dependent (AMD1/SPE2/spe2)

amd1_activity

Participant: Family: eukaryotic S-adenosylmethionine decarboxylase

Family:

eukaryotic S-adenosylmethionine decarboxylase

Representative Members: SPE2 (S. cerevisiae)UniProtKB:P21182 spe2 (S. pombe, SPBP4H10.05c)UniProtKB:Q9P7E3 AMD1 (human)UniProtKB:P17707

Required Function:

adenosylmethionine decarboxylase activityGO:0004014

Function

adenosylmethionine decarboxylase activityGO:0004014

Substrates: S-adenosyl-L-methionine (pyruvoyl cofactor)

Products: S-adenosyl 3-(methylsulfanyl)propylamine (dcSAM) CO2

Locations

cytosolGO:0005829

Makes decarboxylated SAM, the sole aminopropyl donor.

Part 3: spermidine synthesis

Spermidine synthaseReactionputrescine_to_spermidine

Annotons

Spermidine synthase (SRM/SPE3/srm1)

srm_activity

Participant: Family: aminopropyltransferase (spermidine synthase) family

Family:

aminopropyltransferase (spermidine synthase) family

Representative Members: SPE3 (S. cerevisiae)UniProtKB:Q12074 srm1 (S. pombe, SPBC12C2.07c)UniProtKB:Q09741 SRM (human)UniProtKB:P19623

Required Function:

spermidine synthase activityGO:0004766

Function

spermidine synthase activityGO:0004766

Substrates: putrescine decarboxylated SAM (dcSAM)

Products: spermidine 5'-methylthioadenosine (MTA)

Locations

cytosolGO:0005829

Aminopropylates putrescine to spermidine.

Part 4: spermine synthesis (not essential in yeast) (optional)

Spermine is dispensable in S. cerevisiae (PMID:9573363). S. pombe has no separate spermine synthase gene (see notes).

Spermine synthaseReactionspermidine_to_spermine

Variant set: Spermine synthase lineages by enzyme family / lineage (Exactly One)

Animal-type spermine synthase (SMS family)Reactionanimal_sms_variant

Annotons

Spermine synthase (SMS, human)

sms_activity

Participant: Family: SMS spermine synthase family

Family:

SMS spermine synthase familyPANTHER:PTHR46315

Representative Members: SMS (human)UniProtKB:P52788

Required Function:

spermine synthase activityGO:0016768

Function

spermine synthase activityGO:0016768

Substrates: spermidine decarboxylated SAM (dcSAM)

Products: spermine 5'-methylthioadenosine (MTA)

Locations

cytosolGO:0005829

Fungal SPE4-type spermine synthase (SPE3 paralogue)Reactionfungal_spe4_variant

Annotons

Spermine synthase SPE4 (S. cerevisiae)

spe4_activity

Participant: Family: aminopropyltransferase family (SPE3/SPE4 paralogues)

Family:

aminopropyltransferase family (SPE3/SPE4 paralogues) SPE4 is in the same PANTHER family and subfamily as SPE3 (PTHR11558:SF11), so required_function, not the family, separates the two roles.

Representative Members: SPE4 (S. cerevisiae)UniProtKB:Q12455

Required Function:

spermine synthase activityGO:0016768

Function

spermine synthase activityGO:0016768

Substrates: spermidine decarboxylated SAM (dcSAM)

Products: spermine 5'-methylthioadenosine (MTA)

Locations

cytosolGO:0005829

Part 5: polyamine N1-acetylation (catabolism) (optional)

Polyamine N-acetylationReactionpolyamine_acetylation

Variant set: Polyamine N-acetyltransferase lineages by enzyme family / lineage (One Or More)

Animal SAT1 (diamine N-acetyltransferase family)Reactionanimal_sat1_variant

Annotons

Spermidine/spermine N1-acetyltransferase (SAT1, human)

sat1_activity

Participant: Family: SAT1 / GNAT polyamine N-acetyltransferase family

Family:

SAT1 / GNAT polyamine N-acetyltransferase family

Representative Members: SAT1 (human)UniProtKB:P21673

Required Function:

diamine N-acetyltransferase activityGO:0004145

Function

diamine N-acetyltransferase activityGO:0004145

Substrates: spermine / spermidine acetyl-CoA

Products: N1-acetylspermine / N1-acetylspermidine coenzyme A

Locations

cytosolGO:0005829

N1-acetylates spermine/spermidine, committing them to PAOX back-conversion or export.

Yeast PAA1 (AANAT-related GNAT)Reactionfungal_paa1_variant

Annotons

Polyamine N-acetyltransferase PAA1 (S. cerevisiae)

paa1_activity

Participant: Family: arylalkylamine N-acetyltransferase-related GNAT

Family:

arylalkylamine N-acetyltransferase-related GNATPANTHER:PTHR10908 Not homologous at family level to SAT1; PAA1 is in the AANAT-related family (PTHR10908:SF0). The S. pombe member SPAC9.02c (Q9UT25) is uncharacterised and not used.

Representative Members: PAA1 (S. cerevisiae)UniProtKB:Q12447

Required Function:

diamine N-acetyltransferase activityGO:0004145

Function

diamine N-acetyltransferase activityGO:0004145

Substrates: putrescine / spermidine / spermine acetyl-CoA

Products: N-acetylated polyamines coenzyme A

Overexpression lowers spermine and causes a requirement for beta-alanine or pantothenate, so PAA1 competes with the Fms1 beta-alanine route rather than feeding it (PMID:15723835). The in vivo regiochemistry (N1 versus N8) is not established.

Part 6: polyamine oxidation (back-conversion) (optional)

FAD-dependent polyamine oxidationReactionpolyamine_oxidation

Variant set: Polyamine oxidase lineages by enzyme lineage / substrate specificity (One Or More)

Animal PAOX (N1-acetylpolyamine oxidase, peroxisomal)Reactionanimal_paox_variant

Annotons

N1-acetylpolyamine oxidase (PAOX, human)

paox_activity

Participant: Family: FAD flavin amine oxidase family

Family:

FAD flavin amine oxidase familyPANTHER:PTHR10742:SF405

Representative Members: PAOX (human)UniProtKB:Q6QHF9

Required Function:

N(1)-acetylpolyamine oxidase activityGO:0052903

Function

N(1)-acetylpolyamine oxidase activityGO:0052903

Substrates: N1-acetylspermine / N1-acetylspermidine O2 (FAD)

Products: spermidine / putrescine 3-acetamidopropanal + H2O2

Locations

peroxisomal matrixGO:0005782

Animal SMOX (free spermine oxidase)Reactionanimal_smox_variant

Annotons

Spermine oxidase (SMOX, human)

smox_activity

Participant: Family: FAD flavin amine oxidase family

Family:

FAD flavin amine oxidase familyPANTHER:PTHR10742:SF416

Representative Members: SMOX (human)UniProtKB:Q9NWM0

Required Function:

spermine oxidase activityGO:0052901

Function

spermine oxidase activityGO:0052901

Substrates: spermine O2 (FAD)

Products: spermidine 3-aminopropanal + H2O2

Locations

cytosolGO:0005829

Yeast Fms1 (oxidises both spermine and N1-acetylpolyamines)Reactionfungal_fms1_variant

One enzyme does both animal oxidase reactions. Spermine oxidation gives 3-aminopropanal, which is oxidised to beta-alanine for pantothenate and CoA synthesis (PMID:11154694; see coenzyme_a_biosynthesis).

Annotons

Fms1 spermine oxidase activity

fms1_spermine_oxidase_activity

Participant: Family: FAD flavin amine oxidase family

Family:

FAD flavin amine oxidase family Fms1 falls in subfamily PTHR10742:SF410, named after the S. pombe histone demethylase lsd2. The S. pombe members of that subfamily (lsd1, lsd2) are histone demethylases, so S. pombe has no Fms1 orthologue.

Representative Members: FMS1 (S. cerevisiae)UniProtKB:P50264

Required Function:

spermine oxidase activityGO:0052901

Function

spermine oxidase activityGO:0052901

Substrates: spermine O2 (FAD)

Products: spermidine 3-aminopropanal + H2O2

Processes

beta-alanine biosynthetic processGO:0019483

Fms1 N1-acetylpolyamine oxidase activity

fms1_acetylpolyamine_oxidase_activity

Participant: Family: FAD flavin amine oxidase family

Family:

FAD flavin amine oxidase family

Representative Members: FMS1 (S. cerevisiae)UniProtKB:P50264

Required Function:

N(1)-acetylpolyamine oxidase activityGO:0052903

Function

N(1)-acetylpolyamine oxidase activityGO:0052903

Substrates: N1-acetylspermine / N1-acetylspermidine O2 (FAD)

Products: spermidine / putrescine 3-acetamidopropanal + H2O2

Part 7: antizyme feedback (ODC inhibition and degradation)

Ornithine decarboxylase antizymeRegulatory Stepantizyme

Annotons

ODC antizyme (OAZ1/Oaz1/spa1)

oaz1_activity

Participant: Family: ornithine decarboxylase antizyme family

Family:

ornithine decarboxylase antizyme familyPANTHER:PTHR10279 Fungal antizymes are highly divergent. S. cerevisiae Oaz1 was missed by early HMM searches (PMID:10871270) and has no PANTHER assignment.

Representative Members: OAZ1 (human)UniProtKB:P54368 spa1 (S. pombe, SPBC577.14c)UniProtKB:Q9USQ5 OAZ1 (S. cerevisiae)UniProtKB:Q02803

Function

ornithine decarboxylase inhibitor activityGO:0008073

Locations

cytosolGO:0005829

Non-catalytic feedback regulator. A polyamine-stimulated +1 ribosomal frameshift is needed to make it (PMID:10775274, PMID:15538383). It binds ODC, inhibits it and targets it for ubiquitin-independent 26S proteasomal degradation. In mammals it also inhibits polyamine uptake. In yeast, polyamines also protect Oaz1 from its own ubiquitin-dependent degradation.

Part 8: antizyme inhibition (ODC activation; vertebrates) (optional)

Antizyme inhibitorRegulatory Stepantizyme_inhibitor

Annotons

Antizyme inhibitor (AZIN1; catalytically dead ODC homologue)

azin1_activity

Participant: Family: AZIN / antizyme inhibitor (inactive ODC homologue)

Family:

AZIN / antizyme inhibitor (inactive ODC homologue)

Representative Members: AZIN1 (human)UniProtKB:O14977

Required Function:

ornithine decarboxylase activator activityGO:0042978

Function

ornithine decarboxylase activator activityGO:0042978

Locations

cytosolGO:0005829

Has no ornithine decarboxylase activity. Binds antizyme more tightly than ODC does, so it sequesters antizyme and frees active ODC. No yeast counterpart is known.