L-methionine salvage from 5'-methylthioadenosine (MTA cycle)

The methionine salvage pathway, or 5'-methylthioadenosine (MTA) cycle, regenerates L-methionine from MTA, the by-product of S-adenosylmethionine (SAM) use in polyamine synthesis (and, in plants, ethylene synthesis). The methylthio group of MTA and carbons 2-5 of its ribose become the methionine skeleton, so the cycle recovers reduced sulfur that is costly to assimilate, and it also clears MTA, which inhibits spermidine synthase. MTA is first converted to S-methyl-5-thio-alpha-D-ribose 1-phosphate (MTR-1-P), either directly by MTA phosphorylase (eukaryotes and many bacteria) or by MTA nucleosidase followed by ATP-dependent MTR kinase (many bacteria, plants). MTR-1-P isomerase converts MTR-1-P to the ribulose phosphate, which MTRu-1-P dehydratase converts to the 2,3-diketo phosphate. An enolase and a phosphatase then form the acireductone 1,2-dihydroxy-5-(methylthio)pent-1-en-3-one. Fungi and animals do this with one bifunctional enolase-phosphatase (E1); Bacillus uses a RuBisCO-like enolase (MtnW) and a separate phosphatase (MtnX). An Fe(II)-dependent acireductone dioxygenase then oxidises the acireductone to 4-methylthio-2-oxobutanoate (KMTB) and formate. A final transamination converts KMTB to methionine. This step is redundant and is carried out by broad-specificity aromatic and branched-chain amino acid transaminases, not a dedicated enzyme. The cycle needs dioxygen and is largely cytosolic.

MODULE:methionine_salvage_mta_cycleDRAFTMetabolic Pathwaymodules/methionine_salvage_mta_cycle.yaml
L-methionine salvageGO:0071267
YeastPathways:PWY3O-64
methionine salvage pathway
Source pathway for the S. cerevisiae realisation (six reactions). The SGD summary pathway lists MEU1, MRI1, MDE1, UTR4 and ADI1 for the five dedicated steps and ARO8, ARO9, BAT1 and BAT2 for the final transamination (EC 2.6.1.88). All nine assignments were retained. The YeastCyc reaction records cite literature for every step except the MTA phosphorylase reaction; MEU1 is supported here by PMID:16530730 and PMID:18625006.
YeastPathways:PWY3O-351
superpathway of methionine salvage pathway
Superpathway that adds methionine adenosyltransferase (SAM1/SAM2), SAM decarboxylase (SPE2), spermidine synthase (SPE3) and spermine synthase (SPE4) as the MTA-producing reactions. These belong to the methionine_cycle and polyamine_metabolism modules and are outside this module's boundary, which begins with MTA.
GO:0071267
L-methionine salvage
Module-level process. GO:0071267 L-methionine salvage is the most specific live process term for the MTA cycle; the MTA-specific GO:0019509 is obsolete in QuickGO and GO:0033353 L-methionine cycle explicitly denotes the SAM/SAH/homocysteine cycle, not the MTA cycle.
GO:0019509
obsolete L-methionine salvage from methylthioadenosine
QuickGO marks the former MTA-specific L-methionine salvage from methylthioadenosine term obsolete because it represents a specific pathway beyond GO's intended specificity.
PMID:18625006
A complete inventory of all enzymes in the eukaryotic methionine salvage pathway.
Identifies and verifies all S. cerevisiae MTA-cycle enzymes (Meu1p, Mri1p, Mde1p, Utr4p, Adi1p) and shows that the final transamination is redundant and is mainly carried out by Aro8p, Aro9p, Bat1p and Bat2p.
The genes encoding 5'-methylthioribose-1-phosphate isomerase and 5'-methylthioribulose-1-phosphate dehydratase are herein named MRI1 and MDE1, respectively.
PMID:19946895
Metabolic characteristics and importance of the universal methionine salvage pathway recycling methionine from 5'-methylthioadenosine.
Review of the pathway, its two entry routes and its lineage variation.
MTA is first converted to 5'-methylthioribose-1-phosphate either by MTA phosphorylase or the combined action of MTA nucleosidase and 5'-methylthioribose kinase.
PMID:16530730
Methylthioadenosine and polyamine biosynthesis in a Saccharomyces cerevisiae meu1delta mutant.
meu1 deletion abolishes MTA phosphorylase-dependent MTA turnover; >98% of yeast MTA comes from polyamine synthesis.
we showed that >98% of methylthioadenosine is produced as a byproduct of polyamine synthesis
PMID:15215245
Crystal structure of yeast Ypr118w, a methylthioribose-1-phosphate isomerase related to regulatory eIF2B subunits.
Ypr118w (Mri1) is an eIF2B-related MTR-1-P isomerase required for growth on MTA.
In vivo, Ypr118w protein is required for yeast cells to grow on methylthioadenosine in the absence of methionine
PMID:15938715
Membrane-type 1 matrix metalloproteinase cytoplasmic tail binding protein-1 (MTCBP-1) acts as an eukaryotic aci-reductone dioxygenase (ARD) in the methionine salvage pathway.
Yeast YMR009w (ADI1) and human MTCBP-1 (ADI1) act as acireductone dioxygenase in the MTA cycle.
Disruption of the yeast ARD homolog, YMR009w gene, abolished ability of the cells to grow in this culture condition.
PMID:15102328
Bacterial variations on the methionine salvage pathway.
Describes the bacterial variants: nucleosidase plus kinase entry, and a split enolase (RuBisCO-like MtnW) plus phosphatase (MtnX) in B. subtilis versus a bifunctional enolase-phosphatase in other organisms.
While in B. subtilis this is performed by two distinct polypeptides, in the other organisms analyzed here an enolase-phosphatase yields 1,2-dihydroxy-3-keto-5-methylthiopentene.
15Nodes
10Parts
2Variant Sets
4Variants
10Annotons
7Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:methionine_salvage_mta_cycle 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.

  • mtr1p_formation_step → mtr1p_isomerase_step [NOT_CHECKED]
    Both entry routes yield MTR-1-P, the isomerase substrate.
  • mtr1p_isomerase_step → mtru1p_dehydratase_step [NOT_CHECKED]
    MTRu-1-P is the isomerase product and dehydratase substrate.
  • mtru1p_dehydratase_step → acireductone_formation_step [NOT_CHECKED]
    2,3-diketo-5-methylthiopentyl 1-phosphate is the dehydratase product and the enolase(-phosphatase) substrate.
  • acireductone_formation_step → acireductone_dioxygenase_step [NOT_CHECKED]
    The acireductone is the dioxygenase substrate.
  • acireductone_dioxygenase_step → kmtb_transamination_step [NOT_CHECKED]
    KMTB is the dioxygenase product and the transaminase substrate.

Function consistency and core coverage

11 gene-function check(s) reflected in core functions · 0 conflict(s) · 18 evidence or coverage gap(s) (38 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
mta_phosphorylase_activity MEU1 (S. cerevisiae)
UniProtKB:Q07938
Family Representative 		S-methyl-5-thioadenosine phosphorylase activity
GO:0017061 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mta_phosphorylase_activity mta1 (S. pombe, SPAC16C9.02c)
UniProtKB:Q09816
Family Representative 		S-methyl-5-thioadenosine phosphorylase activity
GO:0017061 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mta_phosphorylase_activity MTAP (human)
UniProtKB:Q13126
Family Representative 		S-methyl-5-thioadenosine phosphorylase activity
GO:0017061 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
mta_nucleosidase_activity mtnN (Bacillus subtilis 168)
UniProtKB:O32028
Family Representative 		methylthioadenosine nucleosidase activity
GO:0008930 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
mtr_kinase_activity mtnK (Bacillus subtilis 168)
UniProtKB:O31663
Family Representative 		S-methyl-5-thioribose kinase activity
GO:0046522 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
mtr1p_isomerase_activity MRI1 (S. cerevisiae)
UniProtKB:Q06489
Family Representative 		S-methyl-5-thioribose-1-phosphate isomerase activity
GO:0046523 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mtr1p_isomerase_activity mri1 (S. pombe)
UniProtKB:O60185
Family Representative 		S-methyl-5-thioribose-1-phosphate isomerase activity
GO:0046523 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mtr1p_isomerase_activity MRI1 (human)
UniProtKB:Q9BV20
Family Representative 		S-methyl-5-thioribose-1-phosphate isomerase activity
GO:0046523 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
mtr1p_isomerase_activity mtnA (Bacillus subtilis 168)
UniProtKB:O31662
Family Representative 		S-methyl-5-thioribose-1-phosphate isomerase activity
GO:0046523 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
mtru1p_dehydratase_activity MDE1 (S. cerevisiae)
UniProtKB:P47095
Family Representative 		methylthioribulose 1-phosphate dehydratase activity
GO:0046570 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mtru1p_dehydratase_activity mde1 (S. pombe, SPAC20H4.05c)
UniProtKB:Q9HE08
Family Representative 		methylthioribulose 1-phosphate dehydratase activity
GO:0046570 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mtru1p_dehydratase_activity APIP (human)
UniProtKB:Q96GX9
Family Representative 		methylthioribulose 1-phosphate dehydratase activity
GO:0046570 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mtru1p_dehydratase_activity mtnB (Bacillus subtilis 168)
UniProtKB:O31668
Family Representative 		methylthioribulose 1-phosphate dehydratase activity
GO:0046570 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
enolase_phosphatase_e1_activity UTR4 (S. cerevisiae)
UniProtKB:P32626
Family Representative 		acireductone synthase activity
GO:0043874 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
enolase_phosphatase_e1_activity utr4 (S. pombe)
UniProtKB:Q9P6Q2
Family Representative 		acireductone synthase activity
GO:0043874 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
enolase_phosphatase_e1_activity ENOPH1 (human)
UniProtKB:Q9UHY7
Family Representative 		acireductone synthase activity
GO:0043874 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
rlp_enolase_activity mtnW (Bacillus subtilis 168)
UniProtKB:O31666
Family Representative 		2,3-diketo-5-methylthiopentyl-1-phosphate enolase activity
GO:0043715 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
hkmtp_phosphatase_activity mtnX (Bacillus subtilis 168)
UniProtKB:O31667
Family Representative 		2-hydroxy-3-keto-5-methylthiopentenyl-1-phosphate phosphatase activity
GO:0043716 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
acireductone_dioxygenase_activity ADI1 (S. cerevisiae)
UniProtKB:Q03677
Family Representative 		acireductone dioxygenase [iron(II)-requiring] activity
GO:0010309 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
acireductone_dioxygenase_activity adi1 (S. pombe)
UniProtKB:O94286
Family Representative 		acireductone dioxygenase [iron(II)-requiring] activity
GO:0010309 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
acireductone_dioxygenase_activity ADI1 / MTCBP-1 (human)
UniProtKB:Q9BV57
Family Representative 		acireductone dioxygenase [iron(II)-requiring] activity
GO:0010309 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
acireductone_dioxygenase_activity mtnD (Bacillus subtilis 168)
UniProtKB:O31669
Family Representative 		acireductone dioxygenase [iron(II)-requiring] activity
GO:0010309 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
kmtb_transaminase_activity ARO8 (S. cerevisiae)
UniProtKB:P53090
Family Representative 		L-methionine:oxo-acid transaminase activity
GO:0010326 		Annotation Supported
A retained annotation or curated replacement supports this function, but core_functions does not yet reflect it.
kmtb_transaminase_activity ARO9 (S. cerevisiae)
UniProtKB:P38840
Family Representative 		L-methionine:oxo-acid transaminase activity
GO:0010326 		Annotation Supported
A retained annotation or curated replacement supports this function, but core_functions does not yet reflect it.
kmtb_transaminase_activity BAT1 (S. cerevisiae)
UniProtKB:P38891
Family Representative 		L-methionine:oxo-acid transaminase activity
GO:0010326 		Non Core Supported
The review explicitly retains this function as non-core; promotion into core_functions is not implied.
kmtb_transaminase_activity BAT2 (S. cerevisiae)
UniProtKB:P47176
Family Representative 		L-methionine:oxo-acid transaminase activity
GO:0010326 		Non Core Supported
The review explicitly retains this function as non-core; promotion into core_functions is not implied.
kmtb_transaminase_activity mtnE (Bacillus subtilis 168)
UniProtKB:O31665
Family Representative 		L-methionine:oxo-acid transaminase activity
GO:0010326 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
mta_phosphorylase_activity MTA phosphorylase (MtnP/MTAP)
PANTHER:PTHR42679:SF2
Family 		S-methyl-5-thioadenosine phosphorylase activity
GO:0017061 		Family Supported
Family review supports GO:0017061 FAMILY_WIDE. Asserted by methionine_salvage_mta_cycle (SF2); accepted by MEU1 and SPAC16C9.02c.
mta_nucleosidase_activity MTA/SAH nucleosidase
PANTHER:PTHR46832:SF1
Family 		methylthioadenosine nucleosidase activity
GO:0008930 		Family Supported
Family review supports GO:0008930 for PANTHER:PTHR46832:SF1. Asserted by methionine_salvage_mta_cycle; accepted by E. coli pfs.
mtr_kinase_activity methylthioribose kinase
PANTHER:PTHR34273
Family 		S-methyl-5-thioribose kinase activity
GO:0046522 		Family Function Unreviewed
Family review leaves GO:0046522 UNRESOLVED. Asserted by methionine_salvage_mta_cycle for Bacillus MtnK. SF2 also contains PsiK, a 4-hydroxytryptamine kinase, so the activity cannot be scoped by subfamily. No member gene review exists.
mtr1p_isomerase_activity eIF2B-alpha/beta/delta-related MTR-1-P isomerase
PANTHER:PTHR43475:SF1
Family 		S-methyl-5-thioribose-1-phosphate isomerase activity
GO:0046523 		Family Supported
Family review supports GO:0046523 for PANTHER:PTHR43475:SF1. Asserted by methionine_salvage_mta_cycle; accepted by every reviewed member.
mtr1p_isomerase_activity eIF2B-alpha/beta/delta-related MTR-1-P isomerase
PANTHER:PTHR43475:SF4
Family 		S-methyl-5-thioribose-1-phosphate isomerase activity
GO:0046523 		Family Supported
Family review supports GO:0046523 for PANTHER:PTHR43475:SF4. Asserted by methionine_salvage_mta_cycle; accepted by every reviewed member.
mtru1p_dehydratase_activity class II aldolase-fold MTRu-1-P dehydratase
PANTHER:PTHR10640:SF7
Family 		methylthioribulose 1-phosphate dehydratase activity
GO:0046570 		Family Supported
Family review supports GO:0046570 for PANTHER:PTHR10640:SF7. SF7 only, as methionine_salvage_mta_cycle selects; accepted by MDE1, mde1 and APIP.
enolase_phosphatase_e1_activity HAD-superfamily enolase-phosphatase E1
PANTHER:PTHR20371:SF1
Family 		acireductone synthase activity
GO:0043874 		Family Supported
Family review supports GO:0043874 FAMILY_WIDE. Asserted by methionine_salvage_mta_cycle (SF1); accepted by UTR4, utr4 and poplar MTNB.
rlp_enolase_activity RuBisCO-like protein (RLP) enolase
Family 		2,3-diketo-5-methylthiopentyl-1-phosphate enolase activity
GO:0043715 		Family Id Missing
The family has no identifier linking it to a curated family review.
hkmtp_phosphatase_activity HAD-like MtnX phosphatase
Family 		2-hydroxy-3-keto-5-methylthiopentenyl-1-phosphate phosphatase activity
GO:0043716 		Family Id Missing
The family has no identifier linking it to a curated family review.
acireductone_dioxygenase_activity cupin acireductone dioxygenase
PANTHER:PTHR23418:SF0
Family 		acireductone dioxygenase [iron(II)-requiring] activity
GO:0010309 		Family Supported
Family review supports GO:0010309 for PANTHER:PTHR23418:SF0. Catalytic ARD subfamilies, as methionine_salvage_mta_cycle selects SF0; not the inactive nematode subfamilies.
kmtb_transaminase_activity aromatic (class I) and branched-chain (class IV) amino acid transaminases
Family 		L-methionine:oxo-acid transaminase activity
GO:0010326 		Family Id Missing
The family has no identifier linking it to a curated family review.

Gene-review completeness (15/27 grounded genes reviewed)

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

Gene Review Complete Deep research
adi1 O94286 ✓ ✓ ✗
ADI1 Q03677 ✓ 24/25 ✓
APIP Q96GX9 ✓ 35/37 ✓
ARO8 P53090 ✓ ✓ ✓
ARO9 P38840 ✓ ✓ ✓
BAT1 P38891 ✓ ✓ ✓
BAT2 P47176 ✓ ✓ ✓
MDE1 P47095 ✓ ✓ ✓
mde1 Q9HE08 ✓ ✓ ✗
MEU1 Q07938 ✓ 23/24 ✓
mri1 O60185 ✓ ✓ ✗
MRI1 Q06489 ✓ ✓ ✓
mtnA (Bacillus subtilis 168) O31662 ✗ — —
mtnK (Bacillus subtilis 168) O31663 ✗ — —
mtnE (Bacillus subtilis 168) O31665 ✗ — —
mtnW (Bacillus subtilis 168) O31666 ✗ — —
mtnX (Bacillus subtilis 168) O31667 ✗ — —
mtnB (Bacillus subtilis 168) O31668 ✗ — —
mtnD (Bacillus subtilis 168) O31669 ✗ — —
mtnN (Bacillus subtilis 168) O32028 ✗ — —
MTAP (human) Q13126 ✗ — —
MRI1 (human) Q9BV20 ✗ — —
ADI1 / MTCBP-1 (human) Q9BV57 ✗ — —
ENOPH1 (human) Q9UHY7 ✗ — —
SPAC16C9.02c Q09816 ✓ ✓ ✗
UTR4 P32626 ✓ ✓ ✓
utr4 Q9P6Q2 ✓ ✓ ✗

Details

Context
cytosolGO:0005829
Methionine salvage from 5'-methylthioadenosine (MTA cycle)Metabolic Pathwaymethionine_salvage_mta_cycle

MTA -> MTR-1-P -> MTRu-1-P -> 2,3-diketo-5-methylthiopentyl 1-phosphate -> acireductone -> 4-methylthio-2-oxobutanoate -> L-methionine.

L-methionine salvageGO:0071267
Context
cytosolGO:0005829

Boundary: begins with 5'-methylthioadenosine and ends with L-methionine. MTA-producing reactions (SAM decarboxylase SPE2, spermidine synthase SPE3, spermine synthase SPE4) and SAM synthesis (SAM1/SAM2), which the YeastPathways superpathway PWY3O-351 adds, belong to the polyamine_metabolism and methionine_cycle modules. MTA export and alternative MTA fates (e.g. 5-methylthioribose excretion in E. coli) are outside the module. YeastCyc corrections: none to gene assignments. The SGD summary lists all five dedicated enzymes (MEU1, MRI1, MDE1, UTR4, ADI1) plus ARO8, ARO9, BAT1, BAT2, consistent with Pirkov et al. 2008 (PMID:18625006), which also excluded the UTR4 homologue YNL010w. Compartment: the GO-CAMs place every step in the cytosol, but BAT1 is the mitochondrial branched-chain transaminase, so its contribution to KMTB transamination presumably occurs in the mitochondrial matrix (KMTB import not established); BAT2, ARO8 and ARO9 are cytosolic. GO-CAM disagreements: (1) the YeastPathways models type the R15-RXN transamination for all four transaminases with GO:0052656 L-isoleucine transaminase activity, which is a different reaction. The pathway step is GO:0010326 L-methionine:oxo-acid transaminase activity (EC 2.6.1.88), used here. (2) PomBase model gomodel:69c59f8a00000584 is titled with GO:0033353 L-methionine cycle, but its content is this MTA salvage cycle. GO:0033353 denotes the SAM/SAH/homocysteine cycle, and GO:0071267 L-methionine salvage is the nearest live branch term for MTA-cycle genes because QuickGO marks GO:0019509 obsolete. GO:0033353 annotations on MTA-cycle genes (e.g. UTR4, ADI1, MDE1, MRI1, MEU1) are cross-branch migrations to fix. (3) The PomBase model has two MTRu-1-P dehydratase activities, mde1 (SPAC20H4.05c, PTHR10640:SF7, the MDE1/APIP orthologue) and mta3 (SPAC9.06c, UniProt Q9UT22, "methylthioribulose-1-phosphate dehydratase-like protein", PTHR10640:SF10). mta3's enabled-by evidence in the model is IBA only (PTN000067541). Only mde1 is used as the S. pombe exemplar here, and whether mta3 is a second active dehydratase or a diverged paralogue is left open. (4) The PomBase model has no transamination step. Lineage variation: the dedicated dioxygenase step needs O2, and some bacteria (e.g. E. coli) lack a complete pathway (PMID:19946895). The nucleosidase/kinase entry and the split MtnW/MtnX enolase-phosphatase are bacterial/plant variants and have no yeast representatives. MTA phosphorylase also releases adenine to purine salvage.

Connections

Part 1: MTA to methylthioribose 1-phosphate (entry)
5'-methylthioadenosine to S-methyl-5-thio-alpha-D-ribose 1-phosphateReactionmtr1p_formation_step
Variant set: MTA entry routes by route variant (One Or More)
Direct phosphorolysis (MTA phosphorylase)Reactionmta_phosphorylase_route

Annotons

S-methyl-5'-thioadenosine phosphorylase
mta_phosphorylase_activity
Participant: Family: MTA phosphorylase (MtnP/MTAP)
Family:
MTA phosphorylase (MtnP/MTAP)PANTHER:PTHR42679:SF2
Representative Members: MEU1 (S. cerevisiae)UniProtKB:Q07938 mta1 (S. pombe, SPAC16C9.02c)UniProtKB:Q09816 MTAP (human)UniProtKB:Q13126
Required Function:
S-methyl-5-thioadenosine phosphorylase activityGO:0017061

Function

S-methyl-5-thioadenosine phosphorylase activityGO:0017061
Substrates: S-methyl-5'-thioadenosine phosphate
Products: S-methyl-5-thio-alpha-D-ribose 1-phosphate adenine

Locations

cytosolGO:0005829

Single-step, energy-sparing entry; also releases adenine for purine salvage.

Hydrolysis then phosphorylation (MTA nucleosidase + MTR kinase)Metabolic Pathwaymta_nucleosidase_kinase_route

Two-step entry found in many bacteria (e.g. Bacillus subtilis) and in plants: MTA is hydrolysed to 5-methylthioribose and adenine, and MTR is then phosphorylated by an ATP-dependent kinase. Not used by yeasts.

Connections

Part 1: MTA hydrolysis
5'-methylthioadenosine to 5-methylthioriboseReactionmta_nucleosidase_step

Annotons

MTA/SAH nucleosidase (MtnN)
mta_nucleosidase_activity
Participant: Family: MTA/SAH nucleosidase
Family:
MTA/SAH nucleosidase
Representative Members: mtnN (Bacillus subtilis 168)UniProtKB:O32028
Required Function:
methylthioadenosine nucleosidase activityGO:0008930

Function

methylthioadenosine nucleosidase activityGO:0008930
Substrates: S-methyl-5'-thioadenosine water
Products: S-methyl-5-thio-D-ribose adenine
Part 2: MTR phosphorylation
5-methylthioribose to S-methyl-5-thio-alpha-D-ribose 1-phosphateReactionmtr_kinase_step

Annotons

Methylthioribose kinase (MtnK)
mtr_kinase_activity
Participant: Family: methylthioribose kinase
Family:
methylthioribose kinasePANTHER:PTHR34273
Representative Members: mtnK (Bacillus subtilis 168)UniProtKB:O31663
Required Function:
S-methyl-5-thioribose kinase activityGO:0046522

Function

S-methyl-5-thioribose kinase activityGO:0046522
Substrates: S-methyl-5-thio-D-ribose ATP
Products: S-methyl-5-thio-alpha-D-ribose 1-phosphate ADP
Part 2: MTR-1-P isomerisation
MTR-1-P to S-methyl-5-thio-D-ribulose 1-phosphateReactionmtr1p_isomerase_step

Annotons

Methylthioribose-1-phosphate isomerase (MtnA/MRI1)
mtr1p_isomerase_activity
Participant: Family: eIF2B-alpha/beta/delta-related MTR-1-P isomerase
Family:
eIF2B-alpha/beta/delta-related MTR-1-P isomerase
Representative Members: MRI1 (S. cerevisiae)UniProtKB:Q06489 mri1 (S. pombe)UniProtKB:O60185 MRI1 (human)UniProtKB:Q9BV20 mtnA (Bacillus subtilis 168)UniProtKB:O31662
Required Function:
S-methyl-5-thioribose-1-phosphate isomerase activityGO:0046523

Function

S-methyl-5-thioribose-1-phosphate isomerase activityGO:0046523
Substrates: S-methyl-5-thio-alpha-D-ribose 1-phosphate
Products: S-methyl-5-thio-D-ribulose 1-phosphate

Locations

cytosolGO:0005829
Part 3: MTRu-1-P dehydration
MTRu-1-P to 5-(methylsulfanyl)-2,3-dioxopentyl 1-phosphateReactionmtru1p_dehydratase_step

Annotons

Methylthioribulose-1-phosphate dehydratase (MtnB/MDE1/APIP)
mtru1p_dehydratase_activity
Participant: Family: class II aldolase-fold MTRu-1-P dehydratase
Family:
class II aldolase-fold MTRu-1-P dehydratasePANTHER:PTHR10640:SF7
Representative Members: MDE1 (S. cerevisiae)UniProtKB:P47095 mde1 (S. pombe, SPAC20H4.05c)UniProtKB:Q9HE08 APIP (human)UniProtKB:Q96GX9 mtnB (Bacillus subtilis 168)UniProtKB:O31668
Required Function:
methylthioribulose 1-phosphate dehydratase activityGO:0046570

Function

methylthioribulose 1-phosphate dehydratase activityGO:0046570
Substrates: S-methyl-5-thio-D-ribulose 1-phosphate
Products: 5-(methylsulfanyl)-2,3-dioxopentyl 1-phosphate water

Locations

cytosolGO:0005829
Part 4: enolisation and dephosphorylation to acireductone
2,3-diketo-5-methylthiopentyl 1-phosphate to 1,2-dihydroxy-5-(methylthio)pent-1-en-3-oneReactionacireductone_formation_step
Variant set: Enolase-phosphatase architecture variants by enzyme architecture (Exactly One)
Bifunctional enolase-phosphatase E1 (fungi, animals, many bacteria)Reactionbifunctional_e1_variant

Annotons

Enolase-phosphatase E1 (acireductone synthase)
enolase_phosphatase_e1_activity
Participant: Family: HAD-superfamily enolase-phosphatase E1
Family:
HAD-superfamily enolase-phosphatase E1PANTHER:PTHR20371:SF1
Representative Members: UTR4 (S. cerevisiae)UniProtKB:P32626 utr4 (S. pombe)UniProtKB:Q9P6Q2 ENOPH1 (human)UniProtKB:Q9UHY7
Required Function:
acireductone synthase activityGO:0043874

Function

acireductone synthase activityGO:0043874
Substrates: 5-(methylsulfanyl)-2,3-dioxopentyl 1-phosphate water
Products: 1,2-dihydroxy-5-(methylsulfanyl)pent-1-en-3-one phosphate

Locations

cytosolGO:0005829
Separate RuBisCO-like enolase and phosphatase (Bacillus-type)Metabolic Pathwaysplit_enolase_phosphatase_variant

In Bacillus subtilis and some other Firmicutes the two half-reactions are carried out by a RuBisCO-like protein (MtnW) acting as enolase and by a separate phosphatase (MtnX) (PMID:15102328).

Connections

Part 1: enolisation
2,3-diketo-5-methylthiopentyl 1-phosphate to 2-hydroxy-3-keto-5-methylthiopentenyl 1-phosphateReactiondkmtp_enolase_step

Annotons

RuBisCO-like DK-MTP-1-P enolase (MtnW)
rlp_enolase_activity
Participant: Family: RuBisCO-like protein (RLP) enolase
Family:
RuBisCO-like protein (RLP) enolase
Representative Members: mtnW (Bacillus subtilis 168)UniProtKB:O31666
Required Function:
2,3-diketo-5-methylthiopentyl-1-phosphate enolase activityGO:0043715

Function

2,3-diketo-5-methylthiopentyl-1-phosphate enolase activityGO:0043715
Substrates: 5-(methylsulfanyl)-2,3-dioxopentyl 1-phosphate
Products: 2-hydroxy-5-(methylsulfanyl)-3-oxopent-1-enyl phosphate
Part 2: dephosphorylation
2-hydroxy-3-keto-5-methylthiopentenyl 1-phosphate to acireductoneReactionhkmtp_phosphatase_step

Annotons

HK-MTPenyl-1-P phosphatase (MtnX)
hkmtp_phosphatase_activity
Participant: Family: HAD-like MtnX phosphatase
Family:
HAD-like MtnX phosphatase
Representative Members: mtnX (Bacillus subtilis 168)UniProtKB:O31667
Required Function:
2-hydroxy-3-keto-5-methylthiopentenyl-1-phosphate phosphatase activityGO:0043716

Function

2-hydroxy-3-keto-5-methylthiopentenyl-1-phosphate phosphatase activityGO:0043716
Substrates: 2-hydroxy-5-(methylsulfanyl)-3-oxopent-1-enyl phosphate water
Products: 1,2-dihydroxy-5-(methylsulfanyl)pent-1-en-3-one phosphate
Part 5: acireductone oxidation
acireductone + O2 to 4-methylthio-2-oxobutanoate + formateReactionacireductone_dioxygenase_step

Annotons

Acireductone dioxygenase, Fe(II) form (MtnD/ADI1)
acireductone_dioxygenase_activity
Participant: Family: cupin acireductone dioxygenase
Family:
cupin acireductone dioxygenasePANTHER:PTHR23418:SF0
Representative Members: ADI1 (S. cerevisiae)UniProtKB:Q03677 adi1 (S. pombe)UniProtKB:O94286 ADI1 / MTCBP-1 (human)UniProtKB:Q9BV57 mtnD (Bacillus subtilis 168)UniProtKB:O31669
Required Function:
acireductone dioxygenase [iron(II)-requiring] activityGO:0010309

Function

acireductone dioxygenase [iron(II)-requiring] activityGO:0010309
Substrates: 1,2-dihydroxy-5-(methylsulfanyl)pent-1-en-3-one dioxygen
Products: 4-methylsulfanyl-2-oxobutanoate formate

Locations

cytosolGO:0005829

The Fe(II)-bound enzyme makes the methionine precursor KMTB. The same proteins bound to Ni(II) make 3-methylthiopropanoate, CO and formate instead (GO:0010308), an off-pathway shunt not modelled as a step.

Part 6: final transamination (redundant)
4-methylthio-2-oxobutanoate to L-methionineReactionkmtb_transamination_step

Carried out by broad-specificity transaminases borrowed from amino acid metabolism; several unrelated aminotransferase folds contribute, so no single family is asserted.

Annotons

KMTB (methionine:2-oxo acid) transaminase
kmtb_transaminase_activity
Participant: Family: aromatic (class I) and branched-chain (class IV) amino acid transaminases
Family:
aromatic (class I) and branched-chain (class IV) amino acid transaminases Fold-type I aromatic transaminases (yeast Aro8/Aro9) and fold-type IV branched-chain transaminases (Bat1/Bat2) both contribute in yeast (PMID:18625006); B. subtilis uses the glutamine transaminase MtnE. These are in different PANTHER families, so no family id is asserted.
Representative Members: ARO8 (S. cerevisiae)UniProtKB:P53090 ARO9 (S. cerevisiae)UniProtKB:P38840 BAT1 (S. cerevisiae)UniProtKB:P38891 BAT2 (S. cerevisiae)UniProtKB:P47176 mtnE (Bacillus subtilis 168)UniProtKB:O31665
Required Function:
L-methionine:oxo-acid transaminase activityGO:0010326

Function

L-methionine:oxo-acid transaminase activityGO:0010326
Substrates: 4-methylsulfanyl-2-oxobutanoate L-alpha-amino acid (aromatic, branched-chain, glutamine and others)
Products: L-methionine 2-oxo carboxylate

Locations

cytosolGO:0005829