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# Glutamate is a single transamination reaction from 2-oxoglutarate # (alpha-ketoglutarate), which is an intermediate in the TCA # cycle. Amino acid transaminases are often non-specific, so glutamate # catabolism could be considered trivial. However, many amino acid # transaminases are 2-oxoglutarate dependent, so they cannot # contribute to glutamate catabolism. And even if the amino group is # transfered elsewhere, the ammonium group still needs to be # liberated somehow. GapMind represents glutamate degradation # using MetaCyc pathways # L-glutamate degradation I (glutamate dehydrogenase, metacyc:GLUTAMATE-DEG1-PWY), # pathway II via aspartate ammonia-lyase (metacyc:GLUTDEG-PWY), # and pathway VI via glutamate mutase (metacyc:PWY-5087). # Several other MetaCyc pathways are not included in GapMind. # Pathway IV (via gamma-aminobutanoate, metacyc:PWY-4321) is not thought to occur in prokaryotes. # Pathways V (via hydroxyglutarate, metacyc:P162-PWY) and XI (reductive Stickland reaction, metacyc:PWY-8190) # combine glutamate dehydrogenase with reductive pathways; # these are omitted because glutamate dehydrogenase alone # suffices for catabolism under respiratory conditions. # Pathways VII (to butanoate, metacyc:GLUDEG-II-PWY) and VIII (to propanoate, metacyc:PWY-5088) # are similar to pathway VI but also describe the fermentation of the pyruvate. # Pathway IX (via 4-aminobutanoate, metacyc:PWY0-1305) does not yield net consumption of glutamate: # the catabolism of 4-aminobutanoate relies on a transamination reaction that converts 2-oxoglutarate # to glutamate. # Most ABC transporters for glutamate have a substrate-binding component (gltI), # 2 transmembrane components (gltJ and gltK), and an ATPase component (gltL) # A very-similar system from Pseudomonas fluorescens GW456-L13 (PfGW456L13_4770:4773) was not found to be important # for glutamate utilization, and is ignored. gltI L-glutamate ABC transporter, substrate-binding component (GltI/AatJ) curated:CharProtDB::CH_002441 curated:TCDB::Q88NY2 curated:reanno::pseudo1_N1B4:Pf1N1B4_771 curated:reanno::pseudo3_N2E3:AO353_16290 curated:TCDB::Q9I402 ignore:reanno::pseudo13_GW456_L13:PfGW456L13_4770 gltJ L-glutamate ABC transporter, permease component 1 (gltJ/aatQ) curated:SwissProt::P0AER3 curated:TCDB::Q88NY3 curated:reanno::pseudo1_N1B4:Pf1N1B4_772 curated:reanno::pseudo3_N2E3:AO353_16285 curated:TCDB::Q9I403 ignore:reanno::pseudo13_GW456_L13:PfGW456L13_4771 gltK L-glutamate ABC transporter, permease component 1 (gltK/aatM) curated:SwissProt::P0AER5 curated:TCDB::Q88NY4 curated:reanno::pseudo1_N1B4:Pf1N1B4_773 curated:reanno::pseudo3_N2E3:AO353_16280 curated:TCDB::Q9I404 ignore:reanno::pseudo13_GW456_L13:PfGW456L13_4772 # SMc02121 is quite similar and is the ATPase component of a putative amino acid transporter, so it is ignored. # Similarly for Q52815 gltL L-glutamate ABC transporter, ATPase component (GltL/GluA/BztD/GlnQ/AatP/PEB1C) curated:TCDB::A3ZI83 curated:TCDB::P0AAG3 curated:TCDB::P48243 curated:TCDB::Q52666 curated:TCDB::Q88NY5 curated:TCDB::Q9CES4 curated:reanno::pseudo1_N1B4:Pf1N1B4_774 curated:reanno::pseudo3_N2E3:AO353_16275 curated:TCDB::Q9I405 ignore:reanno::pseudo13_GW456_L13:PfGW456L13_4773 ignore:reanno::Smeli:SMc02121 ignore:TCDB::Q52815 # Transporters were identified using # query: transporter:glutamate:L-glutamate:glu glutamate-transport: gltI gltJ gltK gltL # In Corynebacterium glutamicum, the ABC transporter is known as gluABCD. # gluA is the ATPase component and is similar to gltL. # gluB is the substrate-binding component and gluC/gluD are membrane components. gluB L-glutamate ABC transporter, substrate-binding component GluB curated:TCDB::P48242 gluC L-glutamate ABC transporter, permease component 1 (GluC) curated:TCDB::P48244 gluD L-glutamate ABC transporter, permease component 2 (GluD) curated:TCDB::P48245 glutamate-transport: gltL gluB gluC gluD # In Rhodobacter capsulatus, the ABC transporter is known as bztABCD. # BztD is the ATPase component and is similar to gltL bztA L-glutamate ABC transporter, substrate-binding component curated:TCDB::Q52663 bztB L-glutamate ABC transporter, permease component 1 (BztB) curated:CharProtDB::CH_011913 bztC L-glutamate ABC transporter, permease component 2 (BztC) curated:TCDB::Q52665 glutamate-transport: bztA bztB bztC gltL # In Rhizobium leguminosarum, a broad-specificity amino acid ABC transporter is known as braCDEFG. # (A homologous system from Pseudomonas is thought to have a narrower substrate range.) braC ABC transporter for glutamate, histidine, arginine, and other amino acids, substrate-binding component BraC curated:TCDB::Q9L3M3 braD ABC transporter for glutamate, histidine, arginine, and other amino acids, permease component 1 (BraD) uniprot:Q1MCU0 braE ABC transporter for glutamate, histidine, arginine, and other amino acids, permease component 2 (BraE) uniprot:Q1MCU1 braF ABC transporter for glutamate, histidine, arginine, and other amino acids, ATPase component 1 (BraF) uniprot:Q1MCU2 braG ABC transporter for glutamate, histidine, arginine, and other amino acids, ATPase component 2 (BraG) uniprot:Q1MCU3 glutamate-transport: braC braD braE braF braG # GlnQP from Lactococcus lactis, TC 3.A.1.3.25, has just two components: # glnP has fused permease and substrate-binding domains, and glnQ is similar to gltL glnP L-glutamate ABC transporter, fused permease and substrate-binding components GlnP curated:TCDB::Q9CES5 glutamate-transport: gltL glnP # Campylobacter has an ABC transporter with just 1 permease component (Peb1ABC). # The ATPase component (peb1C) clusters with gltL peb1A L-glutamate ABC transporter, substrate-binding component Peb1A curated:CharProtDB::CH_021449 peb1B L-glutamate ABC transporter, permease component Peb1B curated:TCDB::A1VZQ3 glutamate-transport: peb1A peb1B gltL # Synechocystis sp. PCC 6803 has a tripartite (DctMQP-like) glutamate transporter gtrA tripartite L-glutamate:Na+ symporter, small membrane component GtrA curated:TCDB::P74225 gtrB tripartite L-glutamate:Na+ symporter, large membrane component GtrB curated:TCDB::P74224 gtrC tripartite L-glutamate:Na+ symporter, substrate-binding component GtrC curated:TCDB::P74223 glutamate-transport: gtrA gtrB gtrC # aapJQMP from Rhizobium leguminosarum (a very similar system from S. meliloti is ignored) aapJ ABC transporter for amino acids (Asp/Asn/Glu/Pro/Leu), substrate-binding component AapJ curated:TCDB::Q52812 ignore:reanno::Smeli:SMc02118 aapQ ABC transporter for amino acids (Asp/Asn/Glu/Pro/Leu), permease component 1 (AapQ) curated:TCDB::Q52813 ignore:reanno::Smeli:SMc02119 aapM ABC transporter for amino acids (Asp/Asn/Glu/Pro/Leu), permease component 2 (AapM) curated:TCDB::Q52814 ignore:reanno::Smeli:SMc02120 aapP ABC transporter for amino acids (Asp/Asn/Glu/Pro/Leu), ATPase component AapP curated:TCDB::Q52815 ignore:reanno::Smeli:SMc02121 glutamate-transport: aapJ aapQ aapM aapP # Homomeric transporters gltS L-glutamate:Na+ symporter GltS curated:SwissProt::P0AER8 curated:TCDB::P73275 curated:TCDB::Q9HZ58 glutamate-transport: gltS acaP L-glutamate permease AcaP curated:SwissProt::A2RL65 curated:TCDB::F2HJG8 ignore:TCDB::P75835 glutamate-transport: acaP # Fitness data from Shewanella amazonensis identified a similar protein, # Sama_1319 (A1S570), as the glutamate transporter. # It is also related to the aspartate transporter Glt(Ph) (O59010), which has little glutamate transport # and is marked ignore. # Also identified Psest_4075 (L0GT47) gltP L-glutamate:cation symporter GltP/GltT curated:SwissProt::P21345 curated:SwissProt::P39817 curated:CharProtDB::CH_088342 curated:SwissProt::P24943 uniprot:A1S570 uniprot:L0GT47 ignore:SwissProt::O59010 glutamate-transport: gltP yveA L-glutamate:H+ symporter YveA curated:SwissProt::O07002 glutamate-transport: yveA gltS_Syn L-glutamate:Na+ symporter GltS_Syn curated:TCDB::B1XKD9 glutamate-transport: gltS_Syn dmeA L-glutamate transporter DmeA curated:TCDB::Q31PG5 glutamate-transport: dmeA # Ignored excitatory glutamate transporters from animals. # Ignored Glt(Ph) (O59010), reported to have very low activity with glutamate as # the substrate (see SwissProt page) # Ignored eukaryotic vesicular transporters # Ignored solute carrier family proteins from animals # Ignored mitochondrial glutamate carriers # Ignored glutamate:GABA antiporters (GadC) # Ignored chloroplast glutamate/malate translocators # Ignored the yeast SAM transporter # Ignored the animal glutamate exporter polyphemus # Ignored vcINDY (Q9KNE0), which is a dicarboxylate transporter and might be a glutamate transporter # The NADP dependent enzyme acts primarily in the reverse direction, # so would not contribute to catabolism. # EC 1.4.1.3 describes glutamate dehydrogenases that can use either # NAD or NADP; these are ignored. # AZOBR_RS00190 (G8AE86) is important for proline and glutamine catabolism, and # both are catabolized via glutamate; this confirms it is a glutamate dehydrogenase. gdhA glutamate dehydrogenase, NAD-dependent EC:1.4.1.2 uniprot:G8AE86 ignore_other:1.4.1.3 # GdhA is glutamate dehydrogenase (forming 2-oxoglutarate and ammonia). all: glutamate-transport gdhA aspA L-aspartate ammonia-lyase EC:4.3.1.1 # In pathway II, glutamate and oxaloacetate are transaminated to 2-oxoglutarate and aspartate, # and the aspartate is cleaved to fumarate and ammonium by aspA. # (The transamination reaction is not represented. Both oxaloacetate and fumarate are TCA cycle intermediates.) all: glutamate-transport aspA glmS L-glutamate mutase, S component curated:SwissProt::P80078 curated:SwissProt::Q05488 curated:metacyc::MONOMER-16253 glmE L-glutamate mutase, E component curated:SwissProt::P80077 curated:SwissProt::Q05509 curated:metacyc::MONOMER-16254 mal methylaspartate ammonia-lyase EC:4.3.1.2 # An enzyme from Burkholderia xenovorans was shown to have a physiologically relevant # mesaconase. Many fumarases (EC 4.2.1.2) may have this activity # as well, so they are marked ignore. fumD (S)-2-methylmalate dehydratase (mesaconase) EC:4.2.1.34 ignore_other:4.2.1.2 # Although the citramalate lyase is described as a single reaction in # MetaCyc, the enzyme database entry (EC:4.1.3.22) suggests that it is # a two-step reaction: citramalate CoA-transferase (EC:2.8.3.11) and # citramalyl-CoA lyase (EC:4.1.3.25). No citramalate CoA-transferase # proteins have been linked to sequence, but citramalyl-CoA lyases are # known, so only this step is included. # Some (S-citramalyl-CoA lyases are very similar to malyl-CoA lyases, which are marked ignore. mcl (S)-citramalyl-CoA pyruvate-lyase EC:4.1.3.25 ignore:reanno::Phaeo:GFF3000 ignore:SwissProt::B6E2X2 # In pathway VI, the mutase glmSE converts glutamate to (2S,3S)-3-methylaspartate, # the lyase mal forms 2-methylfumarate (mesaconate), # the hydratase fumD forms (S)-2-methylmalate (citramalate), # and a lyase forms acetate and pyruvate. all: glutamate-transport glmS glmE mal fumD mcl
Each pathway is defined by a set of rules based on individual steps or genes. Candidates for each step are identified by using ublast (a fast alternative to protein BLAST) against a database of manually-curated proteins (most of which are experimentally characterized) or by using HMMer with enzyme models (usually from TIGRFam). Ublast hits may be split across two different proteins.
A candidate for a step is "high confidence" if either:
Otherwise, a candidate is "medium confidence" if either:
Other blast hits with at least 50% coverage are "low confidence."
Steps with no high- or medium-confidence candidates may be considered "gaps." For the typical bacterium that can make all 20 amino acids, there are 1-2 gaps in amino acid biosynthesis pathways. For diverse bacteria and archaea that can utilize a carbon source, there is a complete high-confidence catabolic pathway (including a transporter) just 38% of the time, and there is a complete medium-confidence pathway 63% of the time. Gaps may be due to:
GapMind relies on the predicted proteins in the genome and does not search the six-frame translation. In most cases, you can search the six-frame translation by clicking on links to Curated BLAST for each step definition (in the per-step page).
For more information, see:
If you notice any errors or omissions in the step descriptions, or any questionable results, please let us know
by Morgan Price, Arkin group, Lawrence Berkeley National Laboratory