Definition of pyruvate catabolism

As rules and steps, or see full text

Rules

Overview: Pyruvate is a central metabolite, so GapMind represents transport only.

• all: pyruvate-transport
• pyruvate-transport:
  • yjcH and actP
  • or cstA and ybdD
  • or SLC5A8
  • or dctM, dctP and dctQ
  • or JEN1
  • or btsT
  • or mctC
  • or MCT4
  • or mctP
  • Comment: Most of these transporters were identified using curated clusters and query: transporter:pyruvate. ActP-yjcH and cstA-ybdD were identified from mutant fitness data.

Steps

actP: large subunit of pyruvate transporter (actP-like)

• UniProt sequence A0A1N7U9G2: SubName: Full=Acetate permease {ECO:0000313|EMBL:AIB35691.1}; SubName: Full=Actetate permease {ECO:0000313|EMBL:ERH55332.1}; SubName: Full=Cation acetate symporter {ECO:0000313|EMBL:PRW83281.1}; SubName: Full=Cation/acetate symporter {ECO:0000313|EMBL:SFB56078.1};
• UniProt sequence G8AHY6: SubName: Full=Acetate transporter {ECO:0000313|EMBL:CCC96889.1};
• UniProt sequence A0A166PH03: SubName: Full=Cation acetate symporter {ECO:0000313|EMBL:KZN18898.1};
• UniProt sequence A0A165ZRB0: SubName: Full=Cation acetate symporter {ECO:0000313|EMBL:AMZ74981.1};
• Ignore hits to P32705 when looking for 'other' hits (Cation/acetate symporter ActP; Acetate permease; Acetate transporter ActP. Acetate/glyoxylate permease, ActP. acetate/glycolate:cation symporter. acetate/glycolate:cation symporter)
• UniProt sequence E4PHQ0: SubName: Full=Sodium: solute symporter family protein {ECO:0000313|EMBL:ADP97015.1};
• Curated sequence GFF346: actP-like component of D-alanine uptake system
• Comment: A group of heterodimeric pyruvate transporters. This is the actP-like large subunit. WCS417:GFF1743 = A0A1N7U9G2, azobra:AZOBR_RS02940 = G8AHY6, pseudo1_N1B4:Pf1N1B4_3673 = A0A166PH03, pseudo6_N2E2:Pf6N2E2_5849 = A0A165ZRB0, and psRCH2:Psest_0347 (GFF346) Closely related to E. coli actP = P32705, so ignore that. Added Marinobacter HP15_1251 (E4PHQ0) because it has a specific phenotype (if mild) and fills the gap. And it is closely related to the D-alanine uptake system , so ignore that.
• Total: 6 characterized proteins

yjcH: putative small subunit of pyruvate transporter (yjcH-like)

• Curated sequence GFF1742: required for pyruvate transport, with PS417_08865 (actP-like)
• Curated sequence AZOBR_RS02935: required for pyruvate transport, with AZOBR_RS02940
• Curated sequence Pf1N1B4_3672: required for pyruvate transport, with Pf1N1B4_3673 (actP-like)
• Curated sequence Pf6N2E2_5848: required for pyruvate transport, with Pf6N2E2_5849 (actP-like)
• Ignore hits to 18096 when looking for 'other' hits (DUF485 domain-containing inner membrane protein YjcH. required for glycolate transport, with actP)
• UniProt sequence E4PHQ1: SubName: Full=Membrane protein containing probable solute: sodium symporter, small subunit domain {ECO:0000313|EMBL:ADP97016.1};
• Curated sequence GFF345: small component of D-alanine uptake system, with Psest_0347 (actP-like)
• Comment: This is the yjcH-like small subunit. These are similar to E. coli b4068/yjcH/18096, involved in glycolate & acetate transport, so ignore that. Added Marinobacter HP15_1252 (E4PHQ1) because it has a specific phenotype (if mild) and fills the gap.
• Total: 6 characterized proteins

cstA: large subunit of pyruvate transporter (CstA)

• UniProt sequence A0A0C4Y7X7: SubName: Full=Carbon starvation protein A {ECO:0000313|EMBL:AJG21527.1};
• Curated sequence P15078: Peptide transporter CstA; Carbon starvation protein A. carbon starvation protein A
• Curated sequence P39396: Pyruvate/proton symporter BtsT; Brenztraubensaure transporter; Pyruvate/H(+) symporter. pyruvate:H⁺ symporter. pyruvate:H⁺ symporter
• UniProt sequence A0A0N9VZ52: SubName: Full=Carbon starvation protein A {ECO:0000313|EMBL:ALI04206.1};
• Ignore hits to Q0P9Y2 when looking for 'other' hits (Peptide transporter CstA; Carbon starvation protein A. CstA of 703 aas and 18 putative TMSs. In C. jejuni, this protein plays a role in starvation responses and peptide uptake.  A ΔcstA mutant has reduced use of di- and tri-peptides when used as nitrogen sources. The mutant also has reduced motility and agglutination and shows decreased host-pathogen relationships)
• Comment: E. coli cstA (P15078) was originally thought to be a peptide transporter, but is involved in pyruvate transport along with ybdD (PMID:29358499). The related protein btsT (P39396, formerly yjiY) is also a pyruvate transporter. And a similar protein from Cupriavidus basilensis, RR42_RS20515 = A0A0C4Y7X7, is important for pyruvate utilization. As is AO353_25255 (A0A0N9VZ52) from Pseudomonas fluorescens FW300-N2E3. CstA and RR42_RS20515 seem to operate together with ybdD or similar proteins, but purified BtsT is reported to transport pyruvate (PMID:29061664), so it may not require a ybdD-like component. It is not clear if AO353_25255 functions with a ybdD-like component: the downstream gene, AO353_25260, is ybdD-like and has subtle defects during growth on pyruvate. Q0P9Y2 (CSTA_CAMJE) was proposed to be a peptide transporter in Campylobacter jejuni, but is suspiciously similar to pyruvate transporters, so is ignored.
• Total: 4 characterized proteins

ybdD: small subunit of pyruvate transporter (YbdD)

• UniProt sequence P0AAS9: RecName: Full=Uncharacterized protein YbdD;
• Curated sequence RR42_RS20510: required for pyruvate transport, with cstA-like RR42_RS20515
• Comment: E. coli ybdD (P0AAS9) is involved in pyruvate transport with cstA (PMID:29358499). And a similar protein from Cupriavidus basilensis, RR42_RS20510, is important for pyruvate utilization.
• Total: 2 characterized proteins

SLC5A8: sodium-coupled pyruvate transporter

• Curated sequence Q3ZMH1: Sodium-coupled monocarboxylate transporter 1; Electrogenic sodium monocarboxylate cotransporter; zSMCTe; Sodium solute symporter family 5 member 8 protein; Solute carrier family 5 member 8. sodium-coupled monocarboxylate transporter 1. The high affinity (Km (lactate) = 0.2mM) electrogenic Na+ monocarboxylate (lactate, pyruvate, butyrate, nicotinate) transporter, SMCTe
• Curated sequence Q7T384: Sodium-coupled monocarboxylate transporter 2; Electroneutral sodium monocarboxylate cotransporter; zSMCTn; Low-affinity sodium-lactate cotransporter; Solute carrier family 5 member 12; zSLC5A12. sodium-coupled monocarboxylate transporter 2. The low affinity (Km (lactate) = 2mM) electroneutral Na+:monocarboxylate (lactate, pyruvate, butyrate, nicotinate) transporter, SMCTn
• Curated sequence Q8N695: Sodium-coupled monocarboxylate transporter 1; Apical iodide transporter; Electrogenic sodium monocarboxylate cotransporter; Sodium iodide-related cotransporter; Solute carrier family 5 member 8. Na+-dependent short chain fatty acid transporter SLC5A8 (tumor suppressor gene product, down-regulated in colon cancer) (substrates: lactate, pyruvate, acetate, propionate, butyrate (Km ≈1 mM)) [propionate:Na+ = 1:3] (Miyauchi et al., 2004). Pyroglutamate (5-oxoproline) is also transported in a Na+- coupled mechanism (Miyauchi et al., 2010). SMCT1 and SMCT2 may transport monocarboxylate drugs (e.g. nicotinate and its derivatives) across the intestinal brush boarder membrane
• Total: 3 characterized proteins

dctP: pyruvate TRAP transporter, substrate-binding component

• Curated sequence Q8YSQ6: Monocarboxylate 2-oxoacid-binding periplasmic protein all3028; Extracellular solute-binding protein; Extracytoplasmic solute receptor protein all3028; TRAP transporter monocarboxylate 2-oxoacid-binding subunit P. Extracellular solute-binding protein, component of The 2-oxo monocarboxylate transporter (Pernil et al., 2010). Transports pyruvate which is inhibited by various 2-ketoacids
• Curated sequence D5ALT6: TRAP dicarboxylate transporter, DctP-2 subunit, component of The 2-ketomonocarboxylate transporter (presented in order of affinity - 2-oxovalerate [highest affinity, KD=0.1 μM], 2-oxoisovalerate, 2-oxobutyrate, 2-oxoisocaproate, 2-oxo-3-methylvalerate, pyruvate [lowest affinity, KD=3 μM])
• Ignore hits to Q3J1R2 when looking for 'other' hits (Alpha-keto acid-binding periplasmic protein TakP; Extracytoplasmic solute receptor protein TakP; TRAP transporter alpha-keto acid-binding subunit P; TRAP-T family sorbitol/mannitol transporter, periplasmic binding protein, SmoM)
• UniProt sequence Q48AL6: SubName: Full=Extracellular solute-binding protein, family 7 {ECO:0000313|EMBL:AAZ28655.1};
• Comment: DctP from Nostoc, Rhodobacter; associated with dctQ and dctM. Similar to TakP (Q3J1R2), which is misannotated and not characterized. The related protein Q48AL6 = CPS_0129 was shown to bind calcium-pyruvate (PMC4310620).
• Total: 3 characterized proteins

dctQ: pyruvate TRAP transporter, small permease component

• Curated sequence D5ATK0: Tripartite ATP-independent periplasmic transporter, DctQ-2 component, component of The 2-ketomonocarboxylate transporter (presented in order of affinity - 2-oxovalerate [highest affinity, KD=0.1 μM], 2-oxoisovalerate, 2-oxobutyrate, 2-oxoisocaproate, 2-oxo-3-methylvalerate, pyruvate [lowest affinity, KD=3 μM])
• Curated sequence Q8YSQ8: Alr3026 protein, component of The 2-oxo monocarboxylate transporter (Pernil et al., 2010). Transports pyruvate which is inhibited by various 2-ketoacids
• Total: 2 characterized proteins

dctM: pyruvate TRAP transporter, large permease component

• Curated sequence D5ATK1: TRAP C4-dicarboxylate transport system permease, DctM-2 subunit, component of The 2-ketomonocarboxylate transporter (presented in order of affinity - 2-oxovalerate [highest affinity, KD=0.1 μM], 2-oxoisovalerate, 2-oxobutyrate, 2-oxoisocaproate, 2-oxo-3-methylvalerate, pyruvate [lowest affinity, KD=3 μM])
• Curated sequence Q8YSQ7: Alr3027 protein, component of The 2-oxo monocarboxylate transporter (Pernil et al., 2010). Transports pyruvate which is inhibited by various 2-ketoacids
• Total: 2 characterized proteins

JEN1: pyruvate symporter JEN1

• Curated sequence CH_091331: Carboxylic acid transporter protein homolog. The lactate/pyruvate:H+ symporter. Residues in the substrate translocation pathway have been reported (Soares-Silva et al., 2011). This systems and its orthologs in fungi have been reviewed
• Curated sequence CH_123467: lactate/pyruvate transporter
• Total: 2 characterized proteins

btsT: pyruvate symporter BtsT

• Curated sequence P39396: Pyruvate/proton symporter BtsT; Brenztraubensaure transporter; Pyruvate/H(+) symporter. pyruvate:H⁺ symporter. pyruvate:H⁺ symporter
• Ignore hits to P15078 when looking for 'other' hits (Peptide transporter CstA; Carbon starvation protein A. carbon starvation protein A)
• Comment: formerly yjiY; cstA-like. E. coli cstA (P15078) might be a pyruvate transporter, so ignore
• Total: 1 characterized proteins

mctC: pyruvate symporter MctC

• Curated sequence Q8NS49: Monocarboxylic acid transporter. Pyruvate/acetate/propionate: H+ symporter, MctC (DhlC; cg0953)
• Comment: Note this is related to actP, and was identified by genetics, and is adjacent to a small protein (cg0952) that could be the other subunit (it belongs to DUF485)
• Total: 1 characterized proteins

MCT4: pyruvate symporter MCT4 (SLC16A3)

• Curated sequence O15427: Plasma membrane proton-linked monocarboxylate transporter, MCT4 (SLC16A3). Catalyzes the rapid low affinity plasma membrane transport of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and the ketone bodies acetoacetate, beta-hydroxybutyrate and acetate
• Total: 1 characterized proteins

mctP: pyruvate permease MctP

• Curated sequence Q8VM88: The monocarboxylate uptake (H+ symport?) permease, MctP (transports lactate (Km = 4.4 μM), pyruvate (Km = 3.8), propionate, butyrate (butanoic acid), α-hydroxybutyrate, L- and D-alanine (Km = 0.5 mM), and possibly cysteine and histidine)
• Curated sequence Q1M7A2: Monocarboxylate transport permease protein
• Comment: TCDB and SwissProt have slightly different sequences, include both
• Total: 2 characterized proteins