L-valine catabolism in Flaviramulus ichthyoenteri Th78

Best path

brnQ, bkdA, bkdB, bkdC, lpd, acdH, ech, bch, mmsB, mmsA, pccA, pccB, epi, mcmA

Rules

Overview: Valine degradation in GapMind is based on MetaCyc pathway L-valine degradation I (link). The other pathways do not produce any fixed carbon and are not included.

• all: valine-transport, BKD, acdH, ech, bch, mmsB, mmsA and propionyl-CoA-degradation
  • Comment: An aminotransferase (not represented) forms 3-methyl-2-oxobutanoate, the decarboxylating alpha-ketoacid dehydrogenase (BKD) forms isobutanoyl-CoA, dehydrogenase acdH forms methylacrylyl-CoA (2-methylprop-2-enoyl-CoA), the hydratase ech forms (S)-3-hydroxy-isobutaonoyl-CoA, a hydrolase forms (S)-3-hydroxy-isobutanoate, a dehydrogenase forms (S)-methylmalonate semialdehyde (2-methyl-3-oxopropanoate), and a decarboxylating dehydrogenase forms propionyl-CoA.
• BKD:
  • bkdA, bkdB, bkdC and lpd
  • or vorA, vorB and vorC
  • or ofoA and ofoB
  • or ofo
  • Comment: These decarboxylating dehydrogenases act on 4-methyl-2-oxopentanoate, 3-methyl-2-oxobutanoate (2-oxoisovalerate) and (S)-3-methyl-2-oxopentanoate and are known as the branched-chain alpha-ketoacid dehydrogenases. They can pass electrons to NAD (EC 1.2.1.25) or to ferredoxin (EC 1.2.7.7). The NAD-dependent enzyme is the sum of three activities: EC 1.2.4.4 (the 4-methyl-2-oxopentanoate dehydrogenase, with transfer to the lipopoyllysine residue of 2.3.1.168) which is itself heteromeric, with alpha and beta subunits; EC 2.3.1.168 (dihydrolipoyllysine-residue (3-methylbutanoyl)transferase); and EC 1.8.1.4 (dihydrolipoyl dehydrogenase, transferring electrons to NAD). The well-characterized ferredoxin-dependent enzymes have 3 subunits (vorABC) or 2 subunits (ofoAB). Genetic data identified a fused ferredoxin-dependent enzyme with just 1 subunit (ofo).
• propionyl-CoA-degradation:
  • prpC, prpD, acn and prpB
  • or prpC, acnD, prpF, acn and prpB
  • or propionyl-CoA-carboxylase, epi and methylmalonyl-CoA-mutase
  • or pco, hpcD, dddA and iolA
  • Comment: In 2-methylcitrate cycle I, propionyl-CoA is combined with oxalacetate (by prpC) to give methylcitrate, dehydrated to cis-2-methylaconitate by prpD, hydrated to (2R,3S)-2-methylisocitrate, and a lyase produces pyruvate and succinate. (We consider succinate as a central intermediate, as most organisms can activate it to succinyl-CoA or can oxidize it to fumarate and convert that to oxaloacetate.) In 2-methylcitrate cycle II, a different dehydratase (acnD) and an isomerase (prpF) replace the dehydratase prpD; acnD dehydrates (2S,3S)-2-methylcitrate to 2-methyl-trans-aconitate, and prpF isomerizes it to cis-2-methylaconitate. In propanoyl CoA degradation I, propionyl-CoA carboxylase forms (S)-methylmalonyl-CoA, methylmalonyl-CoA epimerase forms (R)-methylmalonyl-CoA, and methylmalonyl-CoA mutase forms succinyl-CoA, which is a central metabolite. (Note that methylmalonyl-CoA mutase requires adenosylcobamide, a form of vitamin B12, for activity.) In propanoyl-CoA degradation II: propionyl-CoA is oxidized to acrylyl-CoA by pco, hydrated to 3-hydroxypropionyl-CoA, hydrolzed to 3-hydroxypropionate, oxidized to 3-oxopropionate (malonate semialdehyde), and oxidized to acetyl-CoA and CO2.
• methylmalonyl-CoA-mutase:
  • mcmA
  • or mcm-large and mcm-small
  • Comment: methylmalonyl-CoA mutase has a catalytic domain and a B12-binding domain. These are usually found in the same protein, which we call mcmA. In Metallosphaera and Pyrococcus, the B12-binding domain is a separate subunit. In Propionibacterium and Methylorubrum, there is an additional subunit with a catalytic domain only; this may have a protective role (PMID:14734568) and is not described here. There's also a mcm-interacting GTPase (known as MeaB or YgfD) that loads B12 onto mcm and protects it from inactivation (see PMC4631608); this is not described here. Some fused mcm proteins include a MeaB domain as well (i.e., Q8F222, Q8Y2U5).
• propionyl-CoA-carboxylase:
  • pccA and pccB
  • or pccA1, pccA2 and pccB
  • Comment: propionyl-CoA carboxylase is a heteromer, usually with alpha and beta subunits pccAB. Haloferax mediterranei has a third subunit as well (pccX), which is not described here. Acidianus brierleyi has a diverged pccA split into two pieces.
• valine-transport:
  • livF, livG, livJ, livH and livM
  • or natA, natB, natC, natD and natE
  • or Bap2
  • or brnQ
  • or phtJ
  • or bcaP
  • Comment: Transporters were identified using query: transporter:valine:L-valine:val

47 steps (25 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
brnQ	L-valine:cation symporter BrnQ/BraZ/BraB	RG22_RS06910
bkdA	branched-chain alpha-ketoacid dehydrogenase, E1 component alpha subunit	RG22_RS16905	RG22_RS05535
bkdB	branched-chain alpha-ketoacid dehydrogenase, E1 component beta subunit	RG22_RS16905	RG22_RS10870
bkdC	branched-chain alpha-ketoacid dehydrogenase, E2 component	RG22_RS04480	RG22_RS09660
lpd	branched-chain alpha-ketoacid dehydrogenase, E3 component	RG22_RS15350	RG22_RS01250
acdH	isobutyryl-CoA dehydrogenase	RG22_RS05640	RG22_RS02810
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	RG22_RS07780	RG22_RS16435
bch	3-hydroxyisobutyryl-CoA hydrolase	RG22_RS07780
mmsB	3-hydroxyisobutyrate dehydrogenase
mmsA	methylmalonate-semialdehyde dehydrogenase	RG22_RS12370
pccA	propionyl-CoA carboxylase, alpha subunit	RG22_RS15140	RG22_RS08620
pccB	propionyl-CoA carboxylase, beta subunit	RG22_RS15135	RG22_RS16470
epi	methylmalonyl-CoA epimerase	RG22_RS08580
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	RG22_RS14270	RG22_RS13630
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	RG22_RS02585
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)
Bap2	L-valine permease Bap2
bcaP	L-valine uptake transporter BcaP/CitA
dddA	3-hydroxypropionate dehydrogenase
hpcD	3-hydroxypropionyl-CoA dehydratase	RG22_RS07780
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	RG22_RS12370
livF	L-valine ABC transporter, ATPase component 1 (LivF/BraG)	RG22_RS04010	RG22_RS03740
livG	L-valine ABC transporter, ATPase component 2 (LivG/BraF)	RG22_RS04010	RG22_RS13220
livH	L-valine ABC transporter, permease component 1 (LivH/BraD)
livJ	L-valine ABC transporter, substrate-binding component (LivJ/LivK/BraC/BraC3)
livM	L-valine ABC transporter, permease component 2 (LivM/BraE)
mcm-large	methylmalonyl-CoA mutase, large (catalytic) subunit	RG22_RS14270	RG22_RS13630
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	RG22_RS14270	RG22_RS13630
natA	L-valine ABC transporter, ATPase component 1 (NatA)	RG22_RS04010	RG22_RS10040
natB	L-valine ABC transporter, substrate-binding component NatB
natC	L-valine ABC transporter, permease component 1 (NatC)
natD	L-valine ABC transporter, permease component 2 (NatD)
natE	L-valine ABC transporter, ATPase component 2 (NatE)	RG22_RS04010
ofo	branched-chain alpha-ketoacid:ferredoxin oxidoreductase, fused
ofoA	branched-chain alpha-ketoacid:ferredoxin oxidoreductase, alpha subunit OfoA
ofoB	branched-chain alpha-ketoacid:ferredoxin oxidoreductase, beta subunit OfoB
pccA1	propionyl-CoA carboxylase, biotin carboxyl carrier subunit	RG22_RS15140	RG22_RS08620
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pco	propanyl-CoA oxidase	RG22_RS06425	RG22_RS05640
phtJ	L-valine uptake permease PhtJ
prpB	2-methylisocitrate lyase
prpC	2-methylcitrate synthase	RG22_RS11555
prpD	2-methylcitrate dehydratase
prpF	methylaconitate isomerase
vorA	branched-chain alpha-ketoacid:ferredoxin oxidoreductase, alpha subunit VorA
vorB	branched-chain alpha-ketoacid:ferredoxin oxidoreductase, beta subunit VorB
vorC	branched-chain alpha-ketoacid:ferredoxin oxidoreductase, gamma subunit VorC

Confidence: high confidence medium confidence low confidence
transporter – transporters and PTS systems are shaded because predicting their specificity is particularly challenging.

This GapMind analysis is from Sep 24 2021. The underlying query database was built on Sep 17 2021.