L-valine catabolism in Bizionia argentinensis JUB59

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 (26 with candidates)

Or see definitions of steps

Step	Description	Best candidate	2nd candidate
brnQ	L-valine:cation symporter BrnQ/BraZ/BraB	BZARG_RS14230
bkdA	branched-chain alpha-ketoacid dehydrogenase, E1 component alpha subunit	BZARG_RS01255	BZARG_RS02455
bkdB	branched-chain alpha-ketoacid dehydrogenase, E1 component beta subunit	BZARG_RS01255	BZARG_RS08025
bkdC	branched-chain alpha-ketoacid dehydrogenase, E2 component	BZARG_RS02185	BZARG_RS08985
lpd	branched-chain alpha-ketoacid dehydrogenase, E3 component	BZARG_RS05855	BZARG_RS00220
acdH	isobutyryl-CoA dehydrogenase	BZARG_RS12915	BZARG_RS01000
ech	(S)-3-hydroxybutanoyl-CoA hydro-lyase	BZARG_RS10395	BZARG_RS02135
bch	3-hydroxyisobutyryl-CoA hydrolase	BZARG_RS10395	BZARG_RS02125
mmsB	3-hydroxyisobutyrate dehydrogenase
mmsA	methylmalonate-semialdehyde dehydrogenase	BZARG_RS04795	BZARG_RS01960
pccA	propionyl-CoA carboxylase, alpha subunit	BZARG_RS05675	BZARG_RS09580
pccB	propionyl-CoA carboxylase, beta subunit	BZARG_RS05670	BZARG_RS01575
epi	methylmalonyl-CoA epimerase	BZARG_RS09430
mcmA	methylmalonyl-CoA mutase, fused catalytic and adenosylcobamide-binding components	BZARG_RS03590	BZARG_RS12055
Alternative steps:
acn	(2R,3S)-2-methylcitrate dehydratase	BZARG_RS02980
acnD	2-methylcitrate dehydratase (2-methyl-trans-aconitate forming)	BZARG_RS02980
Bap2	L-valine permease Bap2
bcaP	L-valine uptake transporter BcaP/CitA
dddA	3-hydroxypropionate dehydrogenase
hpcD	3-hydroxypropionyl-CoA dehydratase	BZARG_RS10395	BZARG_RS02125
iolA	malonate semialdehyde dehydrogenase (CoA-acylating)	BZARG_RS04795	BZARG_RS01960
livF	L-valine ABC transporter, ATPase component 1 (LivF/BraG)	BZARG_RS03265	BZARG_RS01115
livG	L-valine ABC transporter, ATPase component 2 (LivG/BraF)	BZARG_RS03265	BZARG_RS09060
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	BZARG_RS03590	BZARG_RS12055
mcm-small	methylmalonyl-CoA mutase, small (adenosylcobamide-binding) subunit	BZARG_RS03590	BZARG_RS12055
natA	L-valine ABC transporter, ATPase component 1 (NatA)	BZARG_RS03265
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)	BZARG_RS03265	BZARG_RS01115
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	BZARG_RS05675	BZARG_RS09580
pccA2	propionyl-CoA carboxylase, biotin carboxylase subunit
pco	propanyl-CoA oxidase	BZARG_RS08430	BZARG_RS14700
phtJ	L-valine uptake permease PhtJ
prpB	2-methylisocitrate lyase
prpC	2-methylcitrate synthase	BZARG_RS04330
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.