Definition of ethanol catabolism
As rules and steps, or see full text
Rules
Overview: Ethanol can pass through biological membranes, so no transporter is required. Ethanol degradation in GapMind is based on MetaCyc pathways ethanol degradation I (oxidation to acetyl-CoA, link) and II (oxidation to acetate and activation, link). Pathways III (with ethanol monooxygenase, link) and IV (with ethanol peroxidase, link) are not reported to occur in prokaryotes and are not included.
- all: etoh-dh and acetaldehyde-degradation
- Comment: Ethanol is consumed by oxidation to acetaldehyde
- acetaldehyde-degradation:
- ald-dh-CoA
- or adh and acs
- or adh, ackA and pta
- Comment: Acetaldehyde can be oxidized to acetyl-CoA, or oxidized to acetate and activated to acetyl-CoA by either acetyl-CoA synthetase (acs) or by acetate kinase (ackA) and phosphate acetyltransferase (pta).
- etoh-dh:
- etoh-dh-nad
- or etoh-dh-c
- or etoh-dh-qn
- Comment: Three types of ethanol dehydrogenases: NAD(P) dependent, cytochrome c dependent, or quinone dependent.
- etoh-dh-qn: adhAqn, adhBqn and adhSqn
- Comment: Bacterial quinone-dependent enzymes (EC 1.1.5.5) have 3 subunits.
Steps
etoh-dh-nad: ethanol dehydrogenase (NAD(P))
- Curated proteins or TIGRFams with EC 1.1.1.1
- Ignore hits to CH_121261 when looking for 'other' hits (NAD-dependent alcohol dehydrogenase; EC 1.1.1.1)
- Curated proteins or TIGRFams with EC 1.1.1.71
- Comment: CH_121261 seems to be a sequence fragment
- Total: 126 characterized proteins
etoh-dh-c: ethanol dehydrogenase (cytochrome c)
adhAqn: ethanol dehydrogenase (quinone), subunit I
- Curated sequence Q44002: alcohol dehydrogenase (quinone) (EC 1.1.5.5)
- Curated sequence P18278: alcohol dehydrogenase (quinone) (EC 1.1.5.5)
- Curated sequence Q93RE9: alcohol dehydrogenase (quinone) (EC 1.1.5.5)
- Curated sequence O05542: Alcohol dehydrogenase (quinone), dehydrogenase subunit; ADH; Alcohol dehydrogenase (quinone), acceptor subunit; Alcohol dehydrogenase (quinone), subunit I; Ethanol:Q2 reductase; G3-ADH subunit I; Quinohemoprotein alcohol dehydrogenase; Quinohemoprotein-cytochrome c complex; Ubiquinol oxidase; EC 1.1.5.5. alcohol dehydrogenase acceptor subunit (EC 1.1.5.5)
- Curated sequence P28036: Alcohol dehydrogenase (quinone), dehydrogenase subunit; ADH; Alcohol dehydrogenase (quinone), acceptor subunit; Alcohol dehydrogenase (quinone), subunit I; Ethanol:Q2 reductase; G3-ADH subunit I; Quinohemoprotein alcohol dehydrogenase; Quinohemoprotein-cytochrome c complex; Ubiquinol oxidase; EC 1.1.5.5
- Ignore hits to items matching 1.1.2.8 when looking for 'other' hits
- Comment: (The enzyme from Zymomonas is NAD-dependent, but is misannotated as quinone-dependent in MetaCyc.)
- Total: 5 characterized proteins
adhBqn: ethanol dehydrogenase (quinone), subunit II
- Curated sequence P0A388: Alcohol dehydrogenase (quinone), cytochrome c subunit; ADH; Alcohol dehydrogenase (quinone), subunit II; Cytochrome c-553; Cytochrome c553; Ethanol:Q2 reductase; G3-ADH subunit II; Quinohemoprotein-cytochrome c complex; Ubiquinol oxidase; EC 1.1.5.5
- Curated sequence Q47945: Alcohol dehydrogenase (quinone), cytochrome c subunit; ADH; Alcohol dehydrogenase (quinone), subunit II; Cytochrome c-553; Cytochrome c553; Ethanol:Q2 reductase; G3-ADH subunit II; Quinohemoprotein-cytochrome c complex; Ubiquinol oxidase; EC 1.1.5.5. alcohol dehydrogenase cytochrome c subunit (EC 1.1.5.5)
- Ignore hits to items matching 1.1.2.8 when looking for 'other' hits
- Total: 2 characterized proteins
adhSqn: ethanol dehydrogenase (quinone), subunit III
- Curated sequence O05544: Alcohol dehydrogenase, 15 kDa subunit; Alcohol dehydrogenase (quinone), subunit III; G3-ADH subunit III. alcohol dehydrogenase 15 kDa subunit (EC 1.1.5.5)
- Total: 1 characterized proteins
ald-dh-CoA: acetaldehyde dehydrogenase, acylating
- Curated proteins or TIGRFams with EC 1.2.1.10
- Ignore hits to items matching 1.1.1.1 when looking for 'other' hits
- Ignore hits to items matching 1.1.1.71 when looking for 'other' hits
- Ignore hits to items matching 1.2.1.57 when looking for 'other' hits
- Ignore hits to Q2XQZ7 when looking for 'other' hits (4-hydroxy-2-oxovalerate aldolase (EC 4.1.3.39))
- Comment: Many enzymes are multifunctional alcohol/acetaldehyde dehydrogenases, and many close homologs have just one annotation. EC 1.2.1.57 is acylating butanal dehydrogenase, which may also act on acetaldehyde. Q2XQZ7 is probably misannotated.
- Total: 2 HMMs and 20 characterized proteins
adh: acetaldehyde dehydrogenase (not acylating)
acs: acetyl-CoA synthetase, AMP-forming
ackA: acetate kinase
pta: phosphate acetyltransferase
- Curated proteins or TIGRFams with EC 2.3.1.8
- Ignore hits to P32796 when looking for 'other' hits (carnitine O-acetyltransferase (EC 2.3.1.7); phosphate acetyltransferase (EC 2.3.1.8). Carnitine O-acetyltransferase, mitochondrial; Carnitine acetylase; EC 2.3.1.7)
- Comment: BRENDA misannotates yeast's carnitine acetyltransferase with EC 2.3.1.8
- Total: 1 HMMs and 18 characterized proteins
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About GapMind
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:
- ublast finds a hit to a characterized protein at above 40% identity and 80% coverage, and bits >= other bits+10.
- (Hits to curated proteins without experimental data as to their function are never considered high confidence.)
- HMMer finds a hit with 80% coverage of the model, and either other identity < 40 or other coverage < 0.75.
where "other" refers to the best ublast hit to a sequence that is not annotated as performing this step (and is not "ignored").
Otherwise, a candidate is "medium confidence" if either:
- ublast finds a hit at above 40% identity and 70% coverage (ignoring otherBits).
- ublast finds a hit at above 30% identity and 80% coverage, and bits >= other bits.
- HMMer finds a hit (regardless of coverage or other bits).
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:
- our ignorance of proteins' functions,
- omissions in the gene models,
- frame-shift errors in the genome sequence, or
- the organism lacks the pathway.
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