NAD(P) metabolic process terms

[sjm41]

We currently have this arrangement:

NAD metabolic process
|__NAD biosynthetic process
|__NAD catabolic process
|__NADH metabolic process
    |__NADH oxidation
    |__NADH regeneration

NADP metabolic process
|__NADP biosynthetic process
|__NADP catabolic process
|__NADPH oxidation
|__NADPH regeneration

And here are the terms:

id: GO:0019674
name: NAD metabolic process
def: "The chemical reactions and pathways involving nicotinamide adenine dinucleotide (NAD), a coenzyme present in most living cells and derived from the B vitamin nicotinic acid." [GOC:jl, ISBN:0618254153]
intersection_of: GO:0008152 ! metabolic process
intersection_of: has_primary_input_or_output CHEBI:13389 ! NAD
property_value: term_tracker_item "#21577" xsd:anyURI
property_value: term_tracker_item "#23467" xsd:anyURI

id: GO:0009435
name: NAD biosynthetic process
def: "The chemical reactions and pathways resulting in the formation of nicotinamide adenine dinucleotide, a coenzyme present in most living cells and derived from the B vitamin nicotinic acid; biosynthesis may be of either the oxidized form, NAD, or the reduced form, NADH." [GOC:jl, ISBN:0618254153]
intersection_of: GO:0009058 ! biosynthetic process
intersection_of: has_primary_output CHEBI:13389 ! NAD
property_value: term_tracker_item "#21577" xsd:anyURI

id: GO:0019677
name: NAD catabolic process
def: "The chemical reactions and pathways resulting in the breakdown of nicotinamide adenine dinucleotide, a coenzyme present in most living cells and derived from the B vitamin nicotinic acid; catabolism may be of either the oxidized form, NAD, or the reduced form, NADH." [GOC:jl, ISBN:0618254153]
intersection_of: GO:0009056 ! catabolic process
intersection_of: has_primary_input CHEBI:13389 ! NAD
property_value: term_tracker_item "#21577" xsd:anyURI

id: GO:0006734 (28 direct EXP annotations)
name: NADH metabolic process
def: "The chemical reactions and pathways involving reduced nicotinamide adenine dinucleotide (NADH), a coenzyme present in most living cells and derived from the B vitamin nicotinic acid." [GOC:jl, ISBN:0618254153]
intersection_of: GO:0008152 ! metabolic process
intersection_of: has_primary_input_or_output CHEBI:57945 ! NADH(2-)

id: GO:0006116 (25 direct EXP annotations)
name: NADH oxidation
def: "A metabolic process that results in the oxidation of reduced nicotinamide adenine dinucleotide, NADH, to the oxidized form, NAD+." [GOC:ai]
intersection_of: GO:0008152 ! metabolic process
intersection_of: has_primary_input CHEBI:57945 ! NADH(2-)
intersection_of: has_primary_output CHEBI:57540 ! NAD(1-)
property_value: term_tracker_item "#21577" xsd:anyURI

id: GO:0006735 (9 direct EXP annotations)
name: NADH regeneration
def: "A metabolic process that generates a pool of NADH by the reduction of NAD+." [GOC:mah]
intersection_of: GO:0008152 ! metabolic process
intersection_of: has_output CHEBI:57945 ! NADH(2-)
intersection_of: has_primary_input CHEBI:57540 ! NAD(1-)
intersection_of: has_primary_output CHEBI:57945 ! NADH(2-)

---

id: GO:0006739
name: NADP metabolic process
def: "The chemical reactions and pathways involving nicotinamide-adenine dinucleotide phosphate, a coenzyme involved in many redox and biosynthetic reactions; metabolism may be of either the oxidized form, NADP, or the reduced form, NADPH." [GOC:mah]
intersection_of: GO:0008152 ! metabolic process
intersection_of: has_primary_input_or_output CHEBI:58349 ! NADP(3-)
property_value: term_tracker_item "#23467" xsd:anyURI

id: GO:0006741
name: NADP biosynthetic process
def: "The chemical reactions and pathways resulting in the formation of nicotinamide-adenine dinucleotide phosphate, a coenzyme involved in many redox and biosynthetic reactions; biosynthesis may be of either the oxidized form, NADP, or the reduced form, NADPH." [GOC:mah]
intersection_of: GO:0009058 ! biosynthetic process
intersection_of: has_primary_output CHEBI:58349 ! NADP(3-)

id: GO:0006742
name: NADP catabolic process
def: "The chemical reactions and pathways resulting in the breakdown of nicotinamide-adenine dinucleotide phosphate, a coenzyme involved in many redox and biosynthetic reactions; catabolism may be of either the oxidized form, NADP, or the reduced form, NADPH." [GOC:mah]
intersection_of: GO:0009056 ! catabolic process
intersection_of: has_primary_input CHEBI:58349 ! NADP(3-)

id: GO:0070995 (16 direct EXP annotations)
name: NADPH oxidation
def: "A metabolic process that results in the oxidation of reduced nicotinamide adenine dinucleotide, NADPH, to the oxidized form, NADP." [GOC:BHF, GOC:mah]
is_a: GO:0006739 ! NADP metabolic process
intersection_of: GO:0008152 ! metabolic process
intersection_of: has_primary_input CHEBI:57783 ! NADPH(4-)
intersection_of: has_primary_output CHEBI:58349 ! NADP(3-)

id: GO:0006740 (24 direct EXP annotations)
name: NADPH regeneration
def: "A metabolic process that generates a pool of NADPH by the reduction of NADP+." [GOC:mah]
is_a: GO:0006091 ! generation of precursor metabolites and energy
is_a: GO:0006739 ! NADP metabolic process
intersection_of: GO:0008152 ! metabolic process
intersection_of: has_primary_input CHEBI:58349 ! NADP(3-)
intersection_of: has_primary_output CHEBI:57783 ! NADPH(4-)

---

I think there are several issues to address here:

• In all these defs, "the oxidized form" should be reported as 'NAD+' or ''NADP+' rather than just 'NAD' or 'NADP'.

• For the 'NAD metabolic process' term def, should add "metabolism may be of either the oxidized form, NAD+, or the reduced form, NADH." to match the defs of the child 'NAD biosynthetic/catabolic process' terms as well as the def of the equivalent 'NADP metabolic process' term.

• Implementing the point above would make the "NADH metabolic process" term redundant, so it should be obsoleted (or rather merged into the parent 'NAD metabolic process' term). Doing so would also then match how the NADP branch is already organised.

• As alluded to in malate-aspartate shuttle parentage #27924, "NADH oxidation" and "NADPH oxidation" are just inevitable consequences of these factors acting as co-enzymes for oxidoreductase enzymes - I can't see any utility in having these terms (as defined), since they could be applied to any oxidoreductase reaction using NAD(P)H and operating in the reductase direction. Suggest these two terms are obsoleted.

• Change the primary_input/output chemical on the NAD metabolic/biosynthesis/catabolic terms from 'CHEBI:13389 ! NAD' to 'CHEBI:57540 ! NAD(1-)' to be consistent with how this is reported in the other terms mentioned above. (This was meant to be fixed in Change logical definition of 'GO:0019674 NAD metabolic process #23467, but doesn't look like it actually happened.)

• The LD of the 'NADH regeneration' term has the same CHEBI as both 'has_output' and 'has_primary_output' - remove the former.

• The 'NADPH regeneration' term appears to have a "is_a: GO:0006739 ! NADP metabolic process" relation that is redundant with the LD - need to check and remove if so.

I found PMID:28648096 is a good general review of NAD(H) and NADP(H) biology, including synthetic pathways.

@rozaru @deustp01 @ukemi