GPRs for MAR09985 and MAR11307

[Devlin-Moyer]

Background:

Both reactions currently have no genes associated with them:
MAR09985: 5-aminolevulinate [c] + 2 H+ [c] ⇔ 5-aminolevulinate [e] + 2 H+ [e]
MAR11307: 5-aminolevulinate [c] + H+ [c] ⇔ 5-aminolevulinate [e] + H+ [e]
According to Uniprot, SLC15A1 (ENSG00000088386) can catalyze either of these reactions, and SLC36A1 (ENSG00000123643) can catalyze MAR11307 but not MAR09985. Both of these genes are already in Human-GEM and associated with many other similar reactions.

Proposed Changes:

• Add ENSG00000088386 to the currently empty GPR of MAR09985
• Add ENSG00000088386 or ENSG00000123643 to the currently empty GPR of MAR11307

[haowang-bioinfo]

based on catalytic activity of SLC15A1 and SLC36A1, direct evidence supporting 5-aminolevulinate as substrate is lacking

[Devlin-Moyer]

Oh whoops I meant to cite this paper and not just Uniprot for this

[haowang-bioinfo]

Oh whoops I meant to cite this paper and not just Uniprot for this

yes, this paper reports that SLC15A1 and SLC36A1 contribute to proton-coupled transport of 5-aminolevulinate in the intestine.

I wonder if the transport is in/out for a tissue, or across intestine from/to lumen (I can't access the paper's content)?

[Devlin-Moyer]

It appears to be out of the intestinal lumen into the cells lining the intestines (from the last paragraph of the intro):

There is convincing evidence that the intestinal H+-coupled di/tripeptide transporter PepT1 (SLC15A1) can transport ALA (Döring et al., 1998) and so may be involved in ALA transport across the intestinal epithelial brush-border membrane. [...] To test this hypothesis, ALA transport by the H+-coupled amino acid transporter PAT1 (SLC36A1) (Boll et al., 2002; Chen et al., 2003) was measured. PAT1 mediates uptake of GABA, other small neutral amino acids (e.g., proline, glycine, and taurine), and a large number of related amino acid analogs across the apical membrane of intestinal epithelial cells (Thwaites et al., 1995, 2000; Anderson et al., 2004; Metzner et al., 2006; Thwaites and Anderson, 2007a). [...] PAT1 transport, like that of PepT1, is driven by the H+ electrochemical gradient that exists because of an area of low pH adjacent to the intestinal luminal surface, called the acid microclimate (McEwan et al., 1988; Thwaites and Anderson, 2007b). By using a combination of heterologous expression in Xenopus laevis oocytes and endogenous expression in Caco-2 cell monolayers, we show that PAT1 is a novel pH-dependent, rheogenic H+/ALA transporter and that both PAT1 and PepT1 contribute to ALA uptake across the brush-border membrane of intestinal epithelial cells.

[haowang-bioinfo]

It appears to be out of the intestinal lumen into the cells lining the intestines

then please go ahead to make the change

[haowang-bioinfo]

fixed in #623