PathwayMap:GlycerolipidBiosynthesis

2018-04-26T07:42:42Z

Mitsuharu:

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[title] <2.5,2.5>
#Glycerolipid Metabolome
de novo pathway of glycerophospholipid

//titles
[OMM_name] <88.5,42.5>css(font-size:40px;background:rgb(200,200,150;border:5px solid black;color:)
Mitochondrial outer membrane

[IMM_name] <88.5,35>css(font-size:40px;background:rgb(200,200,150;border:5px solid black;color:)
Mitochondrial inner membrane

[ER] <6,113.5>css(font-size:40px;background:rgb(200,200,150;border:5px solid black;z-index:2)
Endoplasmic reticulum

//=========================================Organelles======================================================
//Mitochondria outer membrane
[OMM] <38.5,2.5,2100,700>css(background:rgb(255,200,50;z-index:1;border:30px solid rgb(155,100,10)

//Mitochondria inner membrane
[IMM] <57.5,17.5,1500,350>css(background:rgb(255,200,50;z-index:2;border:30px solid rgb(155,100,10)

//Endoplasmic reticulum
[ER1] <1,1,400,2050>css(background:rgb(200,255,10;border-right:50px solid rgb(200,200,0;box-shadow:none;z-index:1)

//Golgi
[Golgi] <39,51.5,700,1000>css(background:rgb(50,140,140;border:30px solid rgb(100,200,200;box-shadow:none;z-index:1)

//=========================================Metabolites=====================================================
//glycerol-3-phosphate
[G3P3] <29.5,1.5>
!GL{OH |OH|O-PO_s3s_}
?[link](http://lipidbank.jp/cgi-bin/main.cgi?id=PGP "G3P")
d=(l_w5)=>u[LPA]
d=(l_w5)=>u[LPAmt]

//lysophosphatidic acid
[LPA] <22.5,13>
!GL{O-CO-R1|OH|O-PO_s3s_}
LPA
d=(l_w5)=>u[PAER]

//lysophosphatidic acid
[LPAmt] <36.5,13>
!GL{O-CO-R1|OH|O-PO_s3s_}
LPA
d=(l_w5)=>u[PA2]

//phosphatidic acid, mitochondrial
[PAER] <23,32>
!GL{O-CO-R1|O-CO-R2|O-PO_s3s_}
?[link](http://jcbl.jp/wiki/Volatile:ListMol?my_1=LBGPA"PA")
d=(l_w5)=>u[DAG2]
d=(l_w5)=>u[CDP-DAGer]

//phosphatidic acid, mitochondrial
[PAmt] <54,15>
!GL{O-CO-R1|O-CO-R2|O-PO_s3s_}
?[link](http://jcbl.jp/wiki/Volatile:ListMol?my_1=LBGPA"PA")
r=(l_w5)=>l[CDP-DAG]

//cytidine diphosphate-diacylglycerol
[CDP-DAG] <73,15>
!GL{O-CO-R1 | O-CO-R2 | O-PO2-CMP</t>}
CDP-DAG
r=(l_w5)=>l[PGP]

//cytidine diphosphate-diacylglycerol
[CDP-DAGer] <22,60>
!GL{O-CO-R1 | O-CO-R2 | O-PO2-CMP</t>}
CDP-DAG
r=(l_w5)=>u[PI]
d=(l_w5)=>u[PI2]
//cytidine triphosphate
[CTP] <64,14.5>
CTP
d=(l_w2)=>d[PPi]

//pyrophosphate
[PPi] <68.5,13>
pyrophosphate

//phosphatidylglycerol-phosphate
[PGP] <96,14>
!PG{O-CO-R1 | O-CO-R2 | O-PO2-O| HO|O3P-O}
PGP
r=(l_w4)=>l[PG]

//glycerol-3-phosphate
[G3P] <82.5,9>
!GL{OH |OH|O-PO_s3s_}
?[link](http://lipidbank.jp/cgi-bin/main.cgi?id=PGP "G3P")
d=(l_w2)=>d[CMP]

[CMP] <90.5,13>
CMP

[PG] <118,13.5>
!PG{O-CO-R1 | O-CO-R2 | PO2-O| HO|HO }
?[link](http://jcbl.jp/wiki/Volatile:ListMol?my_1=LBGPG"PG")

r=(l_w4)=>[CL]
[H2O] <109,14>
H2O
d=(l_w2)=>d[Pi]

[Pi] <113,14>
Pi

[CDP-DAGbox] <128,13.5>
CDP-DAG
d=(l_w2)=>d[CMP2]

[CMP2] <134.5,13.5>
CMP

//cardiolipin
[CL] <138,12>
!CL{O-CO-R1|O-CO-R2|O-PO-O|HO|O-PO-O|O-CO-R3| O-CO-R4}
CL
u=(l_w5)=>d[CL2]

[CL2] <142,3>
CL

[PA2] <37,23.5>
!GL{O-CO-R1|O-CO-R2|O-PO_s3s_}
PA
=(l_w5)=>[PAmt]

//diacylglycerol
[DAG] <54,28>
!GL{O-CO-R1|O-CO-R1| OH}
DAG
u=(l_w5)=>d[PAmt]

[unknown] <53,38>
?
u==>d[DAG]

//diacylglycerol
[DAG2] <22,48.5>
!GL{O-CO-R1|O-CO-R1| OH}
DAG
r=(l_w5)=>[PC]

//phosphatidylinositol
[PI] <33.5,76>
!GL{O-CO-R1 | O-CO-R2 | O-PO2-Inositol}
?[link](http://jcbl.jp/wiki/Volatile:ListMol?my_1=LBGPI"PI")

//phosphatidylinositol
[PI2] <21.5,76>
!GL{O-CO-R1 | O-CO-R2 | O-PO2-Inositol}
?[link](http://jcbl.jp/wiki/Volatile:ListMol?my_1=LBGPI"PI")

//phosphatidylcholine
[PC] <53.5,48.5>
!GL{O-CO-R1|O-CO-R2|O-PO2-Choline}
?[link](http://jcbl.jp/wiki/Volatile:ListMol?my_1=LBGPC"PC")

//phosphatidylethanolamine
[PE] <24,92.5>
!GL{O-CO-R1|O-CO-R2| O-PO2-Ethanolamine}
PE

//===================================Gene====================================================
[Tam41] <66,17>css(background:rgb(255,200,50;border:5px solid rgb(255,100,50;z-index:5)
Tam41

<pop>
Enzyme: CDP-diacylglycerol synthase<br>
<nobr>This reaction is not catalyzed by Cds1 in mitochondria.
?[link](http://www.cell.com/cell-metabolism/pdf/S1550-4131(13)00142-3.pdf"Tamura et al. 2013. Cell Metab. 17(5):709-718.")
</pop>

//phosphatidylglycerolphosphate (PGP) synthase
[aa] (gene) <87,16.5>css(background:rgb(255,200,50;border:5px solid rgb(255,100,50;z-index:5)
PGS1

//phosphatidylglycerophosphatase
[PTPMT1] <109.5,17.5>css(background:rgb(255,200,50;border:5px solid rgb(255,100,50;z-index:5)
PTPMT1

//cardiolipin synthase
[CRLS1] <130.5,17>css(background:rgb(255,200,50;border:5px solid rgb(255,100,50;z-index:5)
CRLS1

[PRELITRIAP1] <45.5,21>css(background:rgb(255,200,50;border:5px solid rgb(255,100,50;z-index:5)
Transferred by
PRELI1 + TRIAP1

<pop>
<nobr>In yeast Ups1 shuffles PA between the OMM and IMM and the PA-loaded Ups1 needs the interaction with Mdm35 for stabilisation.
?[link](http://science.sciencemag.org/cgi/pmidlookup?view=long&pmid=23042293"Connerth et al. 2012. Science. 338(6108):815-818.")
In human, the orthologous gene of Ups1 is PRELI1 and TRIAP1 is the gene which has the function of Mdm35.
?[link](https://linkinghub.elsevier.com/retrieve/pii/S1550-4131(13)00297-0"Potting et al. 2013. Cell Metab. 18(2):287-295.")
</pop>

//nucleoside diphosphate kinase Nm23-H4
[NME4] <139.5,7>css(background:rgb(255,200,50;border:5px solid rgb(255,100,50;z-index:5)
Transffered by
Nm23-H4
<pop>
<nobr>The nucleoside diphosphate kinase Nm23-H4 (encoded by the NME4 gene) localizes in the mitochondrial inter-membrane space
and seems to have a dual function either in the transfer of phosphate groups or in the transfer of CL from the IMM to the OMM.
?[link](https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23150663/"Schlattner et al. 2013. J Biol Chem. 288(1):111-121.")
</pop>

//acylglycerol kinase
[AGK] <56.5,24>css(background:rgb(255,200,50;border:5px solid rgb(255,100,50;z-index:5)
AGK
<pop>
<nobr>There is a term "Multi-substrate lipid kinase (MuLK)" (Waggoner et al., 2004).
This enzyme phosphorylates diacylglycerol, ceramide, and 1-acylglycerol but not sphingosine.
?[link](http://www.jbc.org/content/279/37/38228.long"Waggoner et al. 2004. J Biol Chem. 279(37):38228-38235.")

AGK deficiency results in Sengers syndrome with dysfunction of the mitochondrial energy metabolism.

?[link](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3523805/"Calvo et al. 2012. Sci Transl Med. 4(118):118ra10.")
?[link](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276657/"Mayr et al. 2012. Am J Hum Genet. 90(2):314-320.")

</pop>

[GPATer] <24.5,9>css(background:rgb(255,200,50;border:5px solid rgb(255,100,50;z-index:5)
GPAT3,4

[GPATmit] <35.5,9>css(background:rgb(255,200,50;border:5px solid rgb(255,100,50;z-index:5)
GPAT1,2

[AGPAT] <36.5,20>css(background:rgb(255,200,50;border:5px solid rgb(255,100,50;z-index:5)
AGPAT1,4

[AGPAT2] <22,24>css(background:rgb(255,200,50;border:5px solid rgb(255,100,50;z-index:5)
AGPAT1,2,3,5

//Phosphatidate phosphatase
[LPIN] <23,42.5>css(background:rgb(255,200,50;border:5px solid rgb(255,100,50;z-index:5)
LPIN
?[link](http://www.genome.jp/dbget-bin/www_bget?ec:3.1.3.4"KEGG")
<pop>
Phosphatidate phosphatase
</pop>

//CDP-diacylglycerol--inositol 3-phosphatidyltransferase
[CDIPT] <36.5,69>css(background:rgb(255,200,50;border:5px solid rgb(255,100,50;z-index:5)
CDIPT
?[link](http://www.genome.jp/dbget-bin/www_bget?ec:2.7.8.11"KEGG")

//CDP-diacylglycerol--inositol 3-phosphatidyltransferase
[CDIPT2] <24,69>css(background:rgb(255,200,50;border:5px solid rgb(255,100,50;z-index:5)
CDIPT
?[link](http://www.genome.jp/dbget-bin/www_bget?ec:2.7.8.11"KEGG")

//Cholinephosphotransferase
[CHPT1] <44,48.5>css(background:rgb(255,200,50;border:5px solid rgb(255,100,50;z-index:5)
CHPT
?[link](http://www.genome.jp/dbget-bin/www_bget?ec:2.7.8.2"KEGG")
?[link](http://www.uniprot.org/uniprot/Q8WUD6"UniProt")

<pop>
<nobr>Subcellular localization
?[link](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC124149/"Henneberry et al.( 2002) Mol Biol Cell. 13(9):3148-3161")
</pop>

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PathwayMap:GlycerolipidBiosynthesis