Table 1.
Pathways altered in Parkinson’s disease patients and LRRK2 mutation carriers
| ID | Lipids | |
|---|---|---|
| Pathway altered in Parkinson’s disease | ||
| Glycerophospholipid metabolism | [map00564] | LPC, LPE, PC, PE |
| Sphingolipid metabolism | [map00600] | Cer, CerP, SM |
| Oxidative phosphorylation and thermogenesis | [map04714] | AcCa, TG |
| Glycogen production, GLUT4 translocation and glucose uptake (Insulin resistance) | [map04931] | Cer, TG |
| Sphingolipid signalling | [map04071] | Cer, SM |
| Necroptosis | [map04217] | Cer, SM |
| Retrograde endocannabinoid signalling | [map04723] | PC, PE |
| Pathways altered in LRRK2 G2019S mutation carriers | ||
| Glycerophospholipid metabolism | [map00564] | DG, LPC, LPE, PC |
| Sphingolipid metabolism | [map00600] | Cer, Hex1Cer,a SM |
| Oxidative phosphorylation and thermogenesis | [map04714] | AcCa, DG, TG |
| Glycogen production, GLUT4 translocation and glucose uptake (insulin resistance) | [map04931] | Cer, DG, TG |
| Glycerolipid metabolism | [map00561] | DG, MGDG, TG |
| Retrograde endocannabinoid signalling | [map04723] | DG, PC |
| Regulation of lipolysis in adipocytes | [map04923] | DG, TG |
| Fat digestion and absorption | [map04975] | DG, TG |
| Adipocytokine signalling pathway | [map04920] | Cer, DG |
| Necroptosis | [map04217] | Cer, SM |
| Sphingolipid signalling | [map04071] | Cer, SM |
| Neurotrophin signalling pathway | [map04722] | Cer, DG |
| Advanced glycation end products (AGE) signalling | [map04933] | Cer, DG |
Lipid subclasses of interest from the serum analyses were searched in the online KEGG compound/pathway database (Kanehisa et al.38) to identify whether lipids of interest were enriched in certain pathways. Pathways that were shared by at least two lipids are listed above. GLUT4 = Glucose transporter type 4, insulin-responsive. Glycogen production, GLUT4 translocation and glucose uptake are subpathways in an ‘insulin resistance’ pathway. Oxidative phosphorylation and thermogenesis is from ‘thermogenesis’ pathway. AcCa = acylcarnitine; LPE = lysophosphatidylethanolamine; MGDG = monogalactosyldiacylglycerol.
Glucosylceramide and galactosylceramide were entered as the search terms for monohexoyslceramide (Hex1Cer) as the data obtained from LC-MS/MS do not allow these to be discriminated. Glycerophospholipid is synonymous with phospholipid.