Metaboliske ændringer hos ME patienter før og efter to dages motion
Efter motion var niveauet af pyrroline-5-carboxylate (P5C) signifikant øget hos kvinder med ME i forhold til raske kontrolpersoner (1).
FC og p-værdier for P5C:
- D1PRE: FC = 1,18, p = 0,10
- D1POST: FC = 1,36, p = 0,009
- D2PRE: FC = 1,20, p = 0,13
- D2POST: FC = 1,72, p = 0,0000122
P5C blev også fundet forhøjet hos ME patienter i Naviaux et al's studie (2).
P5C er et mellemprodukt i omsætning af aminosyrerne prolin, glutamat og ornitin.
Ved iltmangel (hypoxia) fungerer P5C og prolin som et redoxpar, der påvirker NADP+/NADPH ratioen (3):
Figure 1. The metabolic pathways of P5C—physiological intracellular intermediate of the interconversion of proline, ornithine, and glutamate. Acetyl-CoA—acetyl coenzyme A, ATP—adenosine triphosphate, α-KG—α-ketoglutarate, Glu—glutamate, GSAL—L-glutamate-γ-semialdehyde, METC—mitochondrial electron transport chain, NAD+—oxidized form of nicotinamide adenine dinucleotide, NADH—reduced form of nicotinamide adenine dinucleotide, NADP+ –oxidized form of nicotinamide adenine dinucleotide phosphate, NADPH—reduced form of nicotinamide adenine dinucleotide phosphate, ORN—ornithine, P5C—∆ 1 -pyrroline-5-carboxylate, P5CDH—P5C dehydrogenase, P5CS—P5C synthase, PAT1—proton-coupled amino acid transporter 1, PRODH/POX—proline dehydrogenase/oxidase, PROT—L-proline transporter PROT, PYCR1/2/L—P5C reductase 1/2/L, ROS—reactive oxygen species, SIT1—sodium/imino-acid transporter 1, SNAT1/2—sodium-coupled neutral amino acid transporter 1/2, TCA cycle—tricarboxylic acid cycle, δOAT—ornithine δ-aminotransferase. Reference: Chalecka M, Kazberuk A, Palka J, Surazynski A. P5C as an Interface of Proline Interconvertible Amino Acids and Its Role in Regulation of Cell Survival and Apoptosis. Int J Mol Sci. 2021 Oct 29;22(21):11763. doi: 10.3390/ijms222111763. PMID: 34769188; PMCID: PMC8584052. https://www.mdpi.com/1422-0067/22/21/11763
Efter motion på 2. dagen var niveauet af proline signifikant øget hos kvinder med ME i forhold til raske kontrolpersoner (1):
FC og p-værdier for proline:
- D1PRE: FC = 1,03, p = 0,76
- D1POST: FC = 1,04, p = 0,88
- D2PRE: FC = 1,15, p = 0,13
- D2POST: FC = 1,18, p = 0,03
Pyrroline-5-carboxylate synthase (P5CS) katalyserer syntesen af P5C. P5CS mærker cellestress og tilpasser metabolismen ved at regulere mitokondriel respiration. P5CS er nødvendig for den oxidative respiration i mitokondrierne (4).
Hvad betyder det øgede niveau af P5C og proline hos ME patienter? Har det forbindelse til hypoxia? Stiger niveauet af P5C, fordi den oxidative respiration i mitokondrierne er udfordret af ME sygdom-mekanismen?
Læs også:
Lav arteriel-venøs iltindhold difference hos ME patienter
Andre gode artikler om P5C:
Proline synthesis through PYCR1 is required to support cancer cell proliferation and survival in oxygen-limiting conditions
Perspectives, past, present and future: the proline cycle/proline-collagen regulatory axis
Læs også:
Lav arteriel-venøs iltindhold difference hos ME patienter
Proline synthesis through PYCR1 is required to support cancer cell proliferation and survival in oxygen-limiting conditions
Perspectives, past, present and future: the proline cycle/proline-collagen regulatory axis
Referencer
1) Germain A, Giloteaux L, Moore GE, Levine SM, Chia JK, Keller BA, Stevens J, Franconi CJ, Mao X, Shungu DC, Grimson A, Hanson MR. Plasma metabolomics reveals disrupted response and recovery following maximal exercise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. JCI Insight. 2022 Mar 31:e157621. doi: 10.1172/jci.insight.157621. Epub ahead of print. PMID: 35358096.
2) Naviaux RK, Naviaux JC, Li K, Bright AT, Alaynick WA, Wang L, Baxter A, Nathan N, Anderson W, Gordon E. Metabolic features of chronic fatigue syndrome. Proc Natl Acad Sci U S A. 2016 Sep 13;113(37):E5472-80. doi: 10.1073/pnas.1607571113. Epub 2016 Aug 29. Erratum in: Proc Natl Acad Sci U S A. 2017 May 2;114(18):E3749. PMID: 27573827; PMCID: PMC5027464.
3) Chalecka M, Kazberuk A, Palka J, Surazynski A. P5C as an Interface of Proline Interconvertible Amino Acids and Its Role in Regulation of Cell Survival and Apoptosis. Int J Mol Sci. 2021 Oct 29;22(21):11763. doi: 10.3390/ijms222111763. PMID: 34769188; PMCID: PMC8584052.
4) Yang Z, Zhao X, Shang W, Liu Y, Ji JF, Liu JP, Tong C. Pyrroline-5-carboxylate synthase senses cellular stress and modulates metabolism by regulating mitochondrial respiration. Cell Death Differ. 2021 Jan;28(1):303-319. doi: 10.1038/s41418-020-0601-5. Epub 2020 Aug 7. PMID: 32770108; PMCID: PMC7853148.
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