Regulation of Metabolic Activity
3 important questions on Regulation of Metabolic Activity
Where does HIF act upon? Name the 3 different groups.
It binds to hypoxia responsive elements in target genes. There are 3 gene/protein groups:
1: erythropoiesis (RBC and Fe metabolism)
2: local O2 delivery in tissues (vascularization)
3: metabolic adaptation to low O2
How is HIF-1a regulated during normoxia?
Posttranslational modification by PHD and FIH, adding OH-groups (hydroxylation)
binding by the von Hippel-Landau (VHL) tumor suppressor -> ubiquitination -> degradation by the proteasome.
Regulation at protein level: HIF-1a is constitutively expressed and immediatly degraded, so it will only function if it's not.
How is HIF-1a regulated during hypoxia? What does HIF-1a do upon activation (4)?
hydroxylation by PHD is inhibited by ROS. FIH is inhibited by hypoxia: full transcriptional activity of HIF-1a.
1: lipid + nucleotide biosynthesis
2: increased glycolysis
3: decreased respiration
4: mitophagy
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