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HIF-1 - Coggle Diagram
HIF-1
Normoxia
Prolyl Hydroxylases add molecular oxygen and iron to add hydroxyl groups to specific proline amino acids on HIF-1A
The tumour suppressor protein pVHL recognises and binds to the hydroxylated HIF-1A
pVHL recruits a E3 ubiquitin ligase complex that covers the HIF-1A in ubiquitin tags, sending it to the 26S proteasome to be destroyed
HIF-1A never reaches nucleus so target genes remain off
Hypoxia
PHDs require molecular oxygen to function and so are inactive meaning HIF-1A is not hydroxylated
pVHL cannot bind to unhydroxylated HIF-1A meaning the HIF-1A rapidly accumulates in the cytoplasm
HIF-1A enters the nucleus where it binds to its stable partner HIF1-B
Also binds to co-activators like p300
HIF-1 complex binds to Hypoxia Response Elements in the DNA to turn on dozens of genes
VEGFA
Regulator of angiogenesis, causes higher blood and oxygen supply
EPO
Signals to the bone marrow to produce more RBCs increasing blood oxygen-carrying capacity
SLC2A1 (GLUT1) and HK1/2 (Hexokinase)
GLUT1 upregulation promotes more glucose transport
Hexokinases break the glucose down
LDHA and PDK1
PDK1 shuts down fuel entry into mitochondria, preventing ROS build up
LDHA then converts leftover pyruvate into lactate, maintaining anaerobic respiration