Molecular mechanisms, including oxidative stress and mitochondria
11 important questions on Molecular mechanisms, including oxidative stress and mitochondria
When does Cardiac ischemia occur?
Name a Cardiac reperfusion (an operation)
Most of the energy utilised by the normal heart is derived from:
It needs a lot of energy and fat = 37 kJ/g
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Which one can be only metabolised in a well-oxygenated adult heart?
- Fat
- Carbohydrate
The molecular pathway in response to ischemia/hypoxia
- Several transcription factors regulate the response to ischemia/hypoxia
- the is a physiological response to promote survival and to restore oxygen delivery
- hypoxia inducible factor 1 (HIF-1) is a transcription factor that functions as a master regulator of oxygen homeostasis
- Dimer
- HIF (HIF alpha) - regulated
- ARNT (HIF beta) - constitutive
What is the main role of HIF?
How are the HIF alpha's regulated? (Hypoxia)
The stability of HIF is regulated by the molecular oxygen sensors EGLNs and HIF1AN
Hydroxylation reaction is dependent on oxygen
normoxia: Oxygen, hydroxylation, degradation
hypoxia: No oxygen, no hydroxylation, no degradation
Normoxia: role of EGLNs and HIF1AN (6 steps)
Hypoxia (and other inhibiting conditions)
EGLNs and HIF1AN are dependent on ...(4) And are inhibited by ...(6)
- Oxygen
- Fe2+
- 2-oxoglutarate
- Ascorbate
EGLNs and HIF1AN are inhibited by
- Lack of oxygen
- Reactive oxygen species
- Fumarate
- Succinate
- Iron chelators
- Co2+
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