L5- Energy and redox signalling Flashcards
What is energy state?
The balance between production and use of energy sources.
Why is ATP a poor indicator of energy state?
Because homeostatic mechanisms match ATP availability to ATP utilisation so the concentration of ATP may not actually change.
What are the ways in which energy is generated?
- Anaerobic respiration (glycolysis, beta oxidation) to produce acetyl co-A
- Acetyl co-A progressively dehydrogenated in TCA cycle. H+ transferred to NAD and FAD to produce NADH and FADH2 and CO2 remains.
- NADH and FADH2 oxidated in the electron transport chain in oxidative phosphorylation. H+ and e- released to reduce oxygen to water and produce ATP.
What are the end products of glycolysis?
2ATP (relatively inefficient)
Pyruvate
2NADH
What are the steps in glycolysis?
Glucose Hexokinase Phosphofructokinase Glyceraldehyde-3-phosphate dehydrogenase Phospholgycerate kinase Pyruvate kinase Pyruvate- either goes to Mt or converted to lactate by lactate dehydrogenase in anaerobic conditions
What generates acetyl co-A?
Pyruvate converted to acetyl-coA by pyruvate dehydrogenase
Produced by beta oxidation
How is pyruvate dehydrogenase regulated?
It is inactive in the phosphorylated form and active when unphosphorylated.
Regulated by PDH kinase and PDH phosphatase.
What stimulates and inhibits PDH kinase and phosphatase?
PDH kinase stimulators: Acetyl coA, NADH, ATP
PDH kinase inhibitors: Pyruvate, NAD+, ADP, Ca2+
PDH phosphatase stimulators: Ca2+, Mg2+
Why do Ca2+ and Mg2+ stimulate PDH phosphatase?
Increases in cellular Ca2+ means Ca2+ needs to exit the cell. ATP is needed for this.
Mg2+ normally binds to ATP so if there is less ATP then there is more free Mg2+.
What happens in oxidative phosphorylation?
NADH and FADH2 produced in the Krebs cycle are reoxidised.
This produces e- and H+ which are extruded across the inner mitochondrial membrane.
The H+ gradient drives the F1F0 ATP synthase pump.
31 ATP produced per glucose
What is the adenylate kinase reaction?
[ADP] + [ADP] —> [ATP] + [AMP]
Enzyme transfers Pi from ADP to another ADP
What is the AMP to ATP ratio useful for?
It is a sensitive measure of energy state
AMP:ATP proportional to (ADP:ATP)^2
Why is the adenylate kinase reaction useful?
Allows [ATP] to be preserved when utilisation is high or production is low
What is the role of phosphocreatine?
[ATP] + [Cr] [PCr] + [ADP] + [H+]
ADP/ATP are large and immobile so PCr acts as a transport medium as it is a small freely diffusible molecule (to sites of utilisation).
Can act as an ATP reserve to keep it constant
What are the most sensitive measures of energy status?
[AMP] : [ATP] which is proportional to (ADP:ATP)^2
AMPK
What is AMPK?
AMP activated kinase
Plays a role in whole body and cellular homeostasis
Slows energy usage but increases production
How is AMPK regulated?
It is constitutively active but its activity is increased by phosphorylation by AMPK kinase.
AMPK kinase is activated by AMP
AMP also directly activates the phosphorylated AMPK
AMP inhibits AMPK phosphatase
What switches on AMPK?
Metabolic stresses such as heat shock, hypoxia, ischaemia and glucose deprivation.
Causes an increased AMP to ATP ratio
Causes an increase in AMPK
Causes an increase in catabolic (ATP producing) pathways
What roles does AMPK play in whole body energy homeostasis?
Fasting state, exercise and adiponectin hormone causes increases in AMPK in brain, liver, muscle and adipose tissue.
What are impacts of AMPK increases on the brain?
Increased appetite and food intake
What are the impacts of AMPK increases on the liver?
Decreased synthesis of fatty acids and cholesterol
Decreased glycogenesis
What are the impacts of AMPK on the adipose tissue?
Decreased synthesis of fatty acids
What are the impacts of AMPK on muscle?
Catabolic
Increased FA uptake and beta oxidation
Increased glucose uptake
Decreased protein synthesis
