W5 Energy II Flashcards
In krebs - for each glucose
6 NADH + 2 NADH
2 FADH2
2 GTP
4 CO2 + 2 CO2
Citric acid cycle key facts
Takes place in the mitochondrial matrix
In the presence of oxygen, pyruvate is converted to acetyl CoA (2C) and enters the citric acid cycle
Acetyl CoA reacts with Oxaloacetic acid (4C) to form citrate (6C)
Citrate undergoes a series of reactions resulting in the loss of 2CO2
Three molecules of NADH and one FADH2 are formed per cycle
One GTP molecule is formed
ATP is not produced in the citric acid cycle
What regulates entry into the citric acid cycle?
Formation of acetyl CoA from pyruvate is irreversible (Pyruvate dehydrogenase) (Inhibited by NADH + acetyl CoA) (Phosphorylation reduces activity)
This commits the glucose carbon skeleton to either oxidation to CO2 and energy production or Fatty Acid synthesis
Muscle regulation of citric cycle
Pyruvate dehydrogenase is activated again via the action of a phosphatase – this enzyme is stimulated by Ca2+ (facilitate generation of ATP)
Liver regulation of citric cycle
In liver adrenalin increases calcium through the activation of a adrenergic receptors and IP3
In liver and adipose tissue, insulin (which signifies the feed state) stimulates the phosphatase (activates dehydrogenase thus increase in [acetyl CoA]) which funnels glucose to fatty acid synthesis
Inhibition of isocitrate dehydrogenase and keto gluterate dehydrogenase
Leads to build up of citrate
Citrate is transported out of the mitochondria where it inhibits PFK which stops glycolysis. The citrate will also act as a source of acetyl CoA for FA synthesis
Citric acid cycle full
Pyruvate into acetyl CoA (2C) by pyruvate dehydrogenase
Stim = ADP + pyruvate
Inhibit = NADH, ATP + acetyl CoA
Acetyl CoA into citrate (6C) by citrate synthase
Inhibit = citrate
Isocitrate into AKG (5C) by isocitrate dehydrogenase also producing NADH + CO2
Stim = ADP
Inhibit = NADH + ATP
AKG into succinyl CoA (4C) by AKG dehydrogenase also producing NADH + CO2
Inhibit = NADH, ATP + succinyl CoA
Succinyl CoA into succinate also producing GTP
Succinate into fumarate also producing FADH2
Fumarate into malate
Malate into oxaloacetate also producing NADH
Beriberi
Is a deficiency in thiamine (Vit B1)
Common where rice is a staple
Characterised by cardiac and neurological symptoms
Thiamine is a prosthetic group for pyruvate and a-ketogluterate dehydrogenase
Neurological disorders are common as glucose is the primary source of energy
Suffer in processes requiring ATP
Electron transport summary
Electron transport is coupled to ATP synthesis
It needs 3 protons to make one ATP
As one proton is consumed to transport ATP out of the matrix four protons in total are needed to generate one ATP
Electron transport full
NADH + FADH2 taken up by protein complexes
Oxidation reactions occur releasing electrons
Electrons passed from one complex (cytochromes) to another while releasing energy due to redox reactions
e- move from high energy state to a low energy state
Energy released from e- used to generate electrochemical gradient as H+ pumped into IM space
Forms a pH gradient transmembrane potential (proton motive force)
So generating potential to make energy
H+ from IM to matrix through stalked granules to generate ATP
NADH/FADH2 facts
NADH forms 3ATP
FADH2 forms 2ATP
10 H+ pumped out for every NADH
6 H+ pumped out for every FADH2
Mitochondria and heat generation in the new born
Brown fat generates less NADH + FADH2
Don’t have shiver reflex so uncouple e- from ATP synthesis and proton gradient
Through uncoupling protein as now it is just the route for entry of H+
So short circuits ATP synthase
So heat generated
OXPHOS Diseases
Common degenerative diseases
Caused by mutations in genes encoding proteins of ETC
Lead to a number of symptoms, including fatigue, epilepsy, dementia
Dependent on the mutation, symptoms may be evident near birth to early adulthood
Metabolic consequence can be congenital lactic acidosis
