Lecture - CVS (Cardiac Metabolism) Flashcards
Fuels for the heart
- What fuels can the heart use? List them
- Myocardium is highly ______ and has a preference for what?
- More than 90% of the energy is produced by what for the heart?
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What can you see in this histology slide?
Heart fuel use:
For each of these, explain whether you use more carbs or lipids and why that would make sense in the conditions:
- Fetal
- Neonatal
- Exercise, hypoxia, hypertrphy, failure
- why is exercise cardio-protective? - Adult
- Fasting, diabetes
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Fuel Utilisation is determined by what four things?
Why?
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Energy use for contraction:
Explain the ATP producing pathways for the heart
For carbohydrates:
You have the glycogen or the glucose going into glycolysis and forming pyruvate. If not enough O2 then it forms lactate. But if there is enough oxygen then the pyruvate will form Acetyl-CoA and that will go into the Kreb Cycle to then generate electrons in the form of hydride ions in the Electron Transprort Chain
Amino acids:
Will either pyruvate (which will go into the Kreb Cycle) or it will go straight into the Kreb Cycle by forming an intermediate
Fatty acids:
These will be turned into Acyl CoA which, through the carnitine carrier, will enter the intramitochondrial space and through the Beta-Oxidation spiral form many Acetyl-CoA and they will enter the Kreb cycle to also produce electrons in the form of hydride ions and then go through the ETC to form ATP
Uptake of fuels:
Explain how glucose and fatty acids are taken up by the cells
Glucose uptake:
So insulin will promote the GLUT-4 channels to embed in the cell membrane (so they are insulin-responsive transporters). These will allow the glucose to enter the cell. The glucose will enter, form pyruvate (through glycolysis) and then through pyruvate-dehydrogenase will enter the mitochondria to go throught the Kreb Cycle to form the NAHD or FADH2 and then these will go to the ETC and form ATP. Another type of glucose transporter is GLUT-1 and this is not insulin-responsive - it is sensitive to the amount of glucose instead.
Fatty acid uptake:
The VLDL (and chylomicrons, I think) will get their TAGs hydrolysed by the lipoprotein lipase to form FA and glycerols. Both the FA and the glycerol will enter the cell. The FA will get turned into Fatty Acyl CoA in the cytoplasm and that will go through the carnitine shuttle to enter the mitochondria and go through beta oxidation to form acetyl coA and then the NADH + FADH2 from that will enter the ETC. The FA can enter not only by the VLDL or chylomicrons but also through albumin-bound Long Chain Fatty Acids. These are released by adipose tissue etc by hormone sensitive lipase (by glucagon in fast state, I think) and this will liberate FA and some of these attach to albumin to be transported - also enter the cell to be aceylated into Fatty acyl CoA etc.
Explain the thing between the FA metabolism and Carb metabolism - why can’t both happen?
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Substrate use with disease:
What happens to the FA oxidation, glycolysis, and oxidative metabolsim with these disease:
- diabetes
- hypertrophied heart
- ischemic heart (flow dependent)
- hypoxic heart
- reperfused heart
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Fatty Acid Metabolism
How does this change with ischaemia?
lower levels of ATP and higher levels of AMP (which upregualtes AMP kinase) - when AMP kinase (enzyme) is upregualted, there is a downregualtion of ACC and then less malonyl coA so more beta oxidation going on so one reason that in ishcameic heart, you increase betaa oxidation but that’s a pproblem bc with more beta oxi, there is more reactive oxygen species generated but there is less oxygen around and less blood around to get rid of the oxygen species so ends up casuing more damage.
What happens with hypoxia and the subsrate use stuff?
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What happens to the cardiac metabolism in type 2 diabetic heart?
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What’s the metabolsim in the ischaemic heart?
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Why is exercise cardioprotective?
Because during exercise, the heart is training itself to live under ischaemic conditions.You also decrease FA synthesis, increase fat oxidation, decrease lipogenic gene expression and decrease cholesterol synthesis
