Objectives
- Know the fuels utilised by the heart
- be familiar with the pathways generating ATP
- Be familiar with the switching of fuels in various physiological and disease states
- be familiar with some of the regulatory points involved in fuel switching
- be familiar with the cardio proctective role of exercise and AMPK
heart uses 3.5-5 kg atp per day pumps ~10 tons of blood
can use all fuels likes fatty acids
90% of energy in fasting heart produced by mitochondrial respiration
myocardial cells are packed with mitochondia
energy use
carbo breakdown path and
First 20 mins or so he is reviewing cellular respiration
Heart fuel use
all carbs fetal, low pO2, neonatal
50/50: hypoxia, hypertrophy, exercise
fuel utilisation is effected by substrate avilability workload hormones etc
Fuel intake/uptake
Glucose
GLUT 4 insulin dependant i think GLUT 1
fatty acids
CD36 FATP6 into cell transportser
fatty acyl coa fed state: acetyl CoA triggers acc makes malonyl CoA which vlocks CPT-1,2 which is needed for fatty transport
fasting state no malonyl coa
fasting and fed state has different
The level of oxygen changes fuel usage
Ischaemia PDH act to shut off glycolysis when there is alot of acetyl coa
| state | |
|---|---|
| biabetes | more fa oxidation less carbohydrate |
| hypertrophied heart | less fa oxidation more glycolysis |
| ischaemic heart | far less oxidative metabolism more glycolysis transiently |
| hypoxic | less oxidative metabolism more glycolysis |
| reperfused | more fa oxidation less carb oxidation normal glycolysis |
Type 2 diabetes
glut 4 doesnt respond less glucose metabolism
more fatty acid more ketones
more LCFA coa blocks glycolysis
Ischaemia
less atp more amp amp kinase activated by it amp kinase down regualtes acetyl coa carboxylase which means less malonyl coa
less malonyl coa means more CPT ehich is more acyl carnitine carrier this is more beta ox
more beta ox means moa acetyl coa means ledd pydruvate transported into mitochondria pyruvate oxidation
what revs up glycolysis in hypoxia?
HIF1a
HIF1a upregulates glut1 PFK LDH and reduces FA oxidation by teducing PPARa signalling
normoxia leads to oxidation of HIF1a and eventrual destruction
Zonal hypoxia
different areas have different ox levels
Exercise is known as cardioprotective
- improves cardiovascula
- improve insulin sensitivity
- exercise activates AMPK
- activated AMPk has multiple benefitical effects