Organ specialisation & integration of metabolic pathways for fuel & energy

Lecture 8

What are the fuel specialisations of the brain?

requires steady supply of glucose

Up to 50% of requirement can be met by ketone bodies if needed.

What are the fuel specialisations of muscle?

major fuels - glucose from glycogen, fatty acids & ketone bodies

Cannot export glucose or do gluconeogenesis

heart - relies on aerobic metabolism

favoured fuel during rest is fatty acids

under stress it draws on limited glycogen stores

What are the fuel specialisations of the liver?

acts as a buffer of blood glucose

can synthesise/break down TAG

makes but cannot use ketone bodies as does not have key enzyme for their breakdown

dietary proteins degraded to amino acids

skeletal muscle used as energy reserve during a fast

*NB - TAG should not be stored in the liver in healthy individuals

What are the fuel specialisations of adipose tissue?

stores & releases fatty acids

releases hormones like AMPK that regulate metabolism

does not contain glycerol kinase - FFA exported if glucose uptake is low

uses GLUT4 transporters, so insulin directly controls glucose uptake.

What are the fuel specialisations of the pancreas?

blood glucose level detected by glucokinase

Glucose-6-phosphate goes to oxidative phosphorylation

linked to insulin synthesis & release

What are the fuel specialisations of the kidneys?

dispose of urea

maintains blood pH

carries out gluconeogenesis

How is dietary TAG digested?

emulsified by bile acids in the small intestine into micelles

pancreas releases lipase which hydrolyses TAG at the micelle surface, forming fatty acids & monoacylglycerols.

Fatty acids & monoacylglycerols are absorbed into the brush border of the intestine.

Converted back into TAG & packaged into chylomicrons

chylomicrons are secreted into the lymph system & enter the blood at thoracic duct.

How is TAG removed from the blood?

Lipoprotein lipase binds to very low density lipoprotein (VLDL) & chylomicrons

LPL hydrolyses TAG

Fatty acids released into cells

Adipose makes TAG & muscle cells oxidise the fatty acids.

How is lipolysis controlled in adipose tissue?

Glucagon, noradrenaline & adrenaline raise [cAMP]

Insulin breaks down cAMP via phosphodiesterase enzyme

TAG lipase phosphorylated by PKA.

Adipose triglyceride lipase (ATGL) antagonised by insulin also.

NB - fasting, prolonged exercise & stress raise blood fatty acid content

What mechanism allows the use of glycolysis for longer when using anaerobic metabolism in exercise?

AMP formed by adenylate kinase

AMP deaminated to inosine monophosphate

glycogenolysis stimulated

IMP degraded to adenosine, stimulating vasodilation