Carbs and Lipid metabolism Flashcards
How does increased glucose levels cause damage
Oxidative stress
What does glutathione do
Neutralises reactive oxygen species
What is hyperglycaemia-induced superoxide production
Increased NADH/FADH2 from krebs increases proton gradient in mitochondrial membrane
This inhibits electron transfer in Electron Transport Chain
Therefore increased electron transfer to oxygen which causes SUPEROXIDE production
what does superoxide overproduction do
Inhibits GAPDH which prevents glycolysis and instead causes these 4 pathways to occur:
Polyol pathway
Hexosamine pathway
Protein Kinase C pathway
AGE pathway
Polyol pathway
glucose -> sorbitol -> fructose
Uses lots of NADPH
Protein Kinase C Pathway
DHAP converted to DAG, DAG activates PKC
Increased PKC causes more NAD(P)H oxidases, causing more reactive oxygen species leading to damage
What is methylglyoxal
Toxic by product of glycolysis
Very reactive carbonyl
How is methylglyoxal formed
By degradation of DHAP and GAP
What is AGE
Formed by methylglyoxal reacting with amine groups to form imine.
What does AGE do
Binds to receptor inducing production of reactive oxygen species and can cause changes in gene expression
What are AGE’s linked to
Long term complications for diabetes
How is methylglyoxal deactivated
By glutathione
What happens during ketoacidosis
Lowered basal insulin.
Causes:
Increased TAG hydrolysis -> Increased fatty acid levels which are catabolised to give increased Acetyl-CoA levels
Acetyl-CoA converted to ketone bodes
What is catabolism
Large -> smaller molecules
Produces energy
What is anabolism
Small molecules joint to make bigger ones