Metabolism: Fatty Acids & Ketones Flashcards
What is the function of HSTL?
HSTL = hormone sensitive TAG lipase
- breaks down TAG into glycerol and FFAs
What is the function of perilipin?
perilipin (LDAP) - lipid droplet associated protein
- required for HSTL mobilization and activation
What are the sources of TAG?
- glucose => glycerol
- dietary lipids => chylomicrons
- TAG from the liver
What are the activators of HSTL?
- epinephrine (cAMP => phosphorylation)
- ACTH
- thyroid hormones and adrenal corticol hormones (not required)
What are inhibitors of HSTL?
- insulin
- prostaglandins
What are the fates of FAs released by lipolysis?
- transported in circulation via association with albumin
- carried to muscle, liver, etc.
- used in beta-oxidation and energy production
- used in TCA or to make ketone bodies
What are the fates of glycerol released by lipolysis?
- transported to liver and kidney
- used in gluconeogenesis after conversion to glycerol-3-phosphate
What does FA release inhibit?
- inhibition of fatty acid synthesis (because you need to use up TAG not store it)
- inhibition of glycolysis (because you need to generate energy, not use it up)
What does FA release activate?
- ketone body formation
- gluconeogenesis
How does FA degradation inhibit glycolysis?
- generates lots of ATP
- ATP inhibits PFK1
What is the major energy producing pathway in the body?
beta oxidation of FA
Which organs mainly use fatty acids?
liver
kidney
heart
musclee
Which organs cannot use fatty acids?
brain, CNS
RBCs
adrenal medulla
lens
How much ATP does palmitate yield?
1 palmitate = 8 aCoA + 7 FADH2 + 7 NADH
106 ATP
What is the function of carnitine?
transport of FAs into the mitochondrial matrix for beta oxidation
Inhibition of carnitine transport can lead to what?
- inhibit FA oxidation
- decreased ATP production
Describe the mechanism of carnitine.
- CPT1 acts on fatty acyl-CoA and carnitine to produce acyl-carnitine
NOTE: fatty acyl-CoA are outside the mitochondrial membrane and carnitine is on the inside of the mitochondria - CPT1 activity transfers the acyl group to be carried by carnitine
- translocase enzyme brings acyl-carnitine inside the mitochondrial matrix
- CPT2 transfers acyl to CoA to regenerate carnitine (sent out of the matrix) and acyl-CoA
- acyl-CoA is then used for beta oxidation
At which point in lipid metabolism does malonyl-CoA act upon?
malonyl-CoA inhibits CPT1
prevents attachment of acyl group to carnitine and prevents transport into mito matrix
How does malonyl-CoA affect lipid metabolism?
- increased = promotes biosynthesis, inhibits beta oxidation (because you have lots of energy you need to store)
- decreased = promotes beta oxidation (because you don’t have enough energy)
How does SIDS relate to lipid metabolism?
- deficiency in FA-CoA dehydrogenase enzyme
- prevents beta-oxidation
List examples of ketone bodies.
acetone
acetoacetate
beta-hydroxybutyrate
Describe the function of HMG-CoA Synthase and where it is active.
- only active in the liver
- eventually forms acetoacetate, which can further derivate to form acetone and beta-hydroxybutyrate
What is unique about ketone bodies in the liver?
- ketone bodies are ONLY synthesized in the liver
- however, the liver can NOT utilize them for energy because it lacks succinyl-CoA transferase (thiophorase)
What is the function of succinyl-CoA transferase?
converts ketone bodies to acetyl-CoA for use in energy production
