Lipid Metabolism II (Lecture 2 - Exam 3) Flashcards
Where are ketones synthesized?
LIVER exclusively; within the mitochondria
What intermediates are used to make ketones?
Pyruvate
AAs
FAs
How are ketones transported in the body?
They are water-soluble, so they do not require a transport protein
What are the physiological conditions that induce ketone synthesis?
During a fast, the liver is flooded with FFAs mobilized from adipose tissue. Beta-oxidation results in increased acetyl-CoA in liver, which:
–Inhibits pyruvate dehydrogenase (glycolysis)
–Activates pyruvate carboxylate producing OAA (gluconeogenesis), which will be reduced by NADH forming malate, which now means it cannot enter the Kreb’s Cycle, resulting in a build-up of acetyl CoA
Why are ketone bodies an important source of energy for the peripheral tissues?
1) Soluble in aqueous solution
2) are produced in the liver during periods when the amount of acetyl-CoA present exceeds the oxidative capacity of the liver
3) used in proportion to their concentration in the blood by extrahepatic tissues, such as SM, cardiac muscle, etc.
(TRUE/FALSE)
The brain can use ketone bodies.
TRUE
What are the steps in ketone synthesis?
1) THIOLASE converts 2 acetyl CoA to acetoacetyl CoA
2) HMG CoA SYNTHASE catalyzes the formation of HMG CoA from acetoacetyl CoA and acetyl CoA
3) HMG CoA lyase cleaves CoA from HMG CoA forming acetoacetate
4) Acetoacetate can leave the hepatocyte and enter circulation, OR be converted to 3-hydrooxybutyrate (requires NADH), OR acetone
What are the steps in ketone oxidation?
3-hydroxybutyrate exits the liver and enters peripheral tissue (muscle)
1) 3-HYDROXYBUTYRATE DEHYDROGENASE converts 3-hydroxybutyrate to acetoacetate and NADH is formed.
2) THIOPHORASE forms acetoacetyl CoA from acetoacetate and succinyl-CoA
3) THIOLASE converts acetoacetyl CoA to 2 acetyl CoA (with the addition of another CoA)
4) 2 acetyl CoA enter the Kreb’s Cycle to generate ATP
(TRUE/FALSE)
3-hydroxybutyrate needs a binding protein to circulate within the blood.
FALSE
It does NOT
What are the enzymes involved in ketone synthesis?
Thiolase
HMG CoA Synthase
HMG CoA lyase
How do cells utilize ketones?
In order to utilize ketones, cells MUST have MITOCHONDRIA and be able to use the Kreb’s Cycle to produce ATP.
Example: RBCs are dependent on gluconeogenesis OR the Cori Cycle during this time
(TRUE/FALSE)
Hepatocytes can utilize ketones.
FALSE.
They CANNOT because they do NOT express the enzyme, THIOPHORASE. So the liver is not able to metabolize ketones, only peripheral tissues that has this enzymes is able to actually use ketones.
Why is it important that the liver cannot use ketones?
Because it prevents the liver from using all the ketones that it has produced.
How does diabetic ketoacidosis occur and what are the potential complications?
DKA occurs when the rate of formation of ketone bodies is greater than the rate of their use, their levels begin to rise in the blood and eventually in the urine. Most often it is seen in uncontrolled/undiagnosed T1DM. The elevation of the ketone body concentation,
