Ketone Bodies

Question 1

Ketogenesis

Answer 1

Formation of ketones in the liver.
FFA –> acetyl-CoA –> ketones

Question 2

Ketone bodies

Answer 2

Small, water soluble fatty acids

1. Acetoacetate
2. beta-hydroxybutyrate
3. Acetone

Question 3

Acetone

Answer 3

Metabolically inactive

Spontaneously created from acetoacetate when ketone body levels are very high

Question 4

Where does ketogenesis occur?

Answer 4

Liver

Question 5

When are ketones synthesized?

Answer 5

In periods of Glucose deficiency such as prolonged starvation, diabetes mellitus, carbohydrate restriction through diet

Question 6

Steps of Ketogenesis

Answer 6

1. Depletion of carbohydrates, decrease in glucose
2. Liver is undergoing gluconeogenesis, so there is no oxaloacetate present to put acetyl-CoA into TCA and ETC.
3. Acetyl-CoA is used for ketogenesis instead. 2 acetyl-CoA for acetoacetyl-CoA. Then another acetyl-CoA added to form HMG-CoA.
4. HMG-CoA degraded into acetoacetate + acetyl-CoA
5. When NADH is high (when beta-oxidation is high), acetoacetate can form beta-hydroxybutyrate

Question 7

Ketone body transport

Answer 7

Both acetoacetate and beta-hydroxybutyrate are soluble and can cross the blood-brain and placental barrier.

Question 8

Ketone bodies as fuel

Answer 8

Used by all aerobic tissues except the liver.

Extremely important for the brain, and fetus during times of starvation. Next prioritized use in physiologically significant muscles (heart, diaphragm, smooth muscle of the digestive tract, myometrial smooth muscle)

Question 9

Why are ketone bodies not used in RBCs?

Answer 9

RBCs do not have mitochondria

Question 10

What is the rate limiting step of ketogenesis? What inhibits and promotes this step?

Answer 10

Acetoacetyl-CoA +Acetyl-CoA –> HMG-CoA

Inhibited by insulin (glucose)

Promoted by glucagon

Question 11

Fatty Acid vs. Ketone bodies
Can they be used in the brain

Answer 11

FFA cannot be transported without albumin. FFA-albumin cannot pass the blood brain barrier. They are hydrophobic and bulky.

Ketone bodies are small, soluble and can pass through the blood brain barrier

Question 12

Ketone dipsticks

Answer 12

Urine dipsticks will only detect acetoacetate and not beta-hydroxybutyrate. So quick results but they underestimate the true ketone levels

Question 13

Ketone bodies once inside the destination tissues

Answer 13

beta-hydroxybutyrate and acetoacetate broken back down into acetyl-CoA which combines with oxaloacetate to go into the TCA and ETC to make ATP .

Oxaloacetate present because only liver really undergoes gluconeogenesis

Reduces pressure to undergo the costly process of gluconeogenesis.

Question 14

Negative effects of ketones

Answer 14

Acetoacetate and beta-hydroxybutyrate are naturally acidic, donating H ions to blood. Causes an increase in H, decrease in pH and HCO3-, increase in AG = Results in ketoacidosis= metabolic acidosis. Need respiratory compensation to recover levels.

Acetoacetate will spontaneously breakdown into acetone when levels are high. This is a highly volatile ketone, has a sweet smell (breath and urine)

Question 15

Ketoacidosis in diabetics

Answer 15

15-20 mM ketones in blood

not producing insulin, so producing more and more ketone bodies