Ketone Bodies

Question 1

GR: Ketone bodies are an imp source of energy for peripheral tissue

Answer 1

1. They are soluble in aqueous media thus don’t need to be incorporated into lipoprotein or carried by albmin as lipid
2. They are produced by liver when acetyl CoA exceeds its oxidative capacity
3. They are used in proportion to their conc in blood by extrahepatic tissue as heart, skm & renal cortex, even brain can use them if levels rise sufficiently. They are imp in periods of fasting.

Question 2

How do the disorders of fatty acid oxidation affect the blood & ketone bodies level?

Answer 2

General picture of hypoketosis (due to dec availability of acetyl CoA) & hypoglycemia (due to inc reliance on glucosr)

Question 3

The 2 function ketone bodies are……

Answer 3

Acetoacetate & b-hydroxybutyrate

Question 4

Inc acetyl CoA activates……& inhibits……..producing……used in…….

Answer 4

Pyruvate carboxylase
Pyruvate dehydrogenase
OAA
Gluconeogenesis

Question 5

GR: Liver doesn’t use KB

Answer 5

It lacks thiophorase enzyme

Question 6

Describe regulation of ketogenesis

Answer 6

1. Substrate level regulation: during starvation cells are glucose starved & lipolysis is activated by low I/G ratio causing release FFA stimulates ketogenesis in liver. Acetyl CoA the substrate for ketogenesis is an allosteric effector of pyruvate carboxylase a gluconeogenic enzyme.
   Fatty acid oxidation causes low NAD to NADH ratio, leading to shift from OAA to malate & shift from gluconeogenesis to ketogenesis.
2. Inc glucagon cause inc transcription of mitochondrial HMG CoA synthase

Question 7

Identify organs that perform ketolysis

Answer 7

All extrahepatic tissues except those which lack mitochodria as RBCs as ketolysis occurs in mitochondria.

Question 8

Mention steps of ketolysis

Answer 8

1. 3-hydroxybutyrate converted to acetoacetate by 3-hydroxybutyrate dehydrogenase
2. Acetoacetate is provided with CoA from succinyl CoA by succinyl CoA:acetoacetate CoA transferase (thiophorase)
3. Acetoacetyl CoA is cleaved into 2 acetyl CoA by b-ketothiolase

Answer 9

1. Fluity odor of breath (acetone)
2. symptoms of acedemia as pKa of KBs is 4 thus every ketone body loses H+ while circulating in blood
3. Dehydration due to excretion of glucose & ketone bodies in urine
   Thus severe acidosis takes place

Question 10

List causes of ketosis

Answer 10

1. Diabetes mellitus
2. Starvation
3. Unbalanced diet (low CHO-high lipid)
4. Von Gierke’s disease
5. Chronic alcoholism
6. Pyruvate carboxylase deficiency
7. Glycogen storage disease type 6