Ketone bodies

1
Ketone bodies

• M.Prasad Naidu
• MSc Medical Biochemistry,
• Ph.D.Research Scholar

2
Ketone bodies

• Normally, total body needs of energy (ATP) is met
  by various fuels .
• Carbohydrates (glucose) 70.
• Fat (fatty acids) 25.
• Proteins (Amino acids) 5.
• Ketone bodies normally negligible .
• In a normal well fed person ketone body
  concentration is only lt 1mg/dl.
• In prolonged starvation its concentration may
  increase up to 500mg/dl

3

• Adipose tissue.
• During Starvation
• epinephrine, Glucagon Hormone sensitive lipase
• Lipolysis
• Fatty acid
• Beta oxidation in Liver
• Acetyl CoA

4
TCA cycle
High NADH
Low NADH
Muscle , Myocardium
Energy production
5
KETONE BODIES- SYNTHESISKetone body synthesis is
active in 1. starvation and 2.uncontrolled
diabetes mellitus
Site of synthesis liver mitochondria

• ACETYL-COA ACETYL-COA
• Thiolase
• ACETO-ACETYL-COA
• Acetyl CoA HMG CoA synthase
• CoA
• HMG CoA

6

• HMG-COA
• CoA
• ACETO ACETIC ACID
• Dehydrogenase
• ACETONE 3-HYDROXY BUTYRATE

HMG CoA Lyase
NADH
Sponteneous
NAD
CO2
3-HYDROXY BUTYRATE
7
(No Transcript)
8
Fate and utilization
3
Succinyl coA Acetoacetate CoA Transferase
(Thiophorase)

• Fig 10.18

Utilization of Ketone bodies in Muscle ,
Myocadium for ATP production
9

• Acetoacetate is major energy source in cardiac
  muscle and renal cortex also in brain in
  starvation and diabetes

10
Ketones in Diabetes Mellitus

• In presence of insulin
• Enhanced glucose uptake by tissues
• Decreased mobilization of lipids by
  adipocytes
• In absence of insulin
• Decreased glucose uptake by tissues
• Increased mobilization of lipids by adipocytes

11
Regulation

• 1.Lipolysis of TAG
• 2. CAT-I
• 3. Acetyl co-A

12

• Ketosis does not occur in vivo unless there is an
  increase in the level of circulating free fatty
  acids that arise from lipolysis of
  triacylglycerol in adipose tissue.
• Free fatty acids are the precursors of ketone
  bodies in the liver.

13

• The liver, both in fed and in fasting conditions,
  extracts about 30 of the free fatty acids
  passing through it, so that at high
  concentrations the flux passing into the liver is
  substantial.
• Therefore, the factors regulating mobilization
  of free fatty acids from adipose tissue are
  important in controlling ketogenesis

14
(No Transcript)
15
Regulation of Ketone body synthesis
16
Disorders

• Fig 10.21

Ketonemia --- ketonuria --------
ketosis
17
THANK YOU