M.Prasad NaiduMSc Medical Biochemistry,

Ph.D.Research Scholar

Ketone bodiesNormally, total body needs of energy (ATP) is

met by various fuels . 1.Carbohydrates (glucose) 70%.2.Fat (fatty acids) 25%. 3.Proteins (Amino acids) 5%. 4.Ketone bodies normally negligible %.

In a normal well fed person ketone body concentration is only < 1mg/dl.In prolonged starvation its concentration may increase up to 500mg/dl

Adipose tissue. During Starvation

epinephrine, Glucagon Hormone sensitive lipase

Lipolysis

Fatty acid

Beta oxidation in Liver

Acetyl CoA

Low NADH

High NADH TCA cycle

Energy productionMuscle , Myocardium

KETONE BODIES- SYNTHESISKetone body synthesis is active in 1. starvation and 2.uncontrolled diabetes mellitus

ACETYL-COA + ACETYL-COA Thiolase

ACETO-ACETYL-COA Acetyl CoA HMG CoA synthase

CoA

HMG CoA

Site of synthesis liver mitochondria

HMG-COA

CoA ACETO ACETIC ACID

Dehydrogenase

ACETONE 3-HYDROXY BUTYRATE

HMG CoA Lyase

CO2

NADH

NAD+

3-HYDROXY BUTYRATE

Sponteneous

Fate and utilization Fig 10.18

3

Utilization of Ketone bodies in Muscle , Myocadium for ATP production

Succinyl coA – Acetoacetate CoA Transferase (Thiophorase)

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

10

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

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

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.

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

Regulation of Ketone body synthesis

Disorders Fig 10.21

Ketonemia --- ketonuria -------- ketosis

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