Generation of Ketone BodiesCompiled by Group 3 : Immanuelle Orchidea, Rohsi Purnama Sari, Nugroho Windu Hadi

Types of Ketone bodies

CH3-C-CH2-COO

CH3-C-CH3

=O

=O

CH3-C-CH2-COO--OH

H

acetoacetate

acetone

D-β-hydroxybutyrate

Water soluble

Types of Ketone Bodies

Acetoacetate : if not oxidized to form usable energy, used as source of two other ketone bodies

Acetone : cannot be used by brain for energy. Generated through decarboxylation of acetoacetate (enzyme : acetoacetate decarboxylase) released by breathing it off, or via urine excretion.

D-β-hydroxybutyrate : generated through the action of the enzyme D-β-hydroxybutyrate dehydrogenase on acetoacetate

Ketone bodies

Produced as “by-products” from breakdown of fatty acids in liver.

Acetoacetic acid & D-β-hydroxybutyric acid used as energy source in heart and brain

( during fasting/ low blood-glucose conditions)

Acetone = waste product= EXCRETED!!!

Purpose

Modification of acetyl coA from fat catabolism into ketone bodies, to be delivered into other peripheral tissues, then turn into CO2 and H2O by oxidation process. (Lehninger pg.213)

Other tissues : brain tissues, etc.

Regulation of Fatty Acid Oxidation & Generation of Ketone Bodies

Fatty acyl coA

Oxidation in mitochondria

Oxidation of acetyl coA in

TCA cycle

Alteration into ketone bodies

Alternating into triacylglicerol & phospholipid by

enymatic reactions in cytosol

Produced from acetyl CoA mainly in the mitochondrial matrix of hepatocytes

Scarcity of carbohydrate -> fatty acid breakdown-> obtain energy

High level acetyl coA -> pyruvate dehydrogenase complex is inhibited-> pyruvate carboxylase activated.

High level of ATP & NADH inhibit the enzyme isocitrate dehydrogenase in TCA cycle->increasing of malate.

High level of NADH & ATP -> B-oxidation Excess of acetyl coA-> rerouted to ketogenesis

Ketogenesis

Low level of blood glucose : exhaustion, fasting, sleeping, etc. -> body still needs energy -> breakdown the fatty acid into ketone bodies

Excessive of blood glucose -> unable to be stored as glycogen -> fatty acid

Synthesis of acetoacetate in liver

2 Acetyl-S-CoA acetoacetyl-S-CoA + CoA-SH

acetoacetyl-S-CoA + H2O acetoacetate + coA-SH

Acetoacetate + NADH + H+ D-β-hydroxybutyrate + NAD+

Delivered to peripheral tissues

D-β-hydroxybutyrate dehidrogenase

Hydroxymethyl-glutaryl-CoA synthase

acetoacetyl-S-CoA + H2O acetoacetate + coA-SH

CH3-C-CH2-C-S-CoA=O

=O

+ CH3-CO-S-CoA

H2OCoA-SH +

H+

Acetoacetate + acetyl CoA

HO-C-CH2

-CH2

-COO

CH2 --

C-S-CoA=O

β-hydroxy β-methylglutaryl-CoA

Hydroxymethyl-glutaryl-CoA lyase

+ CH3-CO-S-CoACH3-C-CH2-COO=O

In Peripheral Tissues

D-β-hydroxybutyrate dehidrogenase

Succynil-S-CoA + Acetoacetate succinate + acetoacetyl-S-CoA

D-β-hydroxybutyrate + NAD+ Acetoacetate + NADH + H+

3-ketoacyl-CoA transferase

NEXT

acetoacetyl-S-CoA + CoA-SH 2 Acetyl-S-CoA

tiolase

TCA CYCLE

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