Ketogenesis PDF

LIPID METABOLISM:
KETOGENESIS
Ike Dhiah R.
1
Oxidation of Fatty Acids
Objectives
• The process fatty acid transportation in the blood
• Beta oxidation pathway which leads to ATP production
• Ketone bodies are important fuels for extra hepatic tissue
• Diseases associated with impaired fatty acid oxidation
2
LIPID CLASSIFICATION
Complex
Simple Lipids Derived Lipids
Lipids
• Fats (Esters of • Phospholipids • Fatty acids
fatty acids • Glycolipids • Glycerol
with glycerols) • Lipoproteins • Steroids
• Waxes • Ketonebodies
3
Saturated chains: No double bonds
Unsaturated: Containing one or more double bonds
4
Classification of Unsaturated Fatty Acid
Monounsaturated
• One double bond
Polyunsaturated
• Two or more double bonds
Eicosanoids
• Derived from eicosa (20-carbon)
7
Productions and Actions of Prostaglandins
Trans Fatty Acids
• Saturation of fatty acids

during hydrogenation or
hardening, of natural oils in
the manufacture of margarine
• Increasing risk of
Cardiovascular disease
Physiological Properties of Fatty Acids
and Degree of Unsaturation
• Melting points (even-numbered carbon fatty acids)

increase with chain length and decrease according to
unsaturation
• TAG (3 saturated fatty acids of 12 or more carbons is
solid at body temperature), whereas if fatty acids residues
are polyunsaturated, it is liquid to below O0C
• Membrane lipids: fluid at all environmental temperatures,
more unsaturated than storage lipids
Omega-3 Fatty Acids
• Alpha-linolenic acids
(ALA): plant oils
Cardiovascular Disease
• Eicosapentaenoic
Alzheimer’s Disease
(EPA): fish oils
Rheumatoid Arthritis
• Docosahexaenoic
(DHA): fish and algal
oils
Triacylglycerols are esters of trihydric alcohol glycerol and fatty acids
15
Oxidation of Fatty
Acids: Ketogenesis
Fatty acids are transported in
the blood, activated and
transported into the matrix of
the mitochondria for breakdown
to energy
Transportation of FA
in the Blood
• Free Fatty Acids (FFA) / Unesterified Fatty Acids (UFA) /

Nonesterified Fatty Acids (NEFA)
• Longer chain FFA: Combined with albumin

• Shorter: More water soluble – unionized acid or fatty acid
anion
Transport Fatty Acids Through
Mitochondrial Membrane
• Free Fatty Acids (FFA) —>

Acyl CoA
• Acyl CoA + Carnitine —>

Acylcarnitine + CoA
• Acylcarnitine can penetrate

into inner membrane of
mitochondria
19
Beta Oxidation of Fatty Acids
• 2 carbons are cleaved from

Acyl CoA
• Palmitoyl CoA
• Acetyl CoA
20
Beta-Oxidation of Fatty Acids
Long chain acyl-CoA is cycled through reactions (2-5),
Acyl CoA being split off, each cycle by Thiolase.
2 Acetyl-CoA molecules are formed
21
Oxidation of Fatty Acids Produces
Large Quantity of ATP
Formation, Utilization, and Excretion of Ketone Bodies
23
Ketone Bodies
Fuels for tissues:
Soluble in aqueous
Produced when acetyl

coA present exceeds
oxidative capacity of liver
used in extra hepatic

tissue: skeletal and
cardiac muscle
Acetoacetate
3-hydroxybutirate
Acetone
24
Ketone Bodies
25
Transport of Ketone Bodies
26
Regulation of
Ketogenesis
27
Ketogenesis
1. Control of FFA mobilization from adipose tissues

2. The activity of carnitine palmitoyltransferase-I in liver,
which determines proportion of fatty acid that is oxidized
rather than esterified
3. Partition of acetyl-CoA between the pathway of
ketogenesis and citric acid cycle
Fatty Acid
Biosyntesis
Biosynthesis of Malonyl-CoA
After the formation of malonyl-CoA, fatty acids are formed by the fatty
acid synthase enzyme complex.
Insulin and Lipogenesis
• Acetyl-Co-A Carboxylase
• Level of intracellular cAMP:
activity
inhibits lipolysis in adipose
• Transport of Glucose into cell
tissue
• Availability of pyruvate for
• Concentration of plasma FFA
fatty acid synthesis and
– long chain acyl-coA
glycerol-3-phosphate for
(inhibitors of lipogenesis)
TAG synthesis
Nutritional State and Lipogenesis
• Lipogenesis • Lipogenesis
• Surplus glucose and • Fructose intake (instead of
intermediates (pyruvate, Glucose)
lactate,and acetyl-CoA) – • Fructose bypasses the
Fat phosphofructokinase
control point in glycolysis
• Restricted calorie intake, and floods the lipogenic
high-fat diet, insulin pathway)
deficiency
SYNTHESIS AND DEGRADATION OF FATTY ACIDS
33
• Ketoacidosis as complication
of Diabetes Mellitus
34
REFERENCES
• Rodwell VW, Bender DA, Botham KM, Kennely PJ, Weil PA.
2015. Harper’s Illustrated Biochemistry. 30th Edition. McGraw
Hill
• Crook MA. Clinical Biochemistry and Metabolic Medicine. 8th

edition.
• Lehninger. Principles of Biochemistry. 5th edition. 2008
• Frayn KN. Metabolic Regulation: A Human Perspective.3rd

edition. 2010. Wiley Blackwell
• Harvey RA. Lippincott Illustrated Biochemistry. 5th edition. 2011.

Lippincott William Wilkins
36

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LIPID METABOLISM:

• The process fatty acid transportation in the blood

• Beta oxidation pathway which leads to ATP production

• Ketone bodies are important fuels for extra hepatic tissue

• Diseases associated with impaired fatty acid oxidation

• Saturation of fatty acids

• Melting points (even-numbered carbon fatty acids)

• Free Fatty Acids (FFA) / Unesterified Fatty Acids (UFA) /

• Longer chain FFA: Combined with albumin

• Free Fatty Acids (FFA) —>

• Acyl CoA + Carnitine —>

• Acylcarnitine can penetrate

• 2 carbons are cleaved from

Fuels for tissues:

Produced when acetyl

used in extra hepatic

1. Control of FFA mobilization from adipose tissues

• Crook MA. Clinical Biochemistry and Metabolic Medicine. 8th

• Lehninger. Principles of Biochemistry. 5th edition. 2008

• Frayn KN. Metabolic Regulation: A Human Perspective.3rd

• Harvey RA. Lippincott Illustrated Biochemistry. 5th edition. 2011.

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