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LIPID METABOLISM

Sri Suciati Ningsih


FK UHAMKA

11 Maret 2020
1. Understanding the process of lipid digestion, absorption, and
transport in the human body.
2. Understanding synthesis of fatty acid and triglycerides.
3. Understanding the mechanism of storage and release of lipids in
adipose tissue.
4. Understanding the fatty acid oxidation process
5. Understanding the synthesis process of ketone bodies and their
functions
6. Understanding cholesterol absorption, synthesis and
metabolism.
7. Understanding eicosanoid metabolism.
8. Understanding the integration of lipid and carbohydrate
metabolism.

Learning Objectives
Most of the lipids found in the body fall into the categories
of fatty acids and triacylglycerols; glycerophospholipids
and sphingolipids;
eicosanoids; cholesterol, bile salts, and steroid hormones;
and fat-soluble vitamins.
LIPID STRUCTURE
Digesti dan absorpsi
lipid
Apoprotein
B-48

SYNTHESIS OF
CHYLOMICRON
S
Transport of lipid
• The de novo synthesis of fatty acids from acetyl-CoA
occurs in the cytosol on the fatty acid synthase complex.

FATTY ACID AND


TRIACYLGLYCERO
L
SYNTHESIS
VLDL
STORAGE OF TRIACYLGLYCEROLS
IN
ADIPOSE TISSUE
RELEASE OF FATTY ACIDS FROM
ADIPOSE
Fatty acids are transported in the blood complexed with
albumin, taken up by various tissues, and oxidized for
energy.
In the liver, fatty acids are converted to ketone bodies, and
glycerol is converted to glucose. These fuels serve as
energy sources for other tissues.
FATTY ACID OXIDATION

In the cytosol of the cell, long-chain fatty acids are


activated by ATP and coenzyme A, and fatty
acyl-CoA is formed

Fatty acyl-CoA from the cytosol reacts with


carnitine in the outer mitochondrial membrane,
forming fatty acylcarnitine. The enzyme is
carnitine acyltransferase I (CAT I), which is also
called carnitine palmitoyltransferase I (CPT I).
Fatty acylcarnitine passes to the inner membrane,
where it re-forms to fatty acyl-CoA, which enters
the matrix. The second enzyme is
carnitine acyltransferase II (CAT II).
Cont…
KETONE BODY
SYNTHESIS AND
UTILIZATION
• The synthesis of ketone bodies occurs
in liver mitochondria when fatty
acids are in high concentration in the
blood (during fasting, starvation, or
as a result of a high-fat diet).
• The ketone bodies, acetoacetate and β-
hydroxybutyrate, serve as a source of fuel.
They are synthesized mainly in liver
mitochondria whenever fatty acid levels are
high in the blood.
• Ketone bodies are used as fuels by tissues
such as muscle and kidney. During
starvation (after about 3 to 5 days of
fasting), the brain also oxidizes ketone

bodies
Cholesterol Absorption, Synthesis,
Metabolism, and Fate
• Cholesterol,which is transported in the blood in lipoproteins because of its
absolute insolubility in water, serves as a stabilizing component of cell
membranes and as a precursor of the bile salts and steroid hormones.
• The precursor for cholesterol synthesis is acetyl coenzyme A (acetyl-CoA),
which can be produced from glucose, fatty acids, or amino acids. The
adrenal cortex and the gonads also synthesize cholesterol in significant
amounts and use it as a precursor for steroid hormone synthesis.
CHOLESTEROL
SYNTHESIS
• Cholesterol is an alicyclic compound
whose basic structure includes the
perhydrocyclopentanophenanthrene
nucleus containing four fused rings.

Stage 1: Synthesis of Mevalonate from Acetyl-CoA


CHOLESTEROL
SYNTHESIS
Stage 2: Conversion of Mevalonate to Two
Activated Isoprenes
CHOLESTEROL
SYNTHESIS Stage 3: Condensation of
Six Activated Five-Carbon
Isoprenes to Form the
30- Carbon Squalene
CHOLESTEROL
SYNTHESIS
Stage 4: Conversion of Squalene to the Four-Ring
Steroid Nucleus

The liver packages some of cholesterol into the hollow core of


lipoproteins, primarily VLDL. VLDL is secreted from the
hepatocyte into the blood and transports to the tissues that
require greater amounts of cholesterol. These tissues then
use the cholesterol for the synthesis of membranes, for the
formation of steroid hormones, and for the biosynthesis of
vitamin D.
The hepatic cholesterol pool serves as a source of cholesterol
for the synthesis of the relatively hydrophilic bile acids and
their salts
Cholesterol Absorption, Synthesis,
Metabolism, and Fate
Cholesterol transport and
metabolism
• Almost all mammalian cells are capable of producing cholesterol. Most of
the biosynthesis of cholesterol occurs within liver cells, although the gut,
the adrenal cortex, and the gonads (as well as the placenta in pregnant
women) also produce significant quantities of the sterol.
• The ring structure of cholesterol cannot be degraded in the body. The bile
salts in the feces are the major form in which the steroid nucleus is
excreted.
• The (prostaglandins, thromboxanes, and
eicosanoids
leukotrienes) are synthesized from polyunsaturated fatty
acids (e.g., arachidonic acid). These fatty acids are released from
membrane phospholipids by phospholipase A2, which is inhibited by
glucocorticoids and other steroidal anti-inflammatory agents.
• Eicosanoids participate in many processes in the body, particularly
the inflammatory response that occurs after infection or injury
(can produce symptoms such as pain, swelling, and fever)
• Eicosanoids act by binding to specific membrane receptors, which,
depending on the eicosanoid, alter either protein kinase A activity
or calcium levels within the target cells.

Metabolism of the
Eicosanoids
Integration of Carbohydrate and Lipid Metabolism
Integration of Carbohydrate and Lipid Metabolism
• Lieberman MA and Ricer R. Biochemistry, Molecular
Biology, and Genetics 6th ed. 2014. Lippincott Williams
& Wilkins, a Wolters Kluwer business.
• Chatterjea MN. Shinde R. Textbook of Medical
Biochemistry. 2012. New Delhi. Jaypee Brothers Medical
Publisher.

References
Thank you

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