CHEM123LEC: BIOCHEMISTRY FOR MEDICAL LABORATORY SCIENCE

WEEK 15: LIPID METABOLISM

1st SEMESTER l S.Y. 2022-2023 TRANSCRIBE BY: WILLIE P. LARON JR.
LECTURER: MR. MANIMAR DRUSELLE OPERIO

• Bile, monoacylglycerols, and free fatty acids form

MAIN TOPIC
micelles.
SUB-TOPIC • Hydrophobic tails inside, hydrophilic heads outside.
SUB-SUBTOPIC
Unit Expected Outcome
At the end of the session, the students are expected to:
1. Discuss Summarily the Kreb’s Cycle
2. Inculcate importance of citric acid cycle in different
biochemical reactions in the body
DIGESTION AND ABSORPTION
❑ Digestion
• 98% of dietary lipids are triacylglycerols Intestinal Cells
• Sites of triacylglycerol digestion • Chyme in small intestine triggers hormone
o Stomach cholecystokinin.
o Small intestine • Micelles are absorbed by intestinal cells.
o Intestinal cells ➔ They are small enough to pass through.
o Lymphatic system
• Free fatty acids and monoacylglycerols are
o Bloodstream
reassembled into TAGs.
Mouth • TAGs are combined with membrane lipids and
• Triacylglycerols are not soluble in water. water-soluble proteins to form chylomicrons
• Salivary enzymes are water-based. • Chylomicrons are lipoproteins that transports TAGs
• They cannot digest lipids. from intestinal cells, via the lymphatic system, to the
bloodstream.
Stomach
• Mostly physical digestion
• Stomach churns lipids, turning them into small
globules.
• Chyme – thick semi-liquid material made up of small
triacylglycerol globules, other partially digested food,
and gastric secretions.
• Gastric lipase hydrolyzes 10% of TAGs to
monoacylglycerols.
Small Intestine
• Chyme in small intestine triggers hormone
cholecystokinin.
• Cholecystokinin stimulates release of bile in
gallbladder.
• Bile emulsifies lipids.
• Pancreatic lipases hydrolyze ester linkages
between glycerol and fatty acid units.

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 Lymphatic System TRIACYLGLYCEROL STORAGE AND
• Lacteals absorb chylomicrons. MOBILIZATION
➔ Lacteals are lymphatic vessels lining the small Triacylglycerol Storage
intestine. • Adipocyte – triacylglycerol-storing cell
• Chylomicrons mix with lymph, forming chyle. ➔ Largest cells in the body
• Lymphatic vessels carry chylomicrons to the thoracic • Adipose tissue – tissue containing large numbers of
duct. adipocytes.
• Thoracic duct empties into a vein.

• Adipose tissue is located primarily directly beneath

Bloodstream the skin.
➔ Serves as insulator against excessive heat loss
• Lipoprotein lipases hydrolyze TAGs into glycerol and
Provides organs with protection against physical
free fatty acids again.
shock
• These enzymes are found in muscles and other
tissues. Triacylglycerol Mobilization
• Hormones trigger use of TAGs in adipose tissue for
energy production.
• Hormones stimulate production of cAMP inside
adipocyte.
• cAMP activates hormone-sensitive lipase (HSL).
• HSL hydrolyzes TAGs.
• Triacylglycerol mobilization is the hydrolysis of
TAGs store in adipose tissue, followed by release

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 into the bloodstream of the fatty acids and glycerol
so produced.

GLYCEROL METABOLISM ẞ-Oxidation Pathway

• Glycerol travels to liver or kidneys • The ẞ-oxidation pathway is a repetitive series of
• Step 1: Glycerol is phosphorylated by glycerol four biochemical reactions that degrade acyl CoA to
kinase into glycerol 3-phosphate. acetyl CoA by removing two carbon atoms at a time,
• Step 2: Glycerol 3-phosphate is oxidized by glycerol with FADH2 and NADH also being produced.
3- phosphate dehydrogenase into dihydroxyacetone
phosphate.

OXIDATION OF FATTY ACIDS

❑ Three parts
o Activation by bonding to CoA
o Transportation into the mitochondrial matrix by
a shuttle mechanism
o Repeated oxidation, cycling through a series of
four reactions, to produce acetyl CoA, FADH2,
and NADH
Fatty Acid Activation
• Takes place in outer mitochondrial membrane
• FA reacts with coenzyme A in the presence of ATP
to produce high-energy acyl CoA
• ATP is converted to AMP

Fatty Acid Transport

• Fatty acid oxidation occurs inside the mitochondrial
matrix.
• Acyl CoA is too large to pass through the inner
mitochondrial membrane.
• Acyl group is transferred to carnitine.
• Acyl carnitine enters the mitochondrial matrix.
• Acyl group is transferred to CoA.
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 OXIDATION OF SATURATED FATTY ACIDS ATP PRODUCTION
Step 1: Dehydrogenation • ATP produced depends on number of carbon atoms.
• Hydrogen atoms are removed from the α and ẞ • E.g. stearic acid (C18) requires 8 repetitions of ẞ-
carbons, creating a double bond between these two oxidation pathway
carbon atoms.
• Enzyme: Acyl CoA dehydrogenase

Step 2: Hydration
• Water is added across the trans double bond,
producing a secondary alcohol at the ẞ-carbon
position • Glucose (C6) produces only 30 ATP
• Enzyme: Enoyl CoA hydratase • 3 glucose molecules (C18) produce only 90 ATP
• Stearic acid (C18) produces 120 ATP
• Thus, lipids are more efficient as storage and source
of energy.
KETOGENESIS
Step 3: Second Dehydrogenation Acetyl CoA
• Removal of two hydrogen atoms converts the ẞ- • Most of acetyl CoA produced from ẞ-oxidation
hydroxy group to a keto group pathway is used in citric acid cycle.
• Enzyme: ẞ-hydroxyacyl CoA dehydrogenase • Oxaloacetate is needed to react with acetyl CoA.
• Oxaloacetate depends on pyruvate produced from
glycolysis.
• Pyruvate can be converted by pyruvate carboxylase
into oxaloacetate.
Step 4: Thiolysis
• Fatty acid carbon chain is broken between the α and
ẞ carbons by reaction with CoA

Oxaloacetate
• Several conditions can decrease oxaloacetate
OXIDATION OF UNSATURATED FATTY ACIDS concentration:
❑ Step 1: Epimerase changes D-fatty acids to L-fatty ○ High-fat, low-carbohydrate diet
acids. ○ Diabetes
○ Prolonged fasting
Ketone Bodies
• When there is too much acetyl CoA for citric acid
cycle, excess is converted to ketone bodies.
❑ Step 2: Cis-trans isomerase changes cis-(3,4) • A ketone body is one of three substances
double bond to trans-(2,3) double bond. (acetoacetate, β- hydroxybutyrate, and acetone)
produced from acetyl CoA when an excess of acetyl
CoA from fatty acid degradation accumulates
because of triacylglycerol–carbohydrate metabolic
imbalances.

❑ Trans fatty acids then enter step 2 of the ẞ-oxidation

pathway.

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 Step 3: Chain Cleavage
• HMG-CoA is cleaved to acetyl CoA and
acetoacetate
• Enzyme: HMG-CoA lyase

KETOGENESIS
• Synthesis of ketone bodies from acetyl CoA
• Primarily occurs in liver mitochondria

Step 4: Hydrogenation
• Acetoacetate is reduced to ẞ-hydroxybutyrate
• Enzyme: ẞ-hydroxybutyrate dehydrogenase

LIPOGENESIS
• Synthesis of fatty acids from acetyl CoA
• Takes place in cell cytosol.
• Enzymes are collected into a complex called fatty
acid synthase.
• Lipogenesis intermediates are bonded to acyl carrier
protein.
• Dependent on reducing agent NADPH
• Acetyl CoA is used to form malonyl ACP, which
Step 1: First Condensation
becomes the carrier of the two carbon units.
• Two acetyl CoA molecules combine to produce
• Primary sites are liver, adipose tissue, mammary
acetoacetyl CoA
glands
• Enzyme: Thiolase

Step 2: Second Condensation

• Acetoacetyl CoA reacts with a third acetyl CoA and
water to produce 3-hydroxy-3-methylglutaryl CoA
(HMG-CoA) and CoA–SH.
• Enzyme: HMG-CoA synthase

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 CITRATE-MALATE SHUTTLE SYSTEM
• Acetyl CoA is the starting material of lipogenesis.
• It is generated in mitochondria.
• It cannot pass through the inner mitochondrial
membrane.
• Mitochondrial acetyl CoA reacts with oxaloacetate to
produce citrate.
• Citrate is transported to the cytosol. CHAIN ELONGATION
• Citrate is converted back to oxaloacetate, producing • Involves four reactions with fatty acid synthase
acetyl CoA and malate. complex.
• Malate enters the mitochondria. • Fourth step repeats, adding two carbons to the
• Malate is converted to oxaloacetate. chain.
• Stops upon formation of C16 acyl group (palmitic
acid).
➔ Different enzymes needed for further elongation.

ACP COMPLEX FORMATION

• All intermediates in fatty acid synthesis are linked to
carrier proteins (ACP-SH)
• ACP-SH can be regarded as a “giant CoA-SH
molecule”
• Acetyl CoA is converted to either acetyl ACP or
malonyl ACP.
Acetyl ACP Formation
• CP group is transferred to acetyl CoA to form acetyl
ACP.

Malonyl ACP Formation

• Acetyl CoA is carboxylated with ATP to form malonyl
CoA.

• ACP group is transferred to malonyl CoA to form

malonyl ACP.

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 Step 1: Condensation • Precursor for bile salts, sex hormones and
• Acetyl ACP and malonyl ACP condense together to adrenal hormones
form acetoacetyl ACP. • Liver synthesizes 1.5-2.0 g of cholesterol every
day from acetyl CoA
• Synthesis (C27) requires at least 15 acetyl CoA
and involves ~27 separate enzymatic steps.

Step 2: First Hydrogenation

• The keto group of the acetoacetyl complex, which
involves the ẞ-carbon atom, is reduced to the
corresponding alcohol by NADPH.
FATE OF ACETYL CoA
• Processing through citric acid cycle, electron
transport chain, oxidative phosphorylation
• Conversion to ketone bodies
Step 3: Dehydration • Stored in the form of TAGs
• The alcohol produced in Step 2 is dehydrated to • Serve as starting material for production of other
introduce a double bond into the molecule. lipids.

Step 4: Second Hydrogenation

• The double bond introduced in Step 3 is converted
to a single bond through hydrogenation.

UNSATURATED FATTY ACID BIOSYNTHESIS

• Synthesis of fatty acids from acetyl CoA
• Hydrogen is removed to form double bonds.
• Requires oxygen, creates water

• In humans and animals, enzymes can introduce

double bonds only between C4 and C5 and between
C9 and C10.
• Thus, the essential unsaturated fatty acids linoleic
acid (18:2 Δ9,12) and linolenic acid (18:3 Δ9,12,15)
cannot be biosynthesize
➔ They must be obtained from the diet.
BIOSYNTHESIS OF CHOLESTEROL
❑ Cholesterol
• Secondary component of cell membrane

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Interrelationships Among Carbohydrate, Lipid, and
Protein Metabolism

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