BIOCHEMISTRY FOR MEDICAL LABORATORY SCIENCE
SAMANTHA GRICEL L. MENDOZA | BSMLS 2-Y1-2
TOPIC: LIPID METABOLISM
DIGESTION AND ABSORPTION OF LIPIDS
Dietary Lipids: 98% triacylglycerols (TAGs):
● Fats and oils
- Salivary enzymes (water soluble) in the mouth have
no effect on lipids (TAGs) which are water insoluble
- In Stomach: Most, not all, of TAGs change physically
to small globules or droplets -- called chyme which
floats above other material:
- It is a physical not chemical process --
enters into small intestine
Lipid digestion starts in the stomach:
- Gastric lipase hydrolyzes ester bonds -- 2 fatty
acids and one monoacylglycerol --About 10% of
TAGS are hydrolyzed
● High fat foods stay in stomach for longer
time -- high fat meal gives you a feeling of
being full for longer time
- Chyme enters into small intestine and is emulsified
(stabilization of colloidal suspension) with bile salts
- Pancreatic lipase hydrolyzes ester bonds of fatty
acids and glycerol
- Normally 2 out of 3 fatty acids are
hydrolyzed
- Fatty acids, monoacyglycerols and bile salts make
small droplets: called micelles -- hydrophobic chain
in the interior
- Micelles consist of monoacyglycerols and free fatty
acids:
- Small enough to absorb through intestinal
cells
- In the intestinal cells monoacylglycerols and free
fatty acids are repackaged to from TAGs
- These new TAGs combine with membrane lipids
(phospholipids and cholesterol) and lipoproteins to
form chylomicron
- Chylomicrons transport TAGs from intestinal cells
to the bloodstream
- This is accomplished though the lymphatic
system
- In the bloodstream TAGs are completely hydrolyzed
by lipase enzymes
FINALS | LECTURE
- Fatty acids and glycerol are absorbed by the cell
and are either broken down to the acetyl Co-A for
energy or repacked to store as lipids
TRIACYLGLYCEROL STORAGE AND MOBILIZATION
- Most cells have limited capability of TAGs storage
- TAGs stored in specialized cells called adipocytes
found in adipose tissue:
● Largest cells in the body -- cytoplasm
converted to TAG’s droplet
● Located primarily beneath the skin
especially in abdominal region and vital
organs
● Adipose tissue also serve as a protection
against the heat loss and mechanical
shock
- Several hormones trigger the hydrolysis of TAGs via
activation of cAMP (activate hormone sensitive
lipase; HSL) and release of glycerol and fatty acids
into the bloodstream -- called triacylglycerol
mobilization
- ~10% of TAGs replaced everyday
- Triacylglycerol energy reserves (fat reserves) are
the human body’s major source of stored energy:
● Energy reserves associated with protein,
glycogen, and glucose are small to very
small when compared to fat reserves
GLYCEROL METABOLISM
- Taken to liver or kidney by blood -- converted to
dihydroxyacetone phosphate in two steps:
● Phosphorylation of primary hydroxyl
group of the glycerol
● Secondary alcohol group of glycerol is
oxidized to ketone
BIOCHEMISTRY FOR MEDICAL LABORATORY SCIENCE
SAMANTHA GRICEL L. MENDOZA | BSMLS 2-Y1-2
OXIDATION OF FATTY ACIDS
- There are three parts to the process by which fatty
acids are broken down to obtain energy
- Activated by binding to Coenzyme-A - product
called acyl Co-A.
- Transported to mitochondrial matrix
- Repeatedly (fatty acid spiral) oxidized to produce
acetyl Coa, FADH2 and NADH
● note acyl has longer R group but acetyl
has CH3 attached to C=O
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
- A shuttle mechanism is involved in the transport of
acyl CoA from mitochondrial membrane to
mitochondrial matrix
REACTIONS OF THE BETA-OXIDATION PATHWAY
- Four reactions repeatedly cleaves two-carbon units
from the carboxyl end of saturated fatty acids
● Also called b-oxidation spiral because the
second or beta carbon from carboxyl end
of the chain oxidized
- This process removes two carbon units and
converts to acetyl CoA with FADH2 and NADH being
produced
FINALS | LECTURE
4 STEPS OF THE BETA-OXIDATION PATHWAY
STEP 1: OXIDATION (DEHYDROGENATION)
- Hydrogen atoms are removed from the a and b
carbons, creating a double bond between these two
carbon atoms.
- FAD is the oxidizing agent, and a FADH2 molecule is
a product.
STEP 2: HYDRATION
- A molecule of water is added across the trans
double bond, producing a secondary alcohol at the
b-carbon position
STEP 3: OXIDATION (DEHYDROGENATION)
- The β-hydroxy group is oxidized to a ketone
functional group with NAD+ serving as the oxidizing
agent.
STEP 4: CHAIN CLEAVAGE
- The fatty acid chain is broken between the α and β
carbons by reaction with a coenzyme A molecule.
- The result is an acetyl CoA molecule and a new acyl
CoA molecule that is shorter by two carbon atoms
than its predecessor.
UNSATURATED FATTY ACID
- Oxidation of unsaturated FAs require two additional
steps compared to saturated FAs
Epimerase: changes D-configuration to an L configuration
Cis-trans isomerase: trans-(2,3) double bond is formed from
cis-(3,4) double bond
ATP PRODUCTION FROM FATTY ACID OXIDATION
FATTY ACID VS. GLUCOSE OXIDATION: A COMPARISON
- Spiral fatty acid oxidation (previous slide) produce
net 120 ATP molecules by oxidation of 18 carbon
atom fatty acid (stearic acid)
- Note that 2 ATP molecules are needed for
activation of fatty acids so net ATP production is
120 molecules
- 1 Glucose molecule (6 carbon atoms) produces 30
ATP molecules
- Three molecules of glucose (18 Carbon atoms)
produce 90 ATP
- 1 Stearic acid molecule (18 carbon atoms) produces
122 molecules of ATP
BIOCHEMISTRY FOR MEDICAL LABORATORY SCIENCE
SAMANTHA GRICEL L. MENDOZA | BSMLS 2-Y1-2 FINALS | LECTURE

STOICHIOMETRIC COMPARISON BIOSYNTHESIS OF FATTY ACIDS: LIPOGENESIS

- 1.00 g Stearic acid produces = 0.423 mole ATP Lipogenesis Degradation of fatty acids
- 1.00 g glucose produces 0.167 mole ATP
- Stearic acid produces 2.5 time more
Takes place in cell cytosol Takes place in mitochondrial
energy than glucose
matrix

KETONE BODIES
A multi-enzyme complex Enzymes are not complexed
- Acetyl CoA formed from fatty acid spiral further called fatty acid synthase and the steps are
processed by Citric Acid Cycle (Krebs Cycle) – catalyzes reactions independent
Therefore an adequate balance in carbohydrate and
lipid metabolism required
Intermediates bonded to The carrier for fatty acid
Lipid-Carbohydrate Metabolism disturbed by: acyl carrier protein (ACP) spiral is CoA
● Dietary intakes high in fat and low in
carbohydrates
● Diabetic conditions -- glucose not used Depends upon reducing Dependent upon FAD and
properly agent NADPH NAD+
● Prolonged fasting conditions
THE CITRATE-MALATE SHUTTLE SYSTEM
- Under low supply of oxaloacetate the acetyl CoA
will be in excess (increased concentration) - Acetyl CoA is the starting material for lipogenesis.
- As a consequence the excess acetyl CoA is - Acetyl CoA needed for lipogenesis is generated in
converted to ketone bodies mitochondria therefore it must first be transported
to the cytosol.
KETOGENESIS - Citrate-malate transport system helps transport
acetyl CoA to cytosol indirectly.
- Ketogenesis involves the production of ketone
bodies from acetyl CoA ACP COMPLEX FORMATION
- Synthesis of ketone bodies from acetyl CoA
primarily in liver mitochondria -- diffused into - All intermediates in fatty acid synthesis are linked
blood stream and transported to peripheral tissues to carrier proteins (ACP-SH)
- ACP-SH can be regarded as a “giant CoA-SH
Step 1: First Condensation molecule”
- Of two acetyl CoA molecules to produce
acetoacetyl CoA, a reversal of the last step of the CHAIN ELONGATION
Beta-oxidation pathway
Four reactions constitute the first step of the chain
Step 2: Second Condensation elongation process
- Acetoacetyl CoA then reacts with a third acetyl CoA
and water to produce 3-hydroxy-3-methylglutaryl Condensation:
CoA (HMG-CoA) and CoA-SH. - Acetyl-ACP and malonyl-ACP condense together to
form acetoacetyl-ACP
Step 3: Chain cleavage
- HMG-CoA is cleaved to acetyl CoA and Hydrogenation:
acetoacetate. - The keto group of the acetoacetyl complex is
reduced to alcohol by NADPH
Step 4: Reduction
- Acetoacetate is reduced to Beta- hydroxybutyrate. Dehydration:
SUMMARY OF KETOGENESIS - Water is removed from alcohol to form an alkene

Hydrogenation:
- Hydrogen is added to alkene 3 to form saturated
butyryl ACP from NADPH
BIOCHEMISTRY FOR MEDICAL LABORATORY SCIENCE
SAMANTHA GRICEL L. MENDOZA | BSMLS 2-Y1-2 FINALS | LECTURE

UNSATURATED FATTY ACID BIOSYNTHESIS BIOSYNTHETIC RELATIONSHIPS AMONG STEROID

- To produce a double bond oxygen is needed and
water is removed
- In humans and animals, enzymes can only
introduce double bond between C-4 and C-5 and
between C-9 and C-10
HORMONES
- Once cholesterol is synthesized, it is converted to
five major classes of steroid hormones: progestins,
androgens, estrogens and vitamin D

Consequence: Important essential unsaturated fatty acids

linoleic (18 carbons with C-9 and C-12 double bond and
linolenic acid (18 carbon with C-9, C-12 and C-15 double
bonds can’t be synthesized - should come from diet - plants
have enzymes to synthesize them

RELATIONSHIPS BETWEEN LIPOGENESIS AND CITRIC RELATIONSHIPS BETWEEN LIPID AND CARBOHYDRATE
ACID CYCLE INTERMEDIATE METABOLISM

- The last four intermediates of the citric acid cycle
bear the following relationship to each other.
- Saturated C4 diacid -> Unsaturated C4 diacid ->
hydroxy C4 diacid -> keto C4 diacid.
- The intermediate C4 carbon chains of lipogenesis
bear the following relationship to each other.
- Keto C4 monoacid -> hydroxy C4 monoacid ->
unsaturated C4 monoacid -> saturated C4 monoacid.
CONTRASTS BETWEEN CITRIC ACID CYCLE AND
LIPOGENESIS INTERMEDIATES
- The citric acid intermediates involve C4 diacids and
the lipogenesis intermediates involve C4 monoacids
- The order in which the various acid derivative types
are encountered in lipogenesis is the reverse of the
order in which they are encountered in the citric
acid cycle.
BIOSYNTHESIS OF CHOLESTEROL
CHOLESTEROL
- Acetyl Co-A is the primary link between these two
metabolic pathways
● Acetyl Co-A is the starting material for the
biosynthesis of fatty acids, cholesterol and
ketone bodies
● Acetyl CoA is the product for glucose,
glycerol and fatty acids
FOUR POSSIBLE FATES OF ACETYL COA
- Oxidation in the citric acid cycle: both lipids and
carbohydrates supply acetyl CoA
- Ketone body formation: Very important when
imbalance between carbohydrate and lipid
metabolism
- Fatty acid biosynthesis: the buildup of excess acetyl
CoA when dietary intake exceeds energy needs
energy needs leads to accelerated fatty acid
biosynthesis
- Cholesterol biosynthesis: It occurs when the body is
in an acetyl CoA- rich state

- Secondary component of cell membrane

- Precursor for bile salts, sex hormones and adrenal
hormone
- Body synthesizes 1.5 - 2.0 g of cholesterol everyday
from acetyl CoA units
● Average daily dietary intake is ~ 0.3
- Synthesis of cholesterol occur in liver
- Synthesis requires at least 15 acetyl CoAs and
involves
● 27 separate enzymetic steps
OVERVIEW OF BIOSYNTHETIC PATHWAY FOR
CHOLESTEROL SYNTHESIS