LIPID METABOLISM NRG 104 -

Davao Doctor’s College – Nursing Program

Ma’am Joyce, M. (Instructor) || BSN BIOCHEMISTRY
BATCH 2025
Transcribe by: Galaura, Stanley A.

o Fatty acid micelles are very small compared to

Digestion and Absorption of Lipids the original triacyclglycerols globules, which
contain thousands of triacylglycerol molecules
• Dietary Lipids: 98% triacylglycerols, TAGS: Fats and
o Micelles, containing free fatty acid and
oils
monoglycerol components are small enough to
• Salivary Enzymes (water soluble) in the mouth have
be readily absorbed through the membranes
no effect on lipids (TAGS) which are water insoluble
of intestinal cells
o Major change that TAGS undergo in the stomach
o Within the intestinal cells, a repackaging
is physical rather than chemical
occurs in which the free fatty acids and
o The churning action of the stomach breaks up
monoacylglycerols are reassembled into
triacylglycerol materials into small globules, or
triacylglycerols.
droplets, which float as a layer above the other
o The newly formed triacylglycerols are then
components of swallowed food.
combined with membrane lipids
o In Stomach: Most, not all of TAGS change
(phospholipids and cholesterol) and water-
physically to small globules or droplets
soluble proteins to produce a type of
• Chyme – floats above other material
lipoprotein called a chylomicron.
→ Thick semi-liquid material made up
o Chylomicron – a lipoprotein that transports
of small triacylglycerols globules,
triacylglycerols from intestinal cells, via the
other partially food, and gastric
lymphatic system to the blood stream
secretions (hydrochloric acid and
o Triacylglycerols constitute 95% of the
several enzymes) core lipids present in a chylomicron
• High fat foods remain in the stomach longer than low- o Chylomicrons are too large to pass
fat foods. The conversion of high-fat materials into through capillary walls directly into the
chyme takes longer than the breakup of low-fat bloodstream
materials. o Consequently, delivery of the
o This is why a high-fat meal causes a person to feel chylomicrons to the blood stream is
full for a longer periods of time accomplished through the body’s
• Lipid digestions begins in the stomach lymphatic system.
o Under the action of gastric lipase enzymes, o Chylomicrons enter the lymphatic
hydrolysis of TAGS occurs system through tiny lymphatic vessels
o About 10% of TAGS undergo hydrolysis in the in the intestinal lining
stomach, but regular consumption of a high-fat o They enter the blood stream through
diet can induce the production of higher levels of the thoracic duct (large lymphatic
gastric lipases.
vessel just below the collarbone),
o The arrival of chyme from the stomach triggers in where the fluid of the lymphatic
the small intestine, through the action of the system flows into a vein joining the
hormone cholecystokinin – the release of bile bloodstream
stored in the gall bladder
o One the chylomicrons reach the blood
o The bile, which contains no enzymes, act as an
stream, the TAGs they carry are again
emulsifier
hydrolyzed to produce glycerol and
o Colloid particle formation through bile
free fatty acids
emulsification “solubilizes” the triacylglycerol
▪ TAG release from
globules, and digestion of the TAGs resumes.
chylomicrons and their
• The major enzymes involved at this point are the
ensuing hydrolysis are
pancreatic lipases, which hydrolyze ester linkages
mediated by lipoprotein
between the glycerol and fatty acid units of the TAGS
lipases.
o Complete hydrolysis does not usually occur, only
• These enzymes are
2 of the 3 fatty acid units are liberated, producing
a monoglycerol and 2 free fatty acids located on the lining
o Occasionally, enzymes remove all 3 fatty acid of blood vessels in the
units, leaving a free glycerol molecule muscle and other
o With the help of bile, the free fatty acids and tissue that use fatty
monoglycerols produced from hydrolysis are acids for fuel and fat
combined into tiny spherical droplets called synthesis.
micelles. • The fatty acid and glycerol hydrolysis products from
• Fatty Acid micelle – is a micelle in which fatty acids TAG hydrolysis are absorbed by the cells of the body
and monoacylglycerols and some bile are present and are either broken down to acetyl CoA for energy

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[BIOCHEMISTRY] LIPID METABOLISM – Ma’am Joyce
Ann Muico
or stored as lipids (they are again repackaged as • Triacylglycerol reserves would enable the
TAGs) average person to survive starvations for
o Soon after a meal heavily laden with TAGS is about 30 days, given sufficient water
ingested, the chylomicron content of both o Glycogen reserves (stored glucose) would
blood and lymph increases dramatically. be depleted within 1 day
o Chylomicron concentrations usually being to o Dietary TAGs deposited in adipose tissue
rise within 2 hours after a meal, reach a peak have undergone hydrolysis 2 times (to
in 4-6 hrs., and then drop rather rapidly to a form free fatty acids and/or
normal level as chylomicrons move into monoacylglycerols) and are repackaged
adipose cells or into the liver. twice (to re-form TAGs) in reaching that
state
Triacylglycerol Storage and Mobilization o They undergo hydrolysis for a 3rd time
when triacylglycerol mobilization occurs.
• Most cells in the body have limited capability for
storage of TAGS
• However, this activity is the major function of
specialized cells called adipocytes, found in
adipose tissue
• Adipocyte – a triacylglycerol storing cell
• Adipose Tissue – contain large numbers of
adipocyte cells
o Located primarily directed beneath the skin
(subcutaneous), particularly in the abdominal
region, and in areas around vital organs
o Besides its function as a storage location for the
chemical energy inherent in TAGs, subcutaneous
tissue serves as an insulator against excessive
heat loss to the environment and provides organs Digestion and Absorption of Lipids
with protection against physical shock • Lipid digestion starts in the stomach
o Adipose cells are among the largest cells in the o Gastric lipase hydrolyzes ester bonds – 2 fatty
body acids and 1 monoacylglycerol – about 10% of
o They differ from other cells, in that most of the TAGS are hydrolyzed.
cytoplasm has been replaced with a large o High fat foods stay in stomach for longer time
triacylglycerol droplet – high fat meal gives you a feeling of full.
o This droplet accounts for nearly the entire volume o Chyme enters into small intestine and is
of the cell emulsified with bile salts
• Use of the TAGs stored in adipose tissue for energy o Pancreatic lipase hydrolyzes ester bonds to
production is triggered by hormones – epinephrine form fatty acids and glycerol
ang glucagon. o Normally 2 out of 3 fatty acids are
o Hormonal interaction with adipose cell membrane hydrolyzed
receptors stimulates production of cAMP from ATP o Fatty acids, monoacylglycerols and bile salts
inside the adipose cell make small droplets – called micelles –
o In a series of enzymatic reactions, the cAMP hydrophobic chain in the interior.
activates hormone-sensitive ligase (HSL) through o Micelles consist of monoacylglycerol and free
phosphorylation fatty acids that are small enough to absorb
o HSL is the lipase needed for triacylglycerol through the intestinal cells.
hydrolysis, a prerequisite for fatty acids to enter
the bloodstream from an adipose cell. Glycerol Metabolism
• Triacylglycerol mobilization – is the hydrolysis of • During triacylglycerol mobilization, 1 molecule of
triacylglycerol stored in adipose tissue, followed by glycerol is produced for each triacylglycerol molecule
release into the bloodstream of the fatty acids and completely hydrolyzed
glycerol so produced. o After entering the bloodstream, the glycerol
• Triacylglycerol mobilization is an ongoing process travels to the liver or kidneys, where the 1st stage
• About 10% of the TAGs in adipose tissue are of glycerol metabolism occurs
replaced daily by new triacylglycerol molecules. o At this location it is converted to dihydroxyacetone
• Triacylglycerol energy reserves (fat reserves) are phosphate, a glycolysis/gluconeogenesis
the human body’s major source of stored energy. intermediate
o The dihydroxyacetone phosphate can be
• Energy reserves associated with protein, glycogen, converted to pyruvate, then acetyl CoA, and finally
and glucose are small to very small when compared carbon dioxide, or it can be used to form glucose.
to fat reserves • Dihydroxyacetone phosphate formation from glycerol
Notes to remember: represents the first of several situations that will be

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[BIOCHEMISTRY] LIPID METABOLISM – Ma’am Joyce
Ann Muico
encountered where lipid and carbohydrate metabolism • A shuttle mechanism involving the molecule carnitine
are connected effects the entry of acyl.
• The conversion of glycerol to dihydroxyacetone is a 2 o CoA into the matrix
type ATP group of the glycerol o The acyl group is transferred to a carnitine
o The 1st step involves phosphorylation of a primary molecule, which carries it through the
hydroxyl group of the glycerol membrane
o In the 2nd step, glycerol’s secondary alcohol group o The acyl group is then transferred from the
(C2) is oxidized to a ketone carnitine back to a CoA molecule.
• The following equation represents the overall
reaction for the metabolism of glycerol
• Glycerol + ATP + NAD → Dihydroxyacetone Reactions of the B-Oxidation Pathway
phosphate + ADP + NADH + H+ • In the mitochondrial matrix, a sequence of 4 reactions
Oxidation of Fatty Acids repeatedly cleaves two carbon units from the carboxyl
• There are 3 parts to the process by which fatty acids end of the acyl CoA molecule.
are broken down to obtain energy. • This repetitive 4 reaction sequence is called the B-
1. The fatty acid must be activated by bonding to oxidation pathway because
coenzyme A. o The 2nd carbon from the carboxyl end of
2. The fatty acid must be transported into the the chain, the beta carbon, is the carbon
mitochondrial matrix by a shuttle mechanism atom that is oxidized
3. The fatty acid must be repeatedly oxidized, cycling o The B-oxidation pathway is a repetitive
through a series of 4 reactions, to produce acetyl series of 4 biochemical reactions that
CoA, FADH2, and NADH degrade acyl CoA to acetyl CoA by
• The B-Oxidation Theory: Involves the oxidation of the removing 2 carbon atoms at a time, with
2nd carbon atom from the acid end of the fatty acid FADH2 and NADH also being produced.
molecule – the B carbon atom. o Each repetition of the 4 reaction sequence
o In this process B oxidation removes 2 carbon generates an acetyl CoA molecule and an
atoms at a time from the fatty acid chain acyl CoA molecule that has 2 fewer carbon
o That is, an 18-carbon fatty acid is oxidized to atoms
a 16-carbon fatty acid, then to a 14-carbon Fatty Acid Transport
fatty acid, and so on, until the oxidation • Acyl CoA is too large to pass through the inner
process is complete. mitochondrial membrane to the mitochondrial matrix,
o The Acetyl CoA thus produced enters the where the enzymes needed for fatty acid oxidation are
Krebs Cycle and the new molecule of active located
fatty acid goes through the same sequence • A shuttle mechanism involving the molecule carnitine
again, each time losing two carbon atoms until effects the entry of acyl
the entire fatty acid molecules has been o CoA into the matrix
oxidized. o The acyl group is transferred to a carnitine
Fatty Acid Activation molecule, which carries it through the
• The outer mitochondrial membrane is the site of fatty membrane
acid activation, the 1st stage of fatty acid oxidation. o The acyl group is then transferred from
• Here the fatty acid is converted to a high-energy the carnitine back to a CoA molecule.
derivative of coenzyme A. Ketone (Acetone) Bodies
o Reactants are the fatty acid, coenzyme A, and a
molecule of ATP. • In a diabetic patient, or in any other situation in which
o This reaction requires the expenditure of two high- carbohydrate metabolism is restricted, the body uses
energy phosphate bonds from a single ATP oxaloacetate to produce glucose for the brain and
molecule;
muscles.
o The ATP is converted to AMP rather than ADP, and • This reduces the amount of oxalate available for the
the resulting pyrophosphate (PPi) is hydrolyzed to
Krebs cycle, and acetyl CoA cannot be properly
2Pi.
metabolized.
o The activated fatty acid-CoA molecule is called
• When this occurs, the acetyl CoA is changed to
Acyl CoA.
acetoacetyl CoA, which is converted into acetoacetic
o The difference between the designations acyl CoA
acid in the liver by the enzyme deacylase.
and acetyl CoA is that acyl refers to a random
• Acetoacetic acid may be changed into acetone and B-
length fatty acid carbon chain that is covalently
hydroxybutyric acid.
bonded to coenzyme A, whereas acetyl refers to a
2-carbon chain covalently bonded to coenzyme A. • For the vast majority of persons following a low-
Fatty Acid Transport carbohydrate diet, the effects of ketosis appear to be
harmless or nearly so.
• Acyl CoA is too large to pass through the inner
o The symptoms of the mild ketosis that occurs
mitochondrial membrane to the mitochondrial matrix,
as the result of such dieting include:
where the enzymes needed for fatty acid oxidation are
headache, dry, mouth, and sometimes
located.
acetone-smelling breath.

STANLEY G. – BACHELOR OF SCIENCE IN NURSING 3

[BIOCHEMISTRY] LIPID METABOLISM – Ma’am Joyce
Ann Muico o Typically, the same is true for fasting - Condensation: Acetyl-ACP and
situations: only mild ketosis effects are malonyl-ACP condense together to
observed. form acetoacetyl-ACP
o A serious to extremely serious ketosis problem - Hydrogenation: the keto group of
called ketoacidosis can develop in persons the acetoacetyl complex is reduced to
with uncontrolled type 1 diabetes alcohol by NADPH
o 2 of the 3 ketone bodies: acetoacetate and B- - Dehydration: water is removed from
hydroxybutyric – acids; a carboxyl group is alcohol to form an alkene
present in their structure - Hydrogenation: hydrogen is added
to alkene 3 to form saturated butyryl
Ketone Bodies ACP from NADPH
• During ketosis acetone may be detected on the • In the first turn of the fatty acid biosynthetic pathway,
patient’s breath because its volatile compound and is acetyl ACP is converted to butyryl ACP in the next
easily excreted through the lungs cycle, the butyryl ACP reacts with another malonyl ACP
• Ketosis may occur with diabetes mellitus, in to produce a 6-carbon acid
starvation, or severe liver damage or on a diet high in • Continued cycles produce acids 8,10,12,14, and
fats and low in carbohydrates 16 carbon atoms
• During diabetes mellitus, the body is unable to oxidize • Elongation of the acyl group chain through this
carbohydrates and instead oxidizes fats leading to an procedure, which is tied to the fatty acid synthase
accumulation of ketone bodies in the blood and the complex, stops upon formation of the C16 acyl group
urine; the ketone bodies are acidic and tend to (palmitic acid).
decrease the pH of the blood leading to acidosis which
may lead to fatal coma.
o During acidosis, an increased amount of water
intake is needed to eliminate the products of
metabolism. Unless the water intake of diabetic is
increased, dehydration will occur.
o Dehydration of diabetics may also be caused by
polyuria due to an increased amount of glucose
in the urine.
• Likewise, during prolonged starvation or on a high-fat,
low-carbohydrate diet, the body tends to burn fat
instead of carbohydrates leading to ketosis and
acidosis.
• In severe liver damage, the liver cannot store
glycogen in the required amounts so that the
carbohydrates are not available for the normal
oxidation of fats, leading to ketosis.

Biosynthesis of Fatty Acids: Lipogenesis

• Acetyl CoA is the starting material of lipogenesis
• Acetyl CoA needed for lipogenesis is generated in
mitochondria, therefore it must first be transported to
the cytosol
• Citrate-malate transport system helps transport acetyl
CoA to cytosol indirectly.
• Cytoplasmic acetyl CoA is converted to malonyl CoA in
a carboxylation reaction that involves CO2 and ATP.
• Reaction occurs only when cellular ATP levels are high
catalyzed by acetyl CoA carboxylase complex, which
requires both Mn2+ and biotin for its activity.
• ACP (Acyl carrier protein) 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.
Chain elongation
• Four reactions constitute the steps of chain elongation
process.

STANLEY G. – BACHELOR OF SCIENCE IN NURSING 4