BIOCHEMISTRY
CHAPTER 8: LIPID METABOLISM resulting glycerol 3-phosphate is
DIGESTION AND ABSORPTION OF LIPIDS
Lipids are large molecules and generally are not
water-soluble. Like carbohydrates and protein, lipids are
broken into small components for absorption.
• CHYME – is a thick semi-liquid material made up of small
TAG globules, other partially digested food, and gastric
secretions
• FATTY ACID MICELLE – is a micelle in which fatty acids
and/or monoacylglycerols and some bile are present
• CHYLOMICRON – is a lipoprotein that transports TAGs
from intestinal cells via the lymphatic system to the
bloodstream
TAG STORAGE AND MOBILIZATION
ADIPOCYTE – is a triacylglycerol-storing cell
ADIPOSE TISSUE
• a tissue that contains large numbers of adipocyte cells
• located directly beneath the skin (abdominal region) and
in areas around vital organs
• insulator against excessive heat loss to the environment
• provide organs with protection against physical shock
ADIPOSE CELLS – largest cells in the body. They differ
from other cells in that most of the cytoplasm has been
replaced with a large TAG droplet
TRIACYLGLYCEROL MOBILIZATION – is the hydrolysis of
TAGs stored in adipose tissue, followed by release into the
bloodstream of the fatty acids and glycerol so produced.
The TAG energy reserves (fat reserves) are the
human body’s major source of stored energy.
GLYCEROL METABOLISM
The glycerol also enters the bloodstream and is
absorbed by the liver or kidney where it is converted to
glycerol 3-phosphate by the enzyme glycerol kinase, and the
oxidized to
dihydroxyacetone phosphate by the enzyme glycerol-
3phosphate dehydrogenase
OXIDATION OF FATTY ACIDS
THREE PARTS TO THE PROCESS BY WHICH FATTY
ACIDS ARE BROKEN DOWN TO OBTAIN ENERGY
1. the fatty acid must be activated by bonding to coenzyme
A.
2. the fatty acid must be transported into the mitochondrial
matrix by a shuttle mechanism
3. the fatty acid must be repeatedly oxidized, cycling
through a series of 4 reactions to produce acetyl CoA,
FADH2, and NADH
FATTY ACID ACTIVATION
• the outer mitochondrial membrane is the site of fatty acid
activation, the first stage of fatty acid oxidation
• here, the fatty acid is converted to a high-energy
derivative of coenzyme A. Reactants are the fatty acid,
coenzyme A, and a molecule of ATP
FATTY ACID TRANSPORT
• fatty acids are transported across the inner
mitochondrial membrane in the form of acylcarnitine.
ATP PRODUCTION FROM FATTY ACID OXIDATION
The amount of ATP obtained from fatty acid
oxidation depends on the size of the fatty acid is oxidized.
For our purposes here. we’ll study palmitic acid, a saturated
fatty acid with 16 carbon atoms, as a typical fatty acid in the
human diet. Calculating its energy yield provides a model for
determining the ATP yield of all other fatty acids. The
breakdown by an organism of 1 mol of palmitic acid requires
1 mol of ATP (for activation) and forms 8 mol of acetyl-CoA.
Recall from the metabolism of carbohydrates that each mole
of acetyl-CoA metabolized by the citric acid cycle yields 12
mol of ATP. The complete degradation of 1 mol of palmitic
acid requires the β-oxidation reactions to be repeated seven
times. Thus, 7 mol of NADH and 7 mol of FADH2 are
produced. Reoxidation of these compounds through
respiration yields 3 and 2 mol of ATP, respectively.
KETONE BODIES AND KETOGENESIS
KETONE BODY – one of the three substances
(acetoacetate, B-hydroxybutyrate, and acetone) produced
from acetyl CoA when an excess of acetyl CoA from fatty acid
degradation accumulates because of TAGcarbohydrate
metabolic imbalances.
KETOGENESIS – is the metabolic pathway by which ketone
bodies are synthesized from acetyl CoA.
• The primary site for the process is liver mitochondria
• The first ketone body to be produced in ketogenesis is
acetoacetate
• Some of the acetoacetate produced is next converted
to b-hydroxybutyrate, the second ketone body
• The acetoacetate and ß-hydroxybutyrate synthesized
by ketogenesis in the liver are released to the
 bloodstream where acetone, the third ketone body, is
produced.
• Acetoacetate is somewhat unstable and can
spontaneously or enzymatically lose its carboxy1 group
to form acetone. Thus, the ketone body acetone is not
actually a product of the metabolic pathway of
ketogenesis.
• The ketone body acetone present in the bloodstream is
a volatile substance that is mainly excreted by
exhalation. Its sweet odor is detectable in the breath of
a diabetic.
• The amount of acetone present is usually small
compared to the concentrations of the other two ketone
bodies.
FOUR STEPS IN THE PROCESS OF KETOGENESIS
1. First condensation
2. Second condensation
3. Chain cleavage
4. Hydrogenation
KETOSIS – is the body condition in which high levels of
ketone bodies are present in both the blood and urine.
Both ketonemia and ketonuria are contributors to the
condition called ketosis. Ketosis is often detectable by the
smell of acetone on a person’s breath; acetone is very volatile
and is excreted through the lungs.
BIOSYNTHESIS OF FATTY ACIDS: LIPOGENESIS
Lipogenesis is the metabolic pathway by which fatty
acids are synthesized from acetyl CoA. Fatty acid
biosynthesis (lipogenesis) occurs anytime dietary intake
provides more nutrients that are needed for energy
requirements. The primary lipogenesis sites are the liver,
adipose tissue, and mammary glands. The mammary glands
show increased synthetic activity during periods of lactation.
• Lipogenesis occurs in the cell cytosol, whereas
degradation of fatty acids occurs in the mitochondrial
matrix. Because they have different reaction sites, these
two opposing processes can occur at the same time
when necessary.
• Different enzymes are involved in the two processes,
Lipogenesis enzymes are collected into a multienzyme
complex called fatty acid synthase. This enzyme
complex ties the reaction steps of lipogenesis closely
together. The enzymes, involved in fatty acid
degradation are not physically associated, so the
reaction steps are independent.
• Intermediates of the two processes are covalently
bonded to different carriers. The carrier for fatty acid
degradation intermediates is CoA. Lipogenesis
intermediates are bonded to ACP (acyl carrier protein).
• Fatty acid synthesis is dependent on the reducing agent
NADPH. Fatty acid degradation is dependent on the
oxidizing agents’ FAD and NAD+
• Fatty acids are built up two carbons at a time during
synthesis and are broken down two carbons at a time
during degradation. The source of the two carbon units
differs between the two processes. In lipogenesis, acetyl
CoA is used to form malony1 ACP, which becomes the
carrier of the two carbon units. CoA derivatives are
involved in all steps of fatty acid degradation.
4 STEPS FOR THE CHAIN ELONGATION PROCESS
• condensation – Acetyl ACP and malonyl ACP
condense together to form acetoacetyl ACP.
• first hydrogenation – the keto group of the
acetoacetyl complex, which involves the B-carbon
atom, is reduced to the corresponding alcohol by
NADPH.
• dehydration – the alcohol produced in step 2 is
dehydrated to introduce a double bond into the
molecule (between the a & B carbons)
• second hydrogenation – the double bond
introduced in step 3 is converted to a single bond
through hydrogenation.
UNSATURATED FATTY ACID BIOSYNTHESIS
Production of unsaturated fatty acids (insertion of
double bonds) requires molecular oxygen (O 2). In an
oxidation step, hydrogen is removed and combined with the
O2 to form water.
In humans and animals, enzymes can introduce double bonds
only between CA
and C5 and between C9 and C10. Thus, the important
unsaturated fatty acids linoleic (C18 with C9 and C12 double
bonds) and linolenic (C18 with C9, C12, and C15 double
bonds) cannot be biosynthesized. They must be obtained
from the diet. (Plants have the enzymes necessary to
synthesize these acids.) Acids such as linoleic and linolenic,
which cannot be synthesized by the body but are necessary
for its proper functioning, are called essential fatty acids.
Lipogenesis can be used to convert glucose to fatty
acids via acetyl COA. The reverse process, conversion of
fatty acids to glucose, is not possible within the human body.
Fatty acids can be broken down to acetyl CoA, but there is
no enzyme present for the conversion of acetyl CoA to
pyruvate or oxaloacetate, starting materials for
gluconeogenesis (Section 7-6). Plants and some bacteria do
possess the needed enzymes and thus can convert fatty
acids to carbohydrates.
RELATIONSHIPS BETWEEN LIPOGENESIS AND
CITRIC ACID CYCLE INTERMEDIATES
The intermediates in the last four steps of the citric
acid cycle are all C4 molecules. In the first cycle of the four
repetitive reactions in lipogenesis, all of the carbon chains
attached to ACP are C4 chains. A lot of relationships exist
between the two sets of C4 entities. The last four
intermediates of the citric acid cycle bear the ff. 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 ff. relationship to each
other: keto C4 monoacid – hydroxy C4 monoacid –
unsaturated C4 monoacid – saturated C4 monoacid.
FATE OF FATTY ACID GENERATED ACETYL COA
• The acetyl CoA can be further processed through
the common metabolic pathway (CAC, ETC, and
oxidative phosphorylation) to obtain ATP.
• The acetyl CoA can undergo conversion to ketone
bodies. Such ketone bodies can be reconverted.
when needed, back to acetyl CoA, which can then
be processed for ATP production.
• The acetyl CoA can be stored in the body in the
form of TAGs by reconverting via lipogenesis the
 acetyl CoA to fatty acids that are then converted
to TAGs. (Fatty acids, once synthesized do not
react directly with glycerol to form TAG
molecules. Glycerol must first be
activated. The energy for this activation is supplied by
an ATP molecule and glycerol 1-phosphate is the
activation product)
• The acetyl COA can be used as the starting
material for the production of lipids other than fatty
acids that the body needs. A specific example of
such “other lipid" production is the biosynthesis of
cholesterol. Cholesterol is a necessary
component of cell membranes. It is also the
precursor for bile salts, sex hormones, and
adrenal hormones.
• It is also important to note what cannot happen to
the acetyl CoA obtained from fatty acid oxidation.
In humans and animals, it cannot be used for the
net synthesis of glucose. Pyruvate or oxaloacetate
is the needed starting material for glucose
production via
gluconeogenesis. Humans and animals do not
possess the enzymes needed to convert acetyl
CoA to pyruvate. (By contrast, plants do contain
the two additional enzymes needed.) Pyruvate
can be
converted to acetyl CA in a reaction sequence that
is irreversible. Acetyl COA cannot be converted to
pyruvate.
RELATIONSHIPS BETWEEN LIPID AND
CARBOHYDRATE METABOLISM
Acetyl CoA is the primary link between lipid and
carbohydrate metabolism. In interrelationships between
Carbohydrate and Lipid metabolism, acetyl CoA is the
degradation product for glucose, glycerol, and fatty
acids,
and it is also the starting material for the biosynthesis of fatty
acids, cholesterol, and ketone bodies.
Some of the reactions associated with carbohydrate and lipid
metabolism occur within the mitochondrion and
others occur within the cytosol
B VITAMINS AND LIPID METABOLISM
For the processes of B-oxidation, ketogenesis,
and lipogenesis, 4 of the 8 B vitamins are needed.
These are niacin, riboflavin (FAD), pantothenic acid
(CoA, acetyl CoA, and ACP) and biotin.
PROTEIN DIGESTION AND ABSORPTION
Digestion of proteins involves the hydrolysis of the peptide
bonds that link amino acids to each other. This process
begins in the stomach and is completed in the small
intestine. The amino acids released by digestion are
absorbed through
the intestinal wall into the bloodstream
AMINO ACID UTILIZATION
• AMINO ACID POOL - the total supply of free amino acids
available for use in the human body
• PROTEIN TURNOVER - the repetitive process in which
proteins are degraded and resynthesized within the
human body
• NITROGEN BALANCE - is the state that results when the
amount of nitrogen taken into the human body as protein
equals the amount of nitrogen excreted from the body in
waste materials
3 SOURCES THAT CONTRIBUTE AMINO ACID TO THE
AMINO ACID POOL
o Dietary Protein
o Protein Turnover
o Biosynthesis
TWO TYPES OF NITROGEN IMBALANCE
• NEGATIVE NITROGEN BALANCE
• POSITIVE NITROGEN BALANCE
TRANSAMINATION AND OXIDATIVE DEAMINATION
THE UREA CYCLE
AMINO ACID CARBON SKELETONS
• Difference between glucogenic amino acid and
ketogenic amino acid:
o GLUCOGENIC – has a carbon-containing
degradation product that can be used to produce
glucose via gluconeogenesis
o KETOGENIC – has a carbon-containing
degradation product that can be used to produce
ketone bodies