Spencer L. Seager
Michael R. Slabaugh
www.cengage.com/chemistry/seager
Chapter 24:
Lipid and Amino Acid Metabolism
Jennifer P. Harris
LIPID METABOLISM – BLOOD LIPIDS
• During digestion, lipids are
hydrolyzed to glycerol, fatty
acids, and monoglycerides.
• For transport in the lymph
and blood, the cells of the
small intestines produce
lipoprotein aggregates called
chylomicrons.
LIPID METABOLISM – BLOOD LIPIDS
(continued)
• Behavior of blood lipids parallels that of blood sugar.
• The concentrations of both increase after a meal.
• The concentrations of both return to normal as a result of:
• storage in fat depots.
• oxidation to provide energy.
• Plasma lipids concentrations:
• rise within 2 hours of a meal.
• reach a peak in 4-6 hours.
• drop rapidly to a normal level.
BLOOD LIPID CLASSIFICATION
• Lipids are less dense than proteins.
• The classification of blood lipids is based on density.
• The higher the lipid concentration of a lipoprotein aggregate,
the lower the density.
VLDL = very low density lipoprotein
LDL = low density lipoprotein
HDL = high density lipoprotein
SCHEMATIC MODEL OF LDL
FAT MOBILIZATION (continued)
• Fatty acids stored in triglycerides are called on as energy
sources:
• after a few hours of fasting.
• even when glycogen supplies are adequate by resting
muscle and liver cells, because it:
• conserves the body’s glycogen stores and glucose for
brain cells and red blood cells.
• Brain cells do not obtain nutrients from blood.
• Red blood cells do not have mitochondria;
therefore, red blood cells do not have fatty acid
oxidation.
FAT MOBILIZATION (continued)
• Triglycerides are stored in adipose tissue.
• Several hormones, including epinephrine, stimulate fat
mobilization when body cells need fatty acids for energy.
• Fat mobilization entails the hydrolysis of stored triglycerides
into fatty acids and glycerol which then enter the
bloodstream.
• In blood, mobilized fatty acids form a lipoprotein with the
plasma protein called serum albumin.
• Fatty acids transported to tissue cells that need them in this
form.
• Glycerol produced from triglyceride hydrolysis is water
soluble.
• Glycerol dissolves in blood.
• Glycerol is transported to cells that need it.
GLYCEROL METABOLISM
• Glycerol can be converted to dihydroxyacetone phosphate,
an intermediate of glycolysis.
• Glycerol can be converted to pyruvate and contribute to
cellular energy production.
• Pyruvate can be converted to glucose through
gluconeogenesis.
FATTY ACID OXIDATION
Activation Step:
• Before fatty acids can be catabolized, they must be activated
by conversion to fatty acyl CoA.
• The conversion to fatty acyl CoA is catalyzed by acyl CoA
synthetase.
FATTY ACID OXIDATION (continued)
• After activation, the fatty acid enters mitochondria and is
degraded in the fatty acid spiral via -oxidation.
• In the final step of -oxidation, the chain is broken between
the - and -carbons by the reaction with coenzyme A.
FATTY ACID OXIDATION (continued)
FATTY ACID OXIDATION (continued)
O
O
CH3(CH2)14-C-CH2-C-S-CoA
FATTY ACID OXIDATION (continued)
• Stearic acid:
• makes eight passes through -oxidation sequence.
• produces nine molecules of acetyl CoA.
• produces eight molecules FADH2.
• produces eight molecules of NADH.
FATTY ACID OXIDATION (continued)
• During -oxidation, the second carbon of the fatty acyl CoA
molecule is oxidized to a ketone.
• Each pass through the fatty acid spiral produces:
• one molecule acetyl CoA;
• one molecule NADH;
• and one molecule FADH2.
FATTY ACID OXIDATION (continued)
• In the last spiral, the four-carbon chain of butyryl CoA passed
through the -oxidation sequence, and produces:
• one molecule FADH2,
• one molecule NADH,
• and two molecules of acetyl CoA.
KEY NUMBERS FOR ATP CALCULATIONS
• Determine the number of acetyl CoA molecules:
number of fatty acid carbons
acetyl CoA 
2
• Determine the number of trips through the fatty acid spiral
(one less than the number of acetyl CoA molecules):
• Multipliers:
• every acetyl CoA = 10 ATP molecules
• every NADH = 2.5 ATP molecules
• every FADH2 = 1.5 ATP molecules
KEY NUMBERS FOR ATP CALCULATIONS
(continued)
• Example for 10-carbon fatty acid (five acetyl CoA molecules,
four trips through fatty acid spiral):
(5 acetyl CoA) × 10
(4 NADH + H+) × 2.5
(4 FADH2) × 1.5
Activation step
Total ATP
= 50 ATP
= 10 ATP
= 6 ATP
= −2 ATP
= 64 ATP
ENERGY FROM FATTY ACIDS
• To obtain energy from stearic acid:
• it is activated by a reaction with coenzyme A to form stearoyl
CoA, which requires the hydrolysis of ATP to AMP and PPi
and PPi to 2 Pi;
• stearoyl CoA passes through the -oxidation spiral to form:
• 9 molecules of acetyl CoA, which can enter citric acid
cycle and electron transport chain to produce 10 ATP
molecules per acetyl CoA;
• 8 molecules FADH2, which can enter the electron
transport chain to produce 1.5 ATP molecules per FADH2;
• and 8 molecules NADH, which can enter the electron
transport chain to produce 2.5 ATP molecules per NADH;
• One molecule of stearic acid yields 120 molecules of ATP upon
complete degredation.
ENERGY FROM FATTY ACIDS (continued)
• The amount of energy produced from stearic acid (C18):
ENERGY FROM FATTY ACIDS (continued)
• Fatty acids are more “energy dense” than carbohydrates.
Compound
Mass
ATP Produced
1 mol stearic acid (C18)
284g
120 mol
3 mol glucose (C18)
540g
96 mol
• On basis of equal numbers of carbons, lipids are nearly 25%
more efficient than carbohydrates as energy-storage
systems.
• On an equal-mass basis, lipids contain more than twice the
energy of carbohydrates.
• Lipids are more reduced than glucose (partially oxidized).
AMINO ACID METABOLISM
• The most important function of amino acids:
• is to provide building blocks for the synthesis of proteins in
the body.
• uses ~75% of amino acids in normal, healthy adults.
• The amino acid pool is the total supply of amino acids in the
body coming from digestion of food, degradation of tissue, and
synthesis in the liver.
• Protein turnover is when body proteins are hydrolyzed and
resynthesized.
• Turnover rate of proteins is measured as a half-life.
• Amino acids in excess of immediate body requirements are
not stored for later use, but degraded and the nitrogen atoms
are converted and excreted, while carbon skeletons are used
for energy production, synthesis of glucose, or conversion to
triglycerides.
AMINO ACID METABOLISM (continued)
AMINO ACID METABOLISM (continued)
AMINO ACID CATABOLISM
• The nitrogen of amino acids is either excreted or used to
synthesize other compounds.
• There are three stages to nitrogen catabolism:
1. Transamination
2. Deamination
3. Urea formation
AMINO ACID CATABOLISM (continued)
• Step 1: Transamination is the enzyme-catalyzed
(transaminase) transfer of an amino group to a keto acid.
• This process is also an important method in the biosynthesis
of nonessential amino acids (glutamate and aspartate)
from a variety of amino acids.
AMINO ACID CATABOLISM (continued)
• The following equations are specific examples of the transfer
of amino groups to -ketoglutarate. The carbon skeleton
remains behind and is transformed into a new -keto acid:
AMINO ACID CATABOLISM (continued)
• Step 2: Deamination is an oxidative process resulting in a
removal of an amino group.
• This reaction is the principle source of NH4+ in humans.
• This reaction is called oxidative deamination.
• This reaction is catalyzed by enzymes in the liver (amino acid
oxidases).
AMINO ACID CATABOLISM (continued)
• Step 3: Urea Formation via a metabolic pathway (urea
cycle) in which ammonia is converted to urea.
UREA CYCLE
UREA CYCLE (continued)
• After urea is formed, it diffuses out of liver cells into the
blood, the kidneys filter it out, and it is excreted in the urine.
• Normal urine from an adult contains 25-30 g of urea daily, but
exact amount varies with protein content of the diet.
• The direct excretion of NH4+ accounts for a small but
important amount of the total urinary nitrogen.
• It can be excreted with acidic ions, which helps kidneys
control the acid-base balance of body fluids.
FATE OF THE CARBON SKELETON
• The carbon skeletons of amino acids fall into two categories:
• glucogenic amino acids, which have a carbon skeleton
that can be metabolically converted to an intermediate of
glucose synthesis.
• ketogenic amino acids, which have a carbon skeleton
that can be metabolically converted to acetyl CoA or
acetoacetyl CoA.
AMINO ACID CATABOLISM (continued)
• The fates of ketogenic (green) amino acid carbon skeletons
and glucogenic (purple) amino acids:
ESSENTIAL AND
NONESSENTIAL AMINO ACIDS
• Note:
Essential amino acids cannot be synthesized by the body;
nonessential amino acids can be synthesized by the body.
AMINO ACID BIOSYNTHESIS
• A summary of amino acid biosynthesis:
AMINO ACID BIOSYNTHESIS (continued)
• The liver produces most of the amino acids the body can
synthesize (nonessential amino acids).
• The synthesis occurs from intermediates of the glycolysis
pathway and citric acid cycle.
• Tryosine is produced from the essential amino acid
phenylalanine:
AMINO ACID BIOSYNTHESIS (continued)
• Glutamate, alanine, and aspartate are synthesized from
-keto acids via reactions catalyzed by transaminases.
• Alanine is produced from pyruvate and glutamate:
AMINO ACID BIOSYNTHESIS (continued)
• Asparagine and glutamine are formed from aspartate and
glutamate by reaction of the side-chain carboxylate groups
with ammonium ions: