Metabolic Pathways for Lipids and Amino Acids
CHAPTER 24
HOW DO WE DIGEST THINGS THAT AREN’T CARBS?
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Lipids  fatty acids and glycerol
Proteins  amino acids
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Gives us the nitrogen to synthesize nitrogen-containing compounds in
our cells (new proteins and nucleic acids)
Both categories are further broken down in enzymatic reactions
from there.
A. DIGESTION OF TRIACYLGLYCEROLS
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Adipocytes = fat cells that compose our adipose tissue
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These store triacylglycerols
Body fat is our major source of stored energy
First step of dietary fat digestion: in the small intestine, fat
globules mix with bile salts, and emulsification occurs.
Second step of dietary fat digestion: pancreatic lipases
hydrolyze the triacylglycerols to yield monoacylglycerols and
free fatty acids.
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These products get reabsorbed through the lining of the small intestine
and recombine once again to form triacylglycerols, then combine with
proteins to form a lipoprotein called a chylomicron.
Where are all these internal organs, anyway?
CHYLOMICRONS
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Chylomicrons are transported through the bloodstream (now
water soluble!) and can be carried whereever they are needed.
MOBILIZATION OF FAT STORES
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Used as energy when blood glucose is low and glycogen stores
are depleted
Fat mobilization: triacylglycerols in the adipose tissue are
broken down to fatty acids and glycerol
In the next sets of slides, we’ll learn how the glycerol and the
fatty acids get processed once they’re broken apart
Activated by the hormones glucagon or epinephrine
METABOLISM OF GLYCEROL
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Gets metabolized in the liver
Glycerol is converted to dihydroxyacetone phosphate in two
steps, which we will not memorize, but this compound feeds
into glycolysis and gluconeogenesis.
B. OXIDATION OF FATTY ACIDS
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Yields a lot of energy!
Metabolism of fatty acids: beta (b) oxidation, which removes
chunks of two carbons at a time.
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Each two carbon chunk is degraded into an acetyl-CoA unit, which enters
the citric acid cycle.
And, the length of the fatty acid determines the number of times the
cycle repeats itself.
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For instance… myristic acid = 14 carbons = produces 7 acetyl-CoA groups = goes
through cycle 6 times
UNSATURATED FATTY ACIDS: WHAT’S THE
DIFFERENCE?
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Beta oxidation: applies to saturated fatty acids with an even
number of carbons. But many things we eat contain
unsaturated fatty acids.
How are these processed?
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A cis fatty acid is turned into a trans fatty acid via an isomerase
Then, a hydration reaction adds water across the double bond.
C. ATP AND FATTY ACID OXIDATION
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Each cycle of beta oxidation yields one NADH, one FADH2, and
one acetyl-CoA.
So, if you have a saturated fatty acid containing 16 carbons,
what would be the NADH/FADH2 yield?
D. KETOGENESIS AND KETONE BODIES
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When we don’t have enough carbohydrates to meet our energy
needs, the body will break down stored fats.
However, the breakdown of large amounts of fat will cause
acetyl-CoA molecules to accumulate in the liver. These
molecules will combine to form ketone bodies through the
ketogenesis pathway.
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Ketone bodies, once produced in the liver, are then transported to cells
in the heart, brain, and skeletal muscle. Conversion back to acetyl-CoA
generates small amounts of energy.
Sometimes ketone bodies are not completely metabolized –
leading to ketosis – lowers pH of the blood, causes breathing
difficulties.
E. FATTY ACID SYNTHESIS
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Occurs when the body has met all of its energy needs and there
is acetyl-CoA left over.
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In other words… a process a lot of us try to avoid, and a process that
has created a multi-billion dollar industry!
Called lipogenesis
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Overall: two carbon acetyl units are linked together to form palmitic acid
(a 16-carbon fatty acid)
Longer or shorter fatty acids may be formed by either stopping the
process short, or special enzymes that can continue the process longer
REGULATION OF FATTY ACID SYNTHESIS
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Takes place primarily in adipose tissue – site of formation and
storage of triglycerides
When blood glucose is high, insulin moves glucose into the
cells.
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Once inside the cell, insulin stimulates glycolysis and pyruvate oxidation,
which provides acetyl-CoA for synthesis of fatty acids
F. DIGESTION OF PROTEINS
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Why do proteins get digested?
Provide amino acids for synthesis of new proteins in the body
 Provide N atoms for synthesis of compounds such as nucleotides
Our major energy sources are carbohydrates and lipids, but when they are
not available, proteins can be used as an energy source
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PROCESS OF PROTEIN DIGESTION
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Stage 1: the stomach
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Stage 2: the small intestine
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HCl released by glands creates an acidic environment (pH 2). Denatures
proteins, activates enzymes that begin to hydrolyze peptide bonds
Polypeptides from the stomach move into the small intestine. Proteolytic
enzymes (such as trypsin and chymotrypsin) complete the hydrolysis of
the peptides into individual amino acids.
Then, the individual amino acids are absorbed through the
intestinal walls into the bloodstream. From here, they get
transported to the cells.
PROTEIN TURNOVER
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Or, proteins do not live forever in our bodies!
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Old proteins are constantly being replaced with new ones.
The process of synthesizing proteins and breaking them down = protein
turnover
For example, insulin has a half-life of 10 minutes, and hemoglobin has a
half-life of 120 days
If a protein is damaged and/or ineffective, it is also degraded
and replaced
The body cannot store nitrogen, so the excess gets excreted as
urea
DOES OUR BODY OBTAIN ENERGY FROM AMINO
ACIDS?
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It wouldn’t be the first choice.
Normally, only about 10% of the body’s energy needs is
supplied by amino acids.
However, under conditions of fasting or starvation, when
carbohydrate and fat stores are exhausted, amino acids are
used as an energy source.
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If these conditions persist for a long time, breakdown of body proteins
can lead to a destruction of essential body tissues.
G. DEGRADATION OF AMINO ACIDS
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First, the a-amino group is removed, yielding a keto acid.
This keto acid can be converted into an intermediate which can
feed into other metabolic pathways.
Most of the amino groups get converted to urea.
Degradation of amino acids primarily occurs in the liver.
H. UREA CYCLE
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What happens to all of the ammonium ions resulting from
deamination of amino acids?
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A pathway called the urea cycle converts them to urea, which is
transported to the kidneys to form urine.
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The ammonium groups are toxic if they are allowed to accumulate.
In a typical day, an adult will excrete about 25-30 g of urea in the urine –
moreso if the diet is high in protein
Occurs in the liver cells
J. FATES OF THE CARBON ATOMS FROM AMINO ACIDS
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The rest of the amino acid is sent into the citric acid cycle or
another metabolic pathway.
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If the amino acid skeleton has 3 carbons, it can be converted to
pyruvate.
If they have 4 or 5 carbons, they can be converted to another
intermediate in the citric acid cycle (oxaloacetate, or a-ketoglutarate).
K. SYNTHESIS OF AMINO ACIDS
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Humans (unlike bacteria) can only synthesize 10 of the 20
naturally occurring amino acids.
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The ones that we can synthesize are called nonessential amino acids
The ones that we cannot synthesize – in other words, we need to
consume them – are called essential amino acids
Some amino acids require merely a simple one-step synthesis
(a transamination); others require a multistep reaction. We
will not memorize the steps for this class; just be aware that
there are different pathways for the different amino acids.