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1Dr. Diala Abu-Hassan00
Protein and Amino Acid
Metabolism
All images were taken from McMurry et al
except where noted
Dr. Diala Abu-Hassan, DDS, PhD
Nursing
Digestion of Protein
2Dr. Diala Abu-Hassan
Trypsin
Chymotrypsin
Carboxypeptidase
pH 1-2
pH 7-8
Amino Acid Metabolism
3Dr. Diala Abu-Hassan
Amino Acid Metabolism
4Dr. Diala Abu-Hassan
Each of the 20 amino acids is degraded via its own unique pathway
General scheme for amino acid catabolism:
• Removal of the amino group
• Use of nitrogen in synthesis of new nitrogen compounds
• Passage of nitrogen into the urea cycle
• Incorporation of the carbon atoms into compounds that can enter the
citric acid cycle
Amino Acid Catabolism: The Amino Group
5Dr. Diala Abu-Hassan
Transamination The interchange of the amino group of an amino acid and the α-keto group of an acid.
Glutamate fate
6Dr. Diala Abu-Hassan
The glutamate from transamination serves as an amino group carrier.
Glutamate provides amino groups for the synthesis of new amino acids
Most of the glutamate formed is recycled to regenerate α-ketoglutarate
(oxidative deamination)
Oxidative deamination oxidatively removes the glutamate amino group as
ammonium ion and recycle α -ketoglutarate:
To urea cycle to be eliminated
in the urine as urea
Pathway of nitrogen from an amino acid to urea
7Dr. Diala Abu-Hassan
The fate of carbons and nitrogens in from amino acid metabolism
8Dr. Diala Abu-Hassan
Our bodies do not store nitrogen-containing compounds and
ammonia is toxic to cells.
The amino nitrogen must either:
1. Be incorporated into urea and excreted
2. Be used in the synthesis of new nitrogen-containing compounds
Carbon from amino acids enter Kreb’s cycle and the excess is
stored as TAGs (via lipogenesis), glycogen (via gluconeogenesis
and glycogen synthesis), or converted to ketone bodies.
(Nitric oxide (NO, a chemical messenger), Hormones, Neurotransmitters, Heme, Purine and pyrimidine bases (for nucleic acids), Nicotinamide (in NAD+ and NADP+))
Amino Acid Catabolism: The Carbon Atoms
9Dr. Diala Abu-Hassan
The carbon atoms of amino acids arrive by
distinctive pathways at pyruvate, acetyl-SCoA,
or one of the citric acid cycle intermediates.
All amino acid carbons can be used to generate
energy either by:
1. The citric acid cycle
2. Gluconeogenesis pathway to form glucose
3. Ketogenesis pathway to form ketone bodies
Amino Acid Catabolism: The Carbon Atoms
10Dr. Diala Abu-Hassan
Both ketogenic and glucogenic amino acids are able to enter
fatty acid biosynthesis via acetyl-SCoA
The Urea Cycle
11Dr. Diala Abu-Hassan
Urea cycle is the cyclic biochemical pathway that produces urea
for excretion (the conversion of ammonium ion to urea). The cycle
takes place in the liver)
Ammonia is highly toxic and large amount of water is needed to
dilute it, thus it is converted to non-toxic urea via urea cycle.
An energy-rich
phosphate-like ATP
In the mitochondrial matrix:
From oxidative
deamination of amino acids
From CO2 from the Kreb’s cycle
The Urea Cycle
12Dr. Diala Abu-Hassan
STEPS 1 and 2:
Building Up a Reactive
Intermediate
STEPS 3 and 4:
Cleavage and Hydrolysis
of the Step 2 Product
The Net Result of the Urea Cycle
13Dr. Diala Abu-Hassan
Formation of urea from the carbon of CO2 and NH4+ and one nitrogen
from the amino acid aspartate, followed by biological elimination
through urine.
Breaking of four high-energy phosphate bonds to provide energy
Production of the citric acid cycle intermediate, fumarate
Diseases associated with ammonia
14Dr. Diala Abu-Hassan
Hereditary diseases resulting high levels of ammonia in the
blood (hyperammonemia) cause vomiting in infancy, lethargy,
irregular muscle coordination (ataxia), and mental retardation.
Immediate treatment consists of transfusions, blood dialysis
(hemodialysis), and use of chemical agents to remove
ammonia.
Long-term treatment requires a low-protein diet and frequent
small meals to avoid protein overload
Essential Amino Acids
15Dr. Diala Abu-Hassan
Humans are able to synthesize about half of the 20 amino acids found in proteins
(nonessential amino acids) because they do not have to be supplied by our diet.
The essential amino acids are synthesized only by plants and microorganisms.
Biosynthesis of Nonessential Amino Acids
16Dr. Diala Abu-Hassan
Reductive deamination is the conversion of an α-keto acid
to an amino acid by reaction with NH4+
All of the nonessential amino acids derive their amino groups
from glutamate
Biosynthesis of Nonessential Amino Acids
17Dr. Diala Abu-Hassan
Diseases associated with AA synthesis Phenylketonuria (PKU)
18Dr. Diala Abu-Hassan
Failure to convert phenylalanine to tyrosine causes PKU
PKU causes mental retardation by the second month of life
Treatment consists of a diet low in phenylalanine by eliminating
meat and using low-protein grain products.
Foods sweetened with aspartame (a derivative of phenylalanine)
should be avoided.
Diseases-Gout
19Dr. Diala Abu-Hassan
Gout is a severely painful condition
caused by the precipitation of sodium urate crystals in joints
Anything that increases the
production of uric acid or
inhibits its excretion in the urine is a possible cause of gout