WEEK 14: Protein Metabolism

Protein Metabolism

 is the chemical cycle of breaking down protein (catabolism) and using

the components to synthesize new molecules (anabolism) to be used in
the body.
 Dietary proteins are first broken down to individual amino acids by
various enzymes and hydrochloric acid present in the stomach. These
amino acids are absorbed into the bloodstream to be transported to
the liver and onward to the rest of the body.
 Protein Metabolism occurs in liver.
 Protein Catabolism
o AMINO ACIDS METABOLISM
 Amino Acids Catabolism
 Amino Acids Biosynthesis
 Specialized Products
 Protein Anabolism
o REPLICATION
o TRANSCRIPTION
o TRANSLATION

PROTEINS
 Amino acids are the building blocks for proteins, they provide C and N
for the synthesis of other biomolecules, and they are also sources of
energy (4 Cal/g).
 The most important function of amino acids (about 75% of amino acid
utilization) is to provide building blocks for the synthesis of proteins in
the body.

AMINO ACID POOL

 The maintenance of body proteins must occur constantly because

tissue proteins break down from normal wear and tear, from injuries,
and from diseases.
 The amino acids that are used in this maintenance come from the
amino acid pool of the body.
 These amino acids can come from:
 proteins that are eaten and hydrolyzed during digestion
 the body’s own degraded tissues
 the synthesis in the liver of certain amino acids.

PROTEIN TURN OVER and HALF-LIFE

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  The process in which body proteins are continuously hydrolyzed and
resynthesized is called protein turnover.
 The turnover rate, or life expectancy, of body proteins is a measure of
how fast they are broken down and resynthesized, expressed as a
half-life.
 The half-life of liver proteins is about 10 days: over a 10-day period,
half the proteins in the liver are hydrolyzed
o Plasma proteins = 10 days
o Hemoglobin = 120 days
o Muscle protein = 180 days
o Collagen = as high as 1000 days
o Enzyme and polypeptide hormones = as short as a few minutes.
o Insulin = 7-10 minutes

OTHER COMPOUNDS FROM AMINO ACIDS

 The frequent turnover of proteins allows the body to continually renew
important molecules and respond to changing needs.
 There is also a constant draw on the amino acid pool for the synthesis
of other N-containing biomolecules, such as the bases in DNA and RNA,
the heme in hemoglobin and myoglobin, the amino alcohols in
phospholipids, and neurotransmitters.

AMINO ACID METABOLIC PATHWAYS

 Amino acids in excess of immediate body requirements cannot be
stored for later use.
 The N atoms are converted to either ammonium ions, urea, or uric
acid (depending on the organism), and excreted.
 Their carbon skeletons are converted to pyruvate, acetyl CoA, or one
of the intermediates in the citric acid cycle and used for energy
production, the synthesis of glucose through gluconeogenesis, or
conversion to triglycerides.

AMINO ACID CATABOLISM

 The Fate of Nitrogen Atoms
 The N atoms in amino acids are either excreted or used to synthesize
other N-containing compounds
 There are three stages in nitrogen catabolism:
o Stage 1: Transamination

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 In the tissues, amino groups freely move from one amino acid
to another, under the influence of enzymes called amino
tranferases or trans aminases.
A key reaction for amino acids undergoing catabolism is a
transamination involving the transfer of amino groups to α-
ketoglutarate. The carbon skeleton of the amino acid remains
behind as an α -keto acid:
The net effect of this reaction is to exchange the NH3 + on
the amino acid with a =O.
Another important example of transamination is the
production of aspartate, which is used in Stage 3, urea
formation, from the transfer of an amino to oxaloacetate:
This process is an important method for the biosynthesis of
the nonessential amino acids: glutamate and aspartate from
a variety of other amino acids.
o Stage 2: Deamination
This phase of amino acid catabolism uses the glutamate
produced in Stage 1. The enzyme glutamate dehydrogenase
catalyzes the removal of the amino group as an ammonium
ion and regenerates α- ketoglutarate, which can participate in
transamination again.
This reaction is the principal source of NH4 + (ammonium) in
humans.
Because the deamination results in the oxidation of
glutamate, it is called oxidative deamination.
The NADH produced in this stage enters the electron transport
chain and eventually produces 2.5 ATP molecules.
Other amino acids can be catabolized by oxidative
deamination in the liver by enzymes called amino acid
oxidases.
o Stage 3: Urea Formation
The ammonium ions released by the glutamate
dehydrogenase in Step 2 are toxic and must be prevented
from accumulating. In the urea cycle, which only occurs in
the liver, NH4 + is converted to urea, which is less toxic, and
can be allowed to concentrate until it is excreted in urine.
The urea cycle process NH4 + in the form of carbamoyl
phosphate, the fuel for the urea cycle. This compound is
synthesized in the mitochondria from NH4 + and HCO3 -
The net reaction for carbamoyl phosphate formation and the
urea cycle is:
After urea is formed, it diffuses out of liver cells and into the
blood. It is then filtered out by the kidneys, and excreted in
the urine.

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 Normal urine from an adult usually contains about 23-30 g of
urea daily, although this varies with the protein content of
the diet.
The direct excretion of NH4 + accounts for a small but
important amount of the total urinary nitrogen.
The excretion of ammonium along with acidic ions is a
mechanism that helps the kidneys to control the acid-base
balance of body fluids.

THE FATE OF THE CARBON SKELETON

 After the amino group is removed by transamination or oxidative
deamination, the remaining amino acid carbon skeleton undergoes
catabolism and is converted into one of several products.
 After the amino group is gone, the skeletons of all 20 amino acids are
degraded into either pyruvate, acetyl CoA, acetoacetyl CoA (which is
degraded to acetyl CoA), or various substances that are intermediates
in the citric acid cycle.
 All these degraded forms of the carbon skeletons are a part of or can
enter the citric acid cycle, and thus may be very important in the
production of energy.

AMINO ACID BIOSYNTHESIS

 NONESSENTIAL AMINO ACIDS
o The liver produces most of the amino acids that the body can
synthesize. Amino acids that can be made in the amounts
needed by the body are called nonessential amino acids,
because they do not need to be obtained from the diet.
 ESSENTIAL AMINO ACIDS
o The essential amino acids are cannot be made in large enough
amounts and must be obtained from the diet.

Biosynthesis of Nonessential Amino Acids

 The key starting materials for the synthesis of 10 nonessential amino
acids are intermediates in glycolysis and the citric acid cycle:


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 Tyrosine is produced from the essential amino acid phenylalanine:
 Three nonessential amino acids (glutamate, alanine, and aspartate)
are synthesized from a-keto acids via transamination:
 The transaminases adjust the relative proportions of amino acids to
meet the needs of the body, since most of our diets do not contain
amino acids in the exact proportions needed by the body.
 Asparagine and glutamine are formed from aspartate and glutamate
by reaction of the side-chain carboxylate groups with ammonium ions:
 The synthesis of arginine, cysteine, glycine, proline, and serine are
considerably more complex.