Protein Prof. Dr.

Walaa Esmael Jassim

Amino Acids are the "building Blocks" of the body. It is organic molecules that
consist of a basic amino group (NH2), an acidic carboxyl group (―COOH), and an
organic R group (or side chain) that is unique to each amino acid. The term amino
acid is short for α-amino [alpha-amino] carboxylic acid. Each molecule contains a
central carbon (C) atom, called the α-carbon, to which both an amino and a
carboxyl group are attached. The remaining two bonds of the α-carbon atom are
generally satisfied by a hydrogen (H) atom and the R group. The formula of a
general amino acid is

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amino acids differ from each other in the particular chemical structure of
the R group. Proteins are of primary importance to the continuing functioning of
life on Earth. Proteins catalyze the vast majority of chemical reactions that occur in
the cell. They provide many of the structural elements of a cell, and they help to
bind cells together into tissues. Some proteins act as contractile elements to make
movement possible. Others are responsible for the transport of vital materials from
the outside of the cell (“extracellular”) to its inside (“intracellular”).
Many hormones are proteins. proteins control the activity of genes (“gene
expression”)Proteins, in the form of antibodies, protect animals from disease and,
in the form of interferon, and in the form of Interferons which are proteins that
are part of natural defenses (IFNs) produced by a variety of cells in the
inflammatory response to infections. Their production is triggered by the immune
system in response to pathogens or cytokines. Interferons (IFNs) in the body's are
the first line of antiviral defense —they are secreted by host cells in response to
virus infection. IFNs block virus replication at many levels. Unlike fats and
carbohydrates, amino acids are not stored by the body • Therefore, amino acids
must be obtained from the diet, synthesized de novo or produced from normal
protein degradation • The first phase of catabolism involves the removal of α-
amino groups (usually by transamination and subsequent oxidative deamination)
forming ammonia and the corresponding α-keto acid • In the second phase of
amino acid catabolism, the carbon skeletons of the αketo acids are converted to
common intermediates of energy producing, metabolic pathways. These
compounds can be metabolized to CO2 and water, glucose, fatty acids or ketone
bodies by the central pathways of metabolism

Protein metabolism
Nitrogen enters the body in a variety of compounds present in foods, the most
important being amino acids contained in dietary proteins • Nitrogen leaves the
body as urea, ammonia and other products derived from amino acid metabolism •
The role of body protein in these transformations involves two important concepts:
the amino acid pool and protein turnover
Protein metabolism refers to the processes by which proteins are synthesized,
broken down, and

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converted into other molecules within the body. Proteins play crucial roles in
various biological functions, including structural support, enzymatic activity,
immune response, and cell signaling.
Much of the body is made of protein, and these proteins take on a myriad of forms:
[Link] represent cell signaling receptors, signaling molecules, structural members,
enzymes, intracellular trafficking components, extracellular matrix scaffolds, ion
pumps, ion channels, oxygen and CO2 transporters (hemoglobin).
[Link] is protein in bones (collagen), muscles, and tendons;
3. the hemoglobin that transports oxygen; and enzymes that catalyze all
biochemical
reactions.
[Link] is also used for growth and repair.
Amid all these necessary functions, proteins also hold the potential to serve as a
metabolic fuel source. Proteins are not stored for later use, so excess proteins must
be converted into glucose or triglycerides, and used to supply energy or build
energy reserves. Although the body can synthesize proteins from amino acids, food
is an important source of those amino acids, especially because humans cannot
synthesize all of the 20 amino acids used to build proteins.
The digestion of proteins begins in the stomach. When protein-rich foods enter the
stomach, they are greeted by a mixture of the enzyme pepsin and hydrochloric
acid (HCl; 0.5 percent). The latter produces an environmental pH of 1.5–3.5 that
denatures proteins within food. Pepsin cuts proteins into smaller polypeptides and
their constituent amino acids. When the food-gastric juice mixture (chyme) enters
the small intestine, the pancreas releases sodium bicarbonate to neutralize the
HCl. This helps to protect the lining of the intestine. The small intestine also
releases digestive hormones, including secretin and CCK, which stimulate
digestive processes to break down the proteins further. Secretin also stimulates the
pancreas to release sodium bicarbonate. The pancreas releases most of the
digestive enzymes, including the proteases trypsin, chymotrypsin, and elastase,
which aid protein digestion. Together, all of these enzymes break complex proteins
into smaller individual amino acids, which are then transported across the intestinal
mucosa to be used to create new proteins, or to be converted into fats or acetyl
CoA and used in the Krebs cycle.
Urea cycle

The urea cycle (also known as the ornithine cycle) is a cycle

of biochemical reactions that produces urea (NH2)2CO from ammonia (NH3).

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The urea cycle converts highly toxic ammonia to urea for excretion. The urea cycle
takes place primarily in the liver and, to a lesser extent, in the kidneys.

Function
Amino acid catabolism results in waste ammonia. All animals need a way to
excrete this product. Most organisms, excrete ammonia without converting
it. Organisms that cannot easily and safely remove nitrogen as ammonia convert it
to a less toxic substance, such as urea, via the urea cycle, which occurs mainly in
the liver. Urea produced by the liver is then released into the bloodstream, where it
travels to the kidneys and is ultimately excreted in urine. The urea cycle is essential
to these organisms, because if the nitrogen or ammonia is not eliminated from the
organism it can be very detrimental. In species including birds and most insects,
the ammonia is converted into uric acid or its urate salt, which is excreted in solid
form. Further, the urea cycle consumes acidic waste carbon dioxide by combining
it with the basic ammonia, helping to maintain a neutral pH.

What happens when the urea cycle goes wrong?

If there is a problem with the urea cycle, then the level of ammonia in the blood
will rise, causing hyperammonemia. Ammonia is able to cross the barrier between
the bloodstream and the brain. Once it enters the brain, it can stop the TCA cycle
by depleting one of the metabolites, α-ketoglutarate. This means that these brain
cells cannot make energy, ultimately leading to their death. This eventually will
lead to neurological problems, which can be as severe as irreversible brain damage.
Problems can arise as a result of damage to the liver (cirrhosis) or by an inherited
defect in one of the enzymes. In both cases, the level of ammonia rises with the
potential consequences previously detailed. Inherited urea cycle defects are part of
“inborn errors in metabolism”, and are known as “urea cycle disorders.” Symptoms
are usually present in newborns around 24-48 hours after birth. Treatment for
hyperammonemia consists of removing protein from the diet, removing the excess
ammonia and supplementing with molecules of the urea cycle which are missing.
Also, sodium benzoate and sodium acetate can be used to form ammonia-
containing compounds that can be excreted through feces. Antibiotics can be used
to eliminate the ammonia-forming gut bacteria. Uremia is the condition of having
high levels of urea in the blood. Urea is one of the primary components of urine. It
can be defined as an excess in the blood of amino acid and protein metabolism end
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products, such as urea and creatinine, which would normally be excreted in the
urine

Disorders of amino acid metabolism

Twenty amino acids, including nine that cannot be synthesized in humans and must
be obtained through food, are involved in metabolism. Amino acids are the
building blocks of proteins; some also function or used in to synthesize important
molecules in the body such as neurotransmitters, hormones, pigments, and oxygen-
carrying molecules. Each amino acid is further broken down into ammonia, carbon
dioxide, and water. Disorders that affect the metabolism of amino acids include
phenylketonuria, tyrosinemia, homocystinuria, non-ketonic hyperglycinemia, and
maple syrup urine disease. These disorders are autosomal recessive, and all may be
diagnosed by analyzing amino acid concentrations in body fluids.

Phenylketonuria (PKU) is an inborn error of metabolism that results in decreased

metabolism of the amino acid phenylalanine. It is caused by decreased activity
of phenylalanine hydroxylase (PAH), an enzyme that converts the amino
acid phenylalanine to tyrosine, a precursor of several important hormones and skin,
hair, and eye pigments. Like tyrosine, phenylalanine is also a precursor for
catecholamines including tyramine, dopamine, epinephrine, and norepinephrine.

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Decreased PAH activity results in accumulation of phenylalanine and a decreased
amount of tyrosine and other metabolites. High levels of phenylalanine in the
blood in turn result in progressive developmental delay, behaviors disturbances,
and seizures. Treatment with foods low in phenylalanine and protein can reduce
phenylalanine levels to normal. However, rare cases of PKU that result from
impaired metabolism of biopterin, an essential cofactor in the phenylalanine
hydroxylase reaction, may not consistently respond to therapy.
Classic tyrosinemia is caused by a deficiency of the last enzyme in tyrosine
catabolism. Features of classic tyrosinemia include severe liver disease,
unsatisfactory weight gain, peripheral nerve disease, and kidney defects.

Homocystinuria is caused by a defect in cystathionine beta-synthase (or β-

synthase), an enzyme that participates in the metabolism of methionine, which
leads to an accumulation of homocysteine. Symptoms include a pronounced flush
of the cheeks, a tall, thin frame, lens dislocation, vascular disease, and thinning of
the bones (osteoporosis. Approximately 50 percent of persons with homocystinuria
are responsive to treatment with vitamin B6 (pyridoxine. Therapy with folic
acid, betaine (a medication that removes extra homocysteine from the body),
aspirin, and dietary restriction of protein and methionine also may be of benefit.

Maple syrup urine disease, inherited metabolic disorder

involving leucine, isoleucine, and valine (a group of branch chain amino acids).
Normally, these amino acids are metabolized, step by step, by a number of
enzymes, each of which is specific for each step in the metabolism of each amino
acid. One of the metabolic steps consists of the decarboxylation of the α-keto acids
of leucine, isoleucine, and valine, respectively. In maple syrup disease, this
particular step is blocked because of defective decarboxylating enzymes. As a
result, leucine, isoleucine, and valine are found to increase in concentration in
the blood plasma and to overflow, together with their respective α-keto acids, into
the urine, which takes on a distinctive odor resembling that of maple syrup. Other
signs of the disorder that are evident during the first few weeks of life include:
poor feeding, irregular respiration, heightened muscular tension, and rigid arching
of the back; the nervous system is also severely impaired. Affected infants die
within several weeks unless treated. Effective treatment depends upon a diet low in
leucine, isoleucine, and valine.

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Non-ketotic hyperglycinemia is characterized by seizures, low muscle tone,
hiccups, breath holding, and severe developmental impairment. It is caused by
elevated levels of the neurotransmitter glycine in the central nervous system, which
in turn are caused by a defect in the enzyme system responsible for cleaving the
amino acid glycine. Drugs that block the action of glycine (e.g.,
dextromethorphan), a low-protein diet, and glycine-scavenging medications (e.g.,
sodium benzoate) may ease symptoms, but there is no cure for this severe
condition.