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Protein metabolism
The word metabolic means biochemical. The two types are called
anabolic and catabolic.
1- Anabolism or constructive metabolism: In this pathway many
small molecules are combined together to give a complex molecule. For
example the synthesis of proteins from amino acids is an anabolism
activity. During this energy is consumed and new cells are generated.
Insulin, testosterone and Estrogen are some anabolism hormones.
amino acids join together to make di peptides:
NH2CHRCOOH + NH2CHRCOOH -----˃ NH2CHRCONHCHRCOOH + H2O
Stages of anabolism:
There are three basic stages of anabolism:
Stage 1 production of precursors such as amino acids, monosaccharides
and nucleotides
Stage 2 use energy from ATP to turn the precursors into reactive form.
Stage 3 the assembly of these activated precursors into complex
molecules such as proteins, polysaccharides, lipids and nucleic acids.
2- Catabolism or destructive metabolism: In this pathway a large
molecule is decomposed to give many small molecules along with
energy. The breaking of a polysaccharide to simple glucose, breaking of
lipid to simple fatty acids and protein to amino acid are examples of
catabolism. Cortisol and Adrenalin are some examples for catabolism
hormones.
Protein Catabolism:
Proteins are complex polymers of amino acids. The sequence of amino
acids determine the nature and functional behavior of protein like in
DNA and RNA. In protein catabolism the proteins are hydrolyzed back
to amino acids.
Transamination:
Aminotransfer reaction between an amino acid and an alpha-keto acid.
Most amino acids are deaminated by transamination, a chemical
reaction that transfers an amino group to a ketoacid to form new amino
acids.
Transamination in biochemistry is accomplished by enzymes called
transaminases or aminotransferases. α-ketoglutarate acts as the
predominant amino group acceptor and produces glutamate as the new
amino acid.
Amino acid + α-ketoglutarate ↔ α-keto acid + Glutamate
Glutamate's amino group, in turn, is transferred to oxaloacetate in a
second transamination reaction yielding aspartate.
Glutamate + oxaloacetate ↔ α-ketoglutarate + aspartate
Urea Cycle
Urea cycle (also known as the ornithine cycle) is a cycle of biochemical reactions
occurring in many animals that produce urea ((NH2)2CO) from ammonia (NH3).
This cycle was the first metabolic cycle discovered (Hans Krebs and Kurt
Henseleit, 1932), five years before the discovery of the TCA cycle. In mammals,
the urea cycle takes place primarily in the liver, and to a lesser extent in the
kidney.
Function of urea cycle:
Organisms that cannot easily and quickly remove ammonia usually have to
convert it to some other substance, like urea or uric acid, which are much less
toxic. Insufficiency of the urea cycle occurs in some genetic disorders (inborn
errors of metabolism), and in liver failure. The result of liver failure is
accumulation of nitrogenous waste, mainly ammonia, which leads to hepatic
encephalopathy.
Urea Cycle Disorders
A urea cycle disorder is a genetic disorder caused by a mutation that results in a
deficiency of one of the five enzymes in the urea cycle. These enzymes are
responsible for removing ammonia from the blood stream. The urea cycle
involves a series of biochemical steps in which nitrogen, a waste product of
protein metabolism, is removed from the blood and converted to a compound
called urea in the blood. Normally, the urea is transferred into the urine and
removed from the body. In urea cycle disorders, the nitrogen accumulates in the
form of ammonia, a highly toxic substance, resulting in hyperammonemia
(elevated blood ammonia). Ammonia then reaches the brain through the blood,
where it can cause irreversible brain damage, coma and/or death.
Symptoms
Typically, the baby begins nursing well and seems normal. However, over time
the baby develops poor feeding, vomiting, and sleepiness, which may be so deep
that the baby is difficult to awaken. This usually occurs within the first week after
birth.
Symptoms include:
- Confusion
-Decreased food intake
-Dislike of foods that contain protein
-Increased sleepiness, difficulty waking up
-Nausea, vomiting
Exams and Tests
The health care provider will often diagnose these disorders when the child is still
an infant.
Signs may include:
-Abnormal amino acids in blood and urine
- Abnormal level of orotic acid in blood or urine
- High blood ammonia level
-Normal level of acid in blood
Tests may include.
-Genetic tests
-Liver biopsy
-MRI(magnatic resonance imagin) or CT scan(computerized axilla tomography)
Treatment
Limiting protein in the diet can help treat these disorders by reducing the amount
of nitrogen waste the body produces. (The waste is in the form of ammonia.).
Special low-protein infant and toddler formulas are available.
It is important that a provider guides protein intake. The provider can balance the
amount of protein the baby gets so that it is enough for growth, but not enough to
cause symptoms.
It is very important for people with these disorders to avoid fasting.
People with urea cycle abnormalities must also be very careful under times of
stress, such as when they have infections. Stress, such as a fever, can cause the
body to break down its own proteins. These extra proteins can make it hard for
the abnormal urea cycle to remove the byproducts.
Develop a plan with your provider for when you are sick to avoid all protein,
drink high carbohydrate drinks, and get enough fluids.
Most people with urea cycle disorders will need to stay in the hospital at some
point. During such times, they may be treated with medicines that help the body
remove nitrogen-containing wastes. Dialysis may help rid the body of excess
ammonia during extreme illness.
Hyperammonemia
Hyperammonemia is a metabolic condition characterized by elevated
levels of ammonia in the blood. Increased entry of ammonia to the brain
is a primary cause of neurologic disorders, such as congenital
deficiencies of urea cycle enzymes, hepatic encephalopathies, Reye
syndrome, several other metabolic disorders, and some toxic
encephalopathies.
Disorders of Amino Acid Metabolism
Phenylketonuria (PKU)
Phenylketonuria (PKU): is an inborn error of metabolism that results
in decreased metabolism of the amino acid phenylalanine , caused by
Phenylalanine hydroxylase deficiency, PAH deficiency.
Maple syrup urine disease
Maple syrup urine disease is caused by lack of the enzyme needed to
metabolize amino acids. By-products of these amino acids cause the
urine to smell like maple syrup. Infants with severe disease are treated
with dialysis. Some children with mild disease benefit from injections
of vitamin B1 (thiamin). After the disease has been brought under
control, children must always consume a special artificial diet that is
low in three amino acids (leucine, isoleucine, and valine).
Tyrosinemia
Tyrosinemia is caused by lack of the enzyme needed to metabolize
tyrosine. The most common form of this disorder mostly affects the
liver and the kidneys. Children with tyrosinemia are unable to
completely metabolize the amino acid tyrosine.
There are two main types of tyrosinemia:
type I and type II
Type I tyrosinemia is most common among children of FrenchCanadian or Scandinavian descent. Children with this disorder
typically become ill sometime within the first year of life with
dysfunction of the liver, kidneys, and nerves, resulting in irritability,
rickets, or even liver failure and death.
Type II tyrosinemia is less common. Affected children sometimes
have intellectual disability and frequently develop sores on the skin
and eyes. Unlike type I tyrosinemia, restriction of tyrosine in the diet
can prevent problems from developing.
Argininosuccinic acidemia (ASA)
In ASA, the body can’t remove ammonia or a substance called
argininosuccinic acid from the blood. Fewer than 1 in 100,000 babies
in the United States is born with ASA Babies with ASA who don’t
get treatment often die within the first few weeks of life.
Citrullinemia (CIT)
In CIT, the body has trouble breaking down amino acids and getting rid
of ammonia in the blood. For babies with CIT, the liver may not work
properly to help get rid of ammonia in the body. Fewer than 1 in
100,000 babies in the United States is born with CIT each year.
Health problems caused by CIT can include brain damage, intellectual
and developmental disabilities, liver problems and coma. Early
treatment can help prevent these problems. Milder forms of CIT may
not start until childhood or later.
Homocystinuria(HCY)
Homocystinuria is caused by lack of the enzyme needed to
metabolize homocysteine. In HCY, the body can’t break down the
amino acid homocysteine. Fewer than 1 in 100,000 babies is born
with HCY in the United States each year. If untreated, HCY can
cause problems with the blood, bones, eyes, heart and pancreas.
Babies with HCY may look healthy at birth, but symptoms usually
appear within the first year of life. Children with homocystinuria are
unable to metabolize the amino acid homocysteine.