Amino Acid Disorders

An account of amino acid metabolism disorders in humans beings with an emphasis of the underlying molecular defects

Amino acids are monomers which join together to form a protein and are multi-functional in the human body. However, defects in amino acid metabolism occur which cause a numerous amount of disorders in humans.

One of the most common amino acid disorders is phenylketonuria (PKU). There are two types of PKU and they are known as the type 1 and the type 2. The cause of type 1PKU is the fact that the phenylalanine hydroxylase enzyme is not present or that it is defective. The cause pf PKU type 2, which hardly occurs is to do with the tetrahydrobioprotein co factor. PKU causes the accumulation of phenylalanine in all of body’s fluids. This accumulation is due to the fact phenylalanine is not able to convert into the tyrosine. According to Biochemistry, 5th Edition (2002), J.M. Berg, J. L. Tymoczko and L. Stryer, Ch 23 Protein Turnover and Amino Acid Catabolism, “three quarters of phenylalanine converted into Tyrosine and the other quarter incorporated into proteins.” In PKU patients the major diversion pathway is jammed causing the phenylalanine to increase as much as twenty times, as a normal person, in blood. As an added unfortunate bonus some PKU patients tend to expel large amount of phenylpyruvate in their urine. Such patients have a brain weight below average and suffer mental retardation. A simple test can be carried out to check whether phenylpyruvate is present in the urine by simply adding Iron Chloride (FeCl ) to the urine. If it is present a urine colour change occurs from yellow to olive green. PKU suffers seem to be normal at birth but, if left untreated their condition can severely depreciated before their first birthday. There is a method of therapy used to treat PKU level 1 which is to put the sufferer on a low or lack of phenylalanine diet. PKU level 2 is hard to treat due to biopterin metabolism defects.

Another amino acid metabolism defective disorder is Canavan’s disease, which is caused by the absence of the enzyme N-acetylaspartate acylase. The deficiency of this enzyme causes N-acetylaspatic acid (NAA) to accumulate in the brain. This build up causes myelin to be obliterate due to an unequal level of chemicals. The myelin becomes springy and results in the symptoms of Canavan’s disease to present themselves. It mainly affects children in the Middle East and Central Europe. There are two diagnostic methods of finding out if a patient has Canavan’s disease. One is to measure the levels of N-acetylaspartate acylase in the cells of the skin; if the levels are below the norm then the patient has the disease. The second method is screening both potential parents to see if they are carriers or contain the gene. If there is a risk to the child then counselling is offered to help them plan for its future.

Another disease is branched-chain amino aciduria or more commonly known Maple Syrup urine disease, (MSUD). It is caused by an inability to metabolise the enzyme leucine, isoleucine and valine. A prominent symptom is the fact that the patient’s urea smells like maple syrup hence its name. Other symptoms include no appetite, vomiting, spasms, exhaustion of which generally as acidosis occurs in the primary week of the disease. In severe conditions patients may go into a coma. New born children are more susceptible to the disease so if left untreated during their first few weeks of life they will die. It is highly simply to PKU as it is also a urinary disease and can cause mental retardation. There are several tests available to see if a person suffers from MSUD. The more common one being to simply to check if the patient contains high levels of the amino acids leucine, isoleucine and valine and if ketones are present in their urine and plasma. There are several treatments but the more immediate method is to remove branched chain amino acids from the patient’s diet by removing protein. Increased dosages of sugar and fat are given to the patient to accelerate the rate of protein synthesis and to avoid him/her to suffer dehydration.

The urea cycle is an important mechanism in the human body. It converts toxic ammonia into a non toxic substance urea. However, errors can occur to produce metabolic disorders. One such disorder is argininosuccinic aciduria, which is a recessive disorder. Nitrogen is not being able to be converted into ammonia this is because the urea cycle is a closed system and if one passage is blocked there is no release for the substances, so they continue to accumulate, (Diagram of normal and abnormal urea cycle is on a separate page). In this case there is no arginine being made which is an important factor in the production of urea and ornithine. Symptoms are obviously a continuous build up of ammonia causing hyperammonemia combined with no desire to eat, continuous