Contact: to feature here

Thread Rating:
  • 0 Vote(s) - 0 Average
  • 1
  • 2
  • 3
  • 4
  • 5
Inborn Errors of Amino Acids Metabolism
Metabolism involves all the biochemical reactions that take place in the cells of organisms. Metabolism is divided into anabolism and catabolism. Catabolism is the breakdown of organic substances to produce energy while anabolism is the biosynthesis of complex organic materials with the expenditure of energy. Proteins, lipids and carbohydrates are the major substrates for catabolism. These biochemical pathways are very integral in the body functioning. There are different enzymes that are involved in these anabolic and catabolic and anabolic pathways. Any defectiveness in these enzymes in all these enzymatic reactions results into metabolic disorders. Metabolic diseases can either be classified as either inherited or acquired. Inherited disorders are also known as inborn errors of metabolism or congenital metabolic diseases.

Amino acids are building blocks of proteins which are made of carbon, hydrogen, oxygen and nitrogen. Biosynthesis or break down of these amino acids yield different products that are important in the body. Inborn errors of amino acid metabolism are as a result of accumulation of toxic metabolic products in the body system or as a result of inefficient breakdown of amino acids and proteins (Lehninger, 2008). There are different inborn errors of amino acid metabolism which include; Medium-chain-acyl-CoA dehydrogenase (MCAD), Maple syrup urine disease, Hereditary tyrosinemia, Arginosuccinic aciduria, Transient hyperammonemia of the newborn, and Ornithine transcarbamylase deficiency.

Tyrosinemia is an inborn error disorder that is as a result of ineffective breakdown of tyrosine. Tyrosine is a polar nonessential amino acid that is coded by UAC or UAU. It is caused by the deficiency of enzymes that break down the amino acid (Lehninger, 2008). Tyrosine catabolism is as shown in the schematic diagram below;

There are three types of tyrosinemia. They include tyrosinemia type I, type II and type III which are caused by deficiency of specific different enzymes. Tyrosinemia type I is a heritable condition that occurs in autosomal recessive pattern and is caused by the deficiency of the enzyme p-hydroxyphenylepyruvic acid oxidase and fumarylacetoacetate hydrolase. It is a very common disorder in Quebec in Canada. This disease is the most severe of the three tyrosinemia conditions. This enzyme takes part in the last stage of tyrosine catabolism where it catalyzes the breakdown of fumarylacetoacetate to fumarate.

Deficiency of fumarylacetoacetate hydrolase leads to increased amounts of fumarylacetoacetate in the hepatocytes which translates to inhibition of previous tyrosine breakdown processes. This leads to the accumulation of tyrosine in the body which causes dermatologic problems. This condition manifests itself in early months of life and affects the kidneys and the liver. It leads to conjugated hyperbilirubinemia, high frequency of Acute Flaccid Paralysis (AFP), liver cirrhosis, coagulation abnormalities hypoglycemia and fanconi syndrome as a result of kidney dysfunction (Annora G. et al). Often, symptoms include; vomiting, skin turns yellowish, jaundice, and diarrhea, slow rate of growth, regular nose bleeding and production of cabbage-like odor. When severe, it can affect the nervous system, cause liver cancer and kidney and liver failureCurrently, there are three known ways of treating tyrosinemia type I which are dietary treatment, seeking medication and lastly undertaking a liver transplant. People with tyrosinemia I have a specially prescribed diet that does not contain large amounts of tyrosine. For young children who are infected with the disease, they are fed with infant formula and natural foods. Furthermore, the health status, age and weight of the child should be carefully monitored to regulate and adjust the amount of diet that is provided.

Deficiency of Tyrosine aminotransferase which is encoded by TAT gene causes Type II tyrosinemia. This enzyme catalyzes the first reaction step in the catabolism of is also inherited in an autosomal recessive way. This disorder, at early childhood causes photophobia, excessive tearing, retarded mental development, affects the skin and eyes, causes redness pain in the eyes, painful skin lesions and lastly reduces intellectual development. This type of disease is controlled by reducing intake of high and phenylalanine and tyrosine containing foods.

Type III tyrosinemia is not so rampart in societies. It is caused by a hydroxyphenylpyruvate dioxygenase gene encoded hydroxyphenylpyruvate dioxygenase enzyme which aids the reaction of conversion of 4-hydroxyphenylpyruvate to homogentisic acid (Storey K., 2005). It is caused by exaggerated levels of tyrosine in the diet in newborns. This condition is characterized by seizures, intermittent ataxia and menta retardation. It is recommended to take large amounts of Vitamin C and low small amounts of phenylalanine containing foods.

Ornithine transcarbamylase deficiency (OTCD) is an inherited condition that is also passed to the offspring when both parents are infected. This is a urea cycle genetic disease that is caused by mutating the OTC enzyme. Ornithine transcarbamylase enzyme takes part in the urea cycle by converting carbamylase phosphate and orthinine to citrulline. Urea cycle is responsible for getting rid of the excess toxic ammonia generated by nitrogen produced from the deamination processes in the amino acid catabolism in form of urine in the liver leading to detoxification.When there is deficiency of this enzyme, there is accumulation of ammonia in the system damaging the nervous system damaging the liver by enhancing neurological defects. This disorder often becomes evident et the early stages of life. Infants suffering from this disorder have uncontrolled body temperatures, are lethargic, poor breathing rates and coma. There is also limited intellectual development, skin lesions, liver damage, and growth of brittle hair.


The disorder is prevented and treated dietary through eating of foods that are low in protein amounts to reduce excess production of ammonia in the body.


Maple syrup urine disease (MSUD) is also another autosomal recessive disorder that affects amino acids that are branched. It is also called branched chain ketoaciduria. The branched chain amino acids include leucine, valine and isoleucine.


This disorder is caused by a deficiency of branched chain alpha-keto acid dehydrogenase complex-BCKDC (Annora G. et al). This deficiency leads to accumulation of these three amino acids in blood. Further, an increased level of toxic metabolites of these amino acids is also observed in urine through the sweet odor that they produce as they produce sotolone compound. During birth, infants look normal but with time, they can suffer from severe damages of the brain if medication or treatment is not sought earlier enough. This condition shows dehydration, seizures, ketoacidosis, coma, lethargy and hypoglycemia. Maple syrup urine is genetically classified or it can be through the sequence of its signs and symptoms. It could be divided into intermediate MSUD, Classic severe MSUD, Thiamine responsive MSUD, Intermittent MSUD and E3-Deficient MSUD. Classic severe is the most wide spread and severe form known so far that manifests itself in a newborn at birth. Since this disease is caused by amino acids, to avoid it, people are advised to eat a diet that is less concentrated in proteins.

Argininosuccinic aciduria is also inherited condition that leads to production of high amounts of argininosuccinic acid in urine and blood. It develops from the citric acid cycle where Argininosuccinate lyase (ASL)enzyme is used to breakdown argininosuccinate to arginine, fumarate and dicarboxylic acid.Any mutation of this enzyme results into a reduced enzyme activity.


Argininosuccinate lyase is made of four monomers which are identical. For its catalysis, it has four active sites that help in the catalysis of argininosuccinate catabolism. Fumarate and arginine are formed from the breakdown of argininosuccinate using elimination method. This reaction step is the fourth one in a series of reaction in the urea cycle. At this stage fumarate enters the tricarboxylic acid cycle ( TCA) while arginine yields urea and orthinine. When this enzyme is mutated, it causes argininosuccinic aciduria which is also an autosomal recessive disorder which is not common.This leads to accumulation of compounds in the body which leads to hypothermia, vomiting, lethargy, muscle weakness, liver enlargement hyperventilation, mental retardation and hepatic fibrosis. The condition is managed through reduction of intake food with high protein contents.

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is an inherited autosomal disease which is as a result of amino acid catabolism. It actually prevents some fats from being converted to energy. This is mostly experienced during starvation and fasting. It is characterized by hypoglycemia or low blood sugar, lethargy or lack of energy and vomiting.
Like Post Reply
This is a great piece of biochemistry, can you give us more?
Like Post Reply

Possibly Related Threads…
Last Post

Users browsing this thread:
1 Guest(s)

Inborn Errors of Amino Acids Metabolism00