Inborn Metabolic Disease: Tyrosinemia
Metabolism is the different processes and enzyme-catalyzed reactions that the body uses to make energy. 1 Proteins, carbohydrates, fats, and amino acids are used to make the sugars and acids needed to fuel the body with the necessary components to sustain life. 1 The body can then store this energy in tissues, mainly in the liver and muscles, or it can store the energy in the form of body fat. This body fat can then act as a reserve or it can be used directly when it is needed.
Metabolic disorders take place when atypical chemical reactions take place and prevent the vital processes from producing the normal needed products. 2 They can also present themselves in the form of preventing the body from controlling a normal level of a certain chemical, which in turn can take a large toll on a person’s liver, muscles, and heart. 2 The metabolic disorder that will be reviewed in this paper is tyrosinemia. Tyrosinemia is a metabolic disorder regarded as an increase in the levels of the amino acid, tyrosine, in the blood. 3 This is due to a deficiency of a specific enzyme that is part of the multi-step process of tyrosine degradation. This leads to a buildup of the amino acid which in result wreaks havoc on the body’s organs. 3 There are three main types of tyrosinemia: Type I tyrosinemia, Type II tyrosinemia, and Type III tyrosinemia3. Each type is different in its symptoms, severity, and in the enzyme that is defective.
The amino acid that is involved in this disorder is tyrosine. Tyrosine is one of the most insoluble amino acids4. It comes from two sources, diet and hydroxylation of phenylalanine. 4 The degradation of tyrosine is a catabolic pathway. Catabolic pathways are used to break down larger molecules into small units that are then used for energy formation. 4 Tyrosine is both glucogenic and ketogenic because at the end of its degradation it forms both fumarate (glucogenic) and acetoacetate (ketogenic).5 Tyrosine’s degradation glucogenic product, fumarate, is a four carbon intermediate of the citric acid cycle, which is a precursor for gluconeogenesis.5 When glucose levels are low, glucogenic amino acids become the major carbon source for gluconeogenesis.5 They can also be used for energy storage by being converted to glycogen or fatty acids. Tyrosine’s degradation ketogenic product, acetoacetate, can be converted into acetyl CoA; however this does not yield any net production of oxaloacetate.5 Therefore it cannot be used in the gluconeogenesis pathway when glucose levels are low. If glucose is available and the production of oxaloacetate is normal, then acetyl CoA condenses with oxaloacetate, and can be catabolized for energy in the citric acid cycle or converted to fatty acids.5
Symptoms & Diagnosis
Type I Symptoms:
The most severe type of tyrosinemia is Type I. It also comes with two different diagnosis of either acute or chronic.6 The symptoms also vary from person to person. The acute form is usually...