The UPB1 gene provides instructions for making an enzyme called beta-ureidopropionase. This enzyme is involved in the breakdown of molecules called pyrimidines, which are building blocks of DNA and its chemical cousin RNA.
The beta-ureidopropionase enzyme is involved in the last step of the process that breaks down pyrimidines. This step converts N-carbamyl-beta-aminoisobutyric acid to beta-aminoisobutyric acid and also breaks down N-carbamyl-beta-alanine to beta-alanine, ammonia, and carbon dioxide. Both beta-aminoisobutyric acid and beta-alanine are thought to play roles in the nervous system. Beta-aminoisobutyric acid increases the production of a protein called leptin, which has been found to help protect brain cells from damage caused by toxins, inflammation, and other factors. Research suggests that beta-alanine is involved in sending signals between nerve cells (synaptic transmission) and in controlling the level of a chemical messenger (neurotransmitter) called dopamine.
At least 16 UPB1 gene mutations have been identified in people with beta-ureidopropionase deficiency. This disorder causes excessive amounts of N-carbamyl-beta-aminoisobutyric acid and N-carbamyl-beta-alanine to be released in the urine. Affected individuals may also have a variety of neurological problems such as seizures and intellectual disability, ranging from mild to severe. Some people with beta-ureidopropionase deficiency have no neurological symptoms, and the disorder can only be diagnosed with laboratory testing.
The mutations that cause beta-ureidopropionase deficiency reduce or eliminate beta-ureidopropionase enzyme activity. Loss of this enzyme function reduces the production of beta-aminoisobutyric acid and beta-alanine, and leads to an excess of their precursor molecules, N-carbamyl-beta-aminoisobutyric acid and N-carbamyl-beta-alanine, which are released in the urine. Reduced production of beta-aminoisobutyric acid and beta-alanine may impair their functions in the nervous system, leading to neurological problems in some people with beta-ureidopropionase deficiency. The extent of the reduction in enzyme activity caused by a particular UPB1 gene mutation, along with other genetic and environmental factors, may determine whether people with beta-ureidopropionase deficiency develop neurological problems and the severity of these problems.
- beta-alanine synthase
- n-carbamoyl-beta-alanine amidohydrolase
- ureidopropionase, beta