It is possible to relate Phenylketonuria to the four major strands of the grade twelve biology course because this rare disease affects all areas in the main functions of the body. PKU, is a rare inherited disorder that causes an amino acid called phenylalanine to build up in your body. It is caused by a defect in the gene that helps create the enzyme needed to break down phenylalanine. This affects the processes of metabolism by causing an error of PHE metabolism resulting from deficiency of PHE hydroxylase. It also deprives the body or is a complete absence in phenylalanine hydroxylase which is an enzyme involved in metabolizing or converting the amino acid phenylalanine into tyrosine, another amino acid.
It affects the subdivision of genetics at a molecular level because this disorder is inherited and is autosomal recessive. Two copies of the gene is altered which means a mutation occurred. PKU also has a history of causing intellectual disability, seizures, delayed development, behavior problems, and psychiatric disorders which disallows proper function of homeostasis. PKU has affected many people as studies show it has affected many populations such as Western Europe to Germany. Metabolic ProcessesMutations in the phenylalanine hydroxylase (PAH) gene is a hereditary error of metabolism. When these mutations occur the catalytic activity begins to affect the the pathway that breaks down the enzyme phenylalanine (PHE).
A contributor to the disease called tetrahydrobiopterin (BH4) converts PHE to tyrosine (TYR). PAH enzyme relates to the liver and requires BH4 for this conversion to happen. Due to the deficiency in PAH and the contributor to the disease BH4, the result ends up being an accumulation of excess phenylalanine. This accumulation is a negative product of toxic effects that can cause a intellectual disability that is irreversible and severe if it goes untreated. Other disabilities that associated with PKU if it is untreated include autistic behaviour, problematic motor movement, eczematous rash, seizures,behavioural impairment and psychiatric disturbances are more common with age (Naz Al Hafid and John Christodoulou, 2015).
PHE is mostly found in the blood stream and in urine of metabolites because of the a chemical reaction that transfers an amino group to a ketoaid to form new amino acids of PHE to phenylpyruvate (Marte I. Flydal and Aurora Martinez, 2013).Molecular GeneticsThis disease is autosomal recessive meaning two copies of an abnormal gene must be present in order for the disease to develop. This means both parents of the individual with the disorder carries the altered or abnormal gene. This all starts with the PHE gene being altered (mutated). This results in an inactivating mutation in the gene coding for the phenylalanine hydroxylase enzyme and this is the reason why individuals with this disorder are unable to convert PHE into TYR resulting in a buildup of protein. During translation ribosomal subunits attach on the strand of mRNA where they attract tRNA molecules chained to amino acids.
A long chain of amino acids arrives and the ribosome decodes the mRNA sequence into a polypeptide, or a new protein.HomeostasisPKU has a lot of negative effects on the body such as intellectual disability, seizures, delayed development, behavior problems, and psychiatric disorders. PAH, has the job of changing some of the PHE you eat into a different amino acid called tyrosine.
TYR is used to make a brain neurotransmitter chemical called dopamine. Evidence suggests that changes in PAH function in PKU can cause lower amounts of dopamine in the brain causing conditions like schizophrenia and neurodegenerative diseases. If there is a great amount of dopamine missing the chances are that it is causing great impairment to the mental performance and can be very problematic (Mental Health Blog, 2015). It is understood that an individual with PKU has a build up of phenylalanine in the body but this build up can be very harmful to the central nervous system and cause brain damage. This disorder often results in epilepsy episodes if food are eaten with a large amount of PHE and a low protein diet was not implemented at birth.
The functions of the body by which PHE affects the brain are poorly understood. Hyperphenylalaninemia is a medical condition that is derived from PKU but a much stronger form of it where it has extreme levels of PHE in the blood. A brief decrease in PHE levels within hyperphenylalaninemic matter may be a reason or the condition for a PKU-related seizure to occur. A low in protein diet certainly prevents being susceptible to seizures (Martynyuk AE1, Ucar DA, Yang DD, Norman WM, Carney PR, Dennis DM, Laipis PJ, 2007).Population DynamicsPKU seems to be a known disease in a decent spread across the map. Approximately 1 per 10,000 newborns in the most of the Caucasian populations of northern and western Europe have been affected by the protein buildup disorder.
The number has also increased in Germany with 2,500 people being diagnosed with PKU affecting children, adolescents and adults. The number of people who have been affected and the certain areas are most definitely distributed in clumps. The spectrum of mutations in patients with PKU living in Germany is total of 546 independent alleles that were all investigated.
The mutations were classified to be for 535 PKU alleles (98%) and it turned out to be that there was 91 different mutations (J. Zschocke and Georg F. Hoffmann, 1999).