It has been called “the epitome of human biochemical genetics”. PKU (OMIM #261600) is one of the earliest defined inborn errors of metabolism, and has a well-described history. SUAC, succinylacetone BH4, tetrahydrobiopterin HPA, hyperphenylalaninemia, PKU, phenylketonuria TYR, tyrosinemia. Green line represents mitochondrial membrane. Enzyme deficiencies are shown in the red star shapes. Overview of phenylalanine and tyrosine metabolism. This review will further discuss common inborn errors of amino acid metabolism, their clinical presentation, diagnostic evaluation, treatment and management approaches. Through developments in the study of PKU, the concept of dietary restriction of the offending amino acid as a treatment strategy led to subsequent evolution of the field of “Metabolic Nutrition” ( 5). Subsequently, the identification of a defect in phenylalanine metabolism, phenylketonuria (PKU) led to evolution of Newborn Screening (NBS) and its success as discussed in another topic ‘ Newborn screening and the changing face of inborn errors of metabolism in the United States’ of this issue. Thus was born a new field of medicine “Inborn Errors of Metabolism” (IEM) and the one-gene-one enzyme concept ( 3, 4). Sir Archibald Garrod investigated why the urine of some individuals turned black, working out the defect in tyrosine metabolism at homogentisic acid oxidase. Most of the non-essential amino acids such as alanine, arginine, asparagine, aspartate, glutamate, glutamine, glycine, proline and serine, are synthesized from glucose while tyrosine is synthesized from the metabolism of phenylalanine, and cysteine from the metabolism of methionine ( 2).Īlkaptonuria, an inborn error of amino acid metabolism, has the distinction of being the first metabolic disorder described. Nine amino acids (histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine) are considered as “essential”, i.e., essential in the diet as humans are unable to synthesize them endogenously. Humans utilize 21 different amino acids with the 21 st amino acid-selenocysteine, being unique that it does not follow the canonical pathways of the other 20 proteinogenic amino acids synthesis, but has an important role in various cellular processes such as oxidative stress, signaling pathways, thyroid hormone metabolism, protein folding, and selenium homeostasis ( 1). When needed, the carbon skeletons can be used to produce glucose or its derivatives (such as glycogen or fatty acids) to support plasma glucose levels or provide energy during fasting.ĭietary proteins are key sources of essential amino acids in mammals and humans, while non-essential amino acids can by synthesized endogenously. Proteins not only serve as structural or working compounds, they can also be metabolized to create energy. In healthy individuals consuming a regular diet, only a small amount of protein intake is wasted in urine or feces. ![]() Amino acids are used efficiently by the body by multiple mechanisms such as recycling, transamination, or energy production. ![]() They also form the backbones of critical nitrogen-based compounds such as cytochromes, heme, hormones, melanin, neurotransmitters, nucleotides/nucleic acids and others. This review will discuss the more common disorders caused by inborn errors in amino acid metabolism.Īmino acids are the building blocks of proteins, including structural proteins and enzymes. ![]() Amino acid disorders also led to the evolution of the field of metabolic nutrition and offending amino acid restricted formula and foods. The key concept of a single gene defect leading to a single enzyme dysfunction, leading to “intoxication” with a precursor in the metabolic pathway was vital to linking genetics and metabolic disorders and developing screening and treatment approaches as described in other chapters in this issue. A metabolic defect in the metabolism of tyrosine (homogentisic acid oxidase deficiency) historically defined Archibald Garrod as key architect in linking biochemistry, genetics and medicine and creation of the term ‘Inborn Error of Metabolism’ (IEM). In addition to their role as building blocks of protein, amino acids are key energy source (ketogenic, glucogenic or both), are building blocks of Kreb’s (aka TCA) cycle intermediates and other metabolites, and recycled as needed. Human utilize 21 different amino acids most of these can be synthesized endogenously, but 9 are “essential” in that they must be ingested in the diet. Each amino acid has an amino group, a carboxylic acid, and a unique carbon structure. Amino acids serve as key building blocks and as an energy source for cell repair, survival, regeneration and growth.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |