Tyrosine aminotransferase

3DYD6898234724ENSG00000198650ENSMUSG00000001670P17735Q8QZR1NM_000353NM_146214NP_000344NP_666326Tyrosine aminotransferase (or tyrosine transaminase) is an enzyme present in the liver and catalyzes the conversion of tyrosine to 4-hydroxyphenylpyruvate.(See Template:Leucine metabolism in humans – this diagram does not include the pathway for β-leucine synthesis via leucine 2,3-aminomutase) Tyrosine aminotransferase (or tyrosine transaminase) is an enzyme present in the liver and catalyzes the conversion of tyrosine to 4-hydroxyphenylpyruvate. In humans, the tyrosine aminotransferase protein is encoded by the TAT gene. A deficiency of the enzyme in humans can result in what is known as type II tyrosinemia, wherein there is an abundance of tyrosine as a result of tyrosine failing to undergo an aminotransferase reaction to form 4-hydroxyphenylpyruvate. Structures of the three main molecules involved in chemical reaction catalyzed by the tyrosine aminotransferase enzyme are shown below: the amino acid tyrosine, the prosthetic group pyridoxal phosphate, and the resulting product 4-hydroxyphenylpyruvate. Each side of the dimer protein includes pyridoxal phosphate (PLP) bonded to the Lys280 residue of the tyrosine aminotransferase molecule. The amine group of tyrosine attacks the alpha carbon of the imine bonded to Lys280, forming a tetrahedral complex and then kicking off the LYS-ENZ. This process is known as transimination by the act of switching out the imine group bonded to PLP. The newly formed PLP-TYR molecule is then attacked by a base. A possible candidate for the base in the mechanism could be Lys280 that was just pushed off of PLP, which sequesters the newly formed amino group of the PLP-TYR molecule. In a similar mechanism of aspartate transaminase, the lysine that forms the initial imine to PLP later acts as the base that attacks the tyrosine in transimination. The electrons left behind from the loss of the proton move down to form a new double bond to the imine, which in turn pushes the already double bonded electrons through PLP and end up as a lone pair on the positively charged nitrogen in the six-membered ring of the molecule. Water attacks the alpha carbon of the imine of PLP-TYR and through acyl substitution kicks off the nitrogen of PLP and forming pyridoxamine phosphate (PMP) and 4-hydroxyphenylpyruvate.