Editing Catecholamine (section)

===Biosynthesis===

Dopamine is the first catecholamine synthesized from DOPA. In turn, norepinephrine and epinephrine are derived from further metabolic modification of dopamine. The enzyme dopamine hydroxylase requires copper as a [[Cofactor (biochemistry)|cofactor]] (not shown in the diagram) and DOPA decarboxylase requires [[Pyridoxal phosphate|PLP]] (not shown in the diagram). The rate limiting step in catecholamine biosynthesis through the predominant metabolic pathway is the hydroxylation of <small>L</small>-tyrosine to <small>L</small>-DOPA.<ref>{{cite journal |url=https://link.springer.com/article/10.1007/s00702-014-1238-7 |doi=10.1007/s00702-014-1238-7 |title=Complex molecular regulation of tyrosine hydroxylase |date=2014 |last1=Tekin |first1=Izel |last2=Roskoski |first2=Robert |last3=Carkaci-Salli |first3=Nurgul |last4=Vrana |first4=Kent E. |journal=Journal of Neural Transmission |volume=121 |issue=12 |pages=1451–1481 |url-access=subscription }}</ref>

Catecholamine synthesis is inhibited by alpha-methyl-''p''-tyrosine ([[AMPT]]), which inhibits [[tyrosine hydroxylase]].{{Citation needed|date=February 2012}}

The amino acids [[phenylalanine]] and [[tyrosine]] are precursors for catecholamines. Both amino acids are found in high concentrations in [[blood plasma]] and the brain. In mammals, tyrosine can be formed from dietary phenylalanine by the enzyme [[phenylalanine hydroxylase]], found in large amounts in the liver. Insufficient amounts of phenylalanine hydroxylase result in [[phenylketonuria]], a metabolic disorder that leads to intellectual deficits unless treated by dietary manipulation.{{citation needed|date=April 2019}} Catecholamine synthesis is usually considered to begin with tyrosine. The enzyme [[tyrosine hydroxylase]] (TH) converts the amino acid <small>L</small>-tyrosine into 3,4-dihydroxyphenylalanine (<small>L</small>-DOPA). The hydroxylation of <small>L</small>-tyrosine by TH results in the formation of the DA precursor <small>L</small>-DOPA, which is metabolized by [[Aromatic L-amino acid decarboxylase|aromatic <small>L</small>-amino acid decarboxylase]] (AADC; see Cooper et al., 2002{{citation needed|date=April 2019}}) to the transmitter dopamine. This step occurs so rapidly that it is difficult to measure <small>L</small>-DOPA in the brain without first inhibiting AADC.{{citation needed|date=April 2019}} In [[neuron]]s that use DA as the transmitter, the decarboxylation of <small>L</small>-DOPA to dopamine is the final step in formation of the transmitter; however, in those neurons using [[norepinephrine]] (noradrenaline) or [[epinephrine]] (adrenaline) as transmitters, the enzyme [[Dopamine beta-hydroxylase|dopamine β-hydroxylase]] (DBH), which converts dopamine to yield norepinephrine, is also present. In still other neurons in which epinephrine is the transmitter, a third enzyme [[phenylethanolamine N-methyltransferase|phenylethanolamine ''N''-methyltransferase (PNMT)]] converts norepinephrine into epinephrine. Thus, a cell that uses epinephrine as its transmitter contains four enzymes (TH, AADC, DBH, and PNMT), whereas norepinephrine neurons contain only three enzymes (lacking PNMT) and dopamine cells only two (TH and AADC).{{citation needed|date=April 2019}}