Editing Dopamine (section)

===Synthesis===
Dopamine is [[biosynthesis|synthesized]] in a restricted set of cell types, mainly neurons and cells in the [[adrenal medulla|medulla]] of the [[adrenal gland]]s.<ref name=Seeman/> The primary and minor [[metabolic pathway]]s respectively are:

:Primary: <small>L</small>-Phenylalanine → <small>L</small>-Tyrosine → <small>L</small>-DOPA → Dopamine<ref name="Trace amine template 1" /><ref name="Trace amine template 2" />
:Minor: <small>L</small>-Phenylalanine → <small>L</small>-Tyrosine → ''p''-Tyramine → Dopamine<ref name="Trace amine template 1" /><ref name="Trace amine template 2" /><ref name="CYP2D6 tyramine-dopamine metabolism" />
:Minor: <small>L</small>-Phenylalanine → [[L-m-tyrosine|''m''-Tyrosine]] → [[meta-tyramine|''m''-Tyramine]]  → Dopamine<ref name="CYP2D6 tyramine-dopamine metabolism" /><ref name="Tyrosine 3-hydroxylase m-tyrosine synthesis">{{cite encyclopedia|title=EC 1.14.16.2&nbsp;– Tyrosine 3-monooxygenase (Homo sapiens)|url=http://www.brenda-enzymes.org/enzyme.php?ecno=1.14.16.2&Suchword=&reference=&organism%5B%5D=Homo+sapiens&show_tm=0| encyclopedia =BRENDA|publisher=Technische Universität Braunschweig|access-date=7 October 2016|date=July 2016|quote = Substrate: L-phenylalanine + tetrahydrobiopterin + O2<br />Product: L-tyrosine + 3-hydroxyphenylalanine [(aka m-tyrosine)] + dihydropteridine + H2O<br />Organism: Homo sapiens}}<br />[http://www.brenda-enzymes.org/structure.php?show=reaction&id=428743&type=S&displayType=marvin Reaction diagram]</ref><ref name="AADC m-tyramine synthesis">{{cite encyclopedia|title=EC 4.1.1.28&nbsp;– Aromatic-L-amino-acid decarboxylase (Homo sapiens)|url=http://www.brenda-enzymes.org/enzyme.php?ecno=4.1.1.28&Suchword=&reference=&organism%5B%5D=Homo+sapiens&show_tm=0| encyclopedia =BRENDA|publisher=Technische Universität Braunschweig|access-date=7 October 2016|date=July 2016|quote = Substrate: m-tyrosine<br />Product: m-tyramine + CO2<br />Organism: Homo sapiens}}<br />[http://www.brenda-enzymes.org/structure.php?show=reaction&id=407269&type=S&displayType=marvin Reaction diagram]</ref>

The direct precursor of dopamine, [[L-DOPA|<small>L</small>-DOPA]], can be synthesized indirectly from the [[essential amino acid]] [[phenylalanine]] or directly from the non-essential amino acid [[tyrosine]].<ref name=Musacchio/> These [[amino acid]]s are found in nearly every protein and so are readily available in food, with tyrosine being the most common. Although dopamine is also found in many types of food, it is incapable of crossing the [[blood–brain barrier]] that surrounds and protects the brain.<ref name="Nice-pharma"/> It must therefore be synthesized inside the brain to perform its [[neurotransmission|neuronal activity]].<ref name="Nice-pharma"/>

<small>L</small>-Phenylalanine is converted into <small>L</small>-tyrosine by the [[enzyme]] [[phenylalanine hydroxylase]], with [[allotropes of oxygen#Dioxygen|molecular oxygen]] (O<sub>2</sub>) and [[tetrahydrobiopterin]] as [[cofactor (biochemistry)|cofactors]]. <small>L</small>-Tyrosine is converted into <small>L</small>-DOPA by the enzyme [[tyrosine hydroxylase]], with tetrahydrobiopterin, O<sub>2</sub>, and iron (Fe<sup>2+</sup>) as cofactors.<ref name=Musacchio>{{cite book |title=Biochemistry of Biogenic Amines |chapter=Chapter 1: Enzymes involved in the biosynthesis and degradation of catecholamines | vauthors= Musacchio JM | veditors = Iverson L |publisher=Springer | isbn = 978-1-4684-3171-1 |year=2013 |pages=1–35}}</ref> <small>L</small>-DOPA is converted into dopamine by the enzyme [[aromatic L-amino acid decarboxylase|aromatic <small>L</small>-amino acid decarboxylase]] (also known as DOPA decarboxylase), with [[pyridoxal phosphate]] as the cofactor.<ref name=Musacchio/>

Dopamine itself is used as precursor in the synthesis of the neurotransmitters norepinephrine and epinephrine.<ref name=Musacchio/> Dopamine is converted into norepinephrine by the enzyme [[dopamine beta hydroxylase|dopamine β-hydroxylase]], with O<sub>2</sub> and [[ascorbic acid|<small>L</small>-ascorbic acid]] as cofactors.<ref name=Musacchio/> Norepinephrine is converted into epinephrine by the enzyme [[phenylethanolamine N-methyltransferase|phenylethanolamine ''N''-methyltransferase]] with [[S-Adenosyl methionine|''S''-adenosyl-<small>L</small>-methionine]] as the cofactor.<ref name=Musacchio/>

Some of the cofactors also require their own synthesis.<ref name=Musacchio/> Deficiency in any required amino acid or cofactor can impair the synthesis of dopamine, norepinephrine, and epinephrine.<ref name=Musacchio/>