Synthesis of Neurotransmitter Substances

A major feature of neurotransmitter synthesis is the observation that the neurotransmitters themselves are all nitrogenous substances and in most cases are ultimately derived from dietary protein (Fig. 3). A singular exception to this concept is acetylcholine. Choline can be derived Irom serine, although a significant portion is derived from dietary lecithin. While dietary protein is not directly converted into neurotransmitters, the amino acids that are derived from these proteins can be used unchanged (glycine, glutamate, or aspartatic acid), metabolized to specific derivatives (catecholamines, etc.), 

Giycine Giutsmste Aspsrtste -Amino Butyric scid 

Tyrosine hydroxylase is an iron-containing mixed function oxidase that utilizes tetrahydrobiopterin, oxygen, and L-tyrosine as cosubstrates. Molecular oxygen is transferred from O2 to the aromatic ring of tyrosine. In recent years the molecular properties and the mechanisms that regulate the activity of this enzyme have been studied in depth by several laboratories (Kuhn and Lovenberg, 1983). 

In brief, it has long been known that the activity of this enzyme is powerfully inhibited by catecholamine end products (dopamine, norepinephrine, and epinephrine). This inhibition is expressed as a competition of the catecholamine with tetrahydrobiopterin. During the past decade, however, ideas on this regulation have been further refined. 

Tyrosine hydroxylase is a substrate for protein kinases (see following section on second messengers), and once phosphorylated, the enzyme is less sensitive to end-product inhibition and thereby appears to have a greater affinity for hydroxylase cofactor. One study suggests that under physiologic 

---

In some mammalian cells, enzymes comprising partial spans of biosynthetic pathways are inside and some outside the mitochondrial matrix space. Therefore, in the liver, six mitochondrial membrane transport proteins are required for urea synthesis, three for gluconeogenesis [7,8], and three others participate in ammonia-genesis [9] in the kidney. The synthesis of neurotransmitter substances such as acetylcholine, glutamate and y-amino butyric acid requires the participation of metabolite transporters in mitochondrial membranes of nervous tissue [9,10]. 

---