How DOPA Decarboxylase Affects Neurotransmitter Synthesis

Thu, 05/12/2016 - 11:01

DOPA decarboxylase (DDC) is responsible for catalyzing the conversion of aromatic amino acids into their corresponding amines during the synthesis of several important neurotransmitters. Specifically, DDC catalyzes the decarboxylation of L-DOPA to dopamine, L5-HTP to serotonin, L-histidine to histamine, phenylalanine to phenethylamine, L-tyrosine to tyramine, and tryptophan to tryptamine.

A number of mutations in the DDC gene can cause aromatic L-amino-acid decarboxylase deficiency (AADCD) (Gücüyener et al., 2014). AADCD is an inborn error in neurotransmitter metabolism that leads to combined serotonin and catecholamine deficiency. DDC's critical role in neurotransmitter synthesis makes it an important target in the study of Parkinson's disease, depression and other neuroscience related diseases.

Parkinson's patients experience motor system symptoms due to reduced levels of dopamine in the substantia nigra portion of the brain. The conversion of L-DOPA to dopamine by DDC is not typically a rate-limiting step of dopamine synthesis in healthy individuals, however it is a determining factor for patients with Parkinson's disease.

Although dopamine cannot cross the blood-brain barrier, treatment with exogenous L-DOPA can temporarily alleviate some symptoms as it is broken down by DDC in the brain. Unfortunately, up to 95% of the administered L-DOPA is metabolized by DDC in the blood prior to crossing the blood-brain barrier, causing adverse side effects including nausea, dyskinesias, and joint stiffness. However DDC inhibitors can be used to prevent premature L-DOPA metabolism in the blood, and thereby both increase efficacy and reduce side effects (Burkhard et al., 2001).

DCC antibody DCC antibody

IHC analysis using DDC Antibody [NBP1-56918] on renal corpuscle cells in human kidney tissue

WB analysis of DDC Antibody [NB300-174] on rat adrenal medulla

Novus Biologicals offers a wide range of DDC research reagents for use in neuroscience research. For example, researchers used Novus' Dopa Decarboxylase/DDC Antibody (NB300-174) to show that neuronal and extraneuronal DCC was present at early developmental stages in the brain stem and the basal ganglia (Blechingberg et al., 2010). In another study Novus' Dopa Decarboxylase/DDC Antibody (NBP1-56918) was used to demonstrate that DCC and VMAT2, which is necessary for packaging dopamine, were present in neurons within the A11 dopaminergic cell group (Koblinger et al., 2014). Finally, researchers used Novus' DOPA Decarboxylase Antibody (NB100-1785) in a study on attention-deficit hyperactivity disorder (Voeller 2004).

Gücüyener K, Kasapkara CS, Tümer L, Verbeek MM. Aromatic L-Amino acid decarboxylase deficiency: A new case from Turkey with a novel mutation. Ann Indian Acad Neurol. 2014 Apr;17(2):234-6. [PMID: 25024584]

Burkhard P, Dominici P, Borri-Voltattorni C, Jansonius JN, Malashkevich VN. Structural insight into Parkinson's disease treatment from drug-inhibited DOPA decarboxylase. Nat Struct Biol. 2001 Nov;8(11):963-7. [PMID: 11685243]

Blechingberg J, Holm IE, Johansen MG et al. Aromatic l-amino acid decarboxylase expression profiling and isoform detection in the developing porcine brain. Brain Res 2010 Jan 13 [PMID: 19857468]

Koblinger Kathrin, Fuzesi Tamas, Ejdrygiewicz Jillian et al. Characterization of A11 neurons projecting to the spinal cord of mice. PLoS One. 2014 Oct 24 [PMID: 25343491]

Voeller KK. Attention-deficit hyperactivity disorder (ADHD). J Child Neurol. 2004 Oct;19(10):798-814. [PMID: 15559895]

Blog Topics