Adrenaline (Epinephrine)/Noradrenaline (Norepinephrine)
Acetylcholine
Acetylcholinesterase (EC 3.1.1.7, e.g. from Torpedo californica, TcAChE) hydrolysizes the neurotransmitter acetylcholine , producing group. ACh directly binds (via its nucleophilic Oγ atom) within the catalytic triad of (ACh/TcAChE structure 2ace). The residues are also important in the ligand recognition. After this binding acetylcholinesterase ACh.
Acetylcholine Receptors
Nicotinic Acetylcholine Receptors
Acetylcholinesterase
Dopamine
Dopamine Receptors
Agonists
- Amphetamine[1]
- Methamphetamine[2]
Antagonists
- Clebopride[3]
- Nafadotride[4]
- Eticlopride.
(3pbl).
.
Parkinson's disease
DOPA decarboxylase is responsible for the synthesis of dopamine and serotonin from L-DOPA and L-5-hydroxytryptophan, respectively. It is highly stereospecific, yet relatively nonspecific in terms of substrate, making it a somewhat uninteresting enzyme to study. Although it is not typically a rate-determining step of dopamine synthesis, the decarboxylation of L-DOPA to dopamine by DDC is the controlling step for individuals with Parkinson's disease[5], the second most common neurodegenerative disorder, occuring in 1% of the population over the age of 65. The loss of dopaminergic neurons is the main cause of cognitive impairment and tremors observed in patients with the disease. The hallmark of the disease is the formation of alpha-synuclein containing Lewy bodies.
Currently, treatment for the disease is aimed at DOPA decarboxylase inhibition. Since dopamine cannot cross the blood-brain barrier, it cannot be used to directly treat Parkinson's disease. Thus, exogenously administered L-DOPA is the primary treatment for patients suffering from this neurodegenerative disease. Unfortunately, DOPA decarboxylase rapidly converts L-DOPA to dopamine in the blood stream, with only a small percentage reaching the brain. By inhibiting the enzyme, greater amounts of exogenously administered L-DOPA can reach the brain, where it can then be converted to dopamine. [6]. Unfortunately, with continued L-Dopa treatment, up to 80% of patients experience 'wearing-off' symptoms, dyskinesias and other motor complications (referred to as the "on-off phenomenon". [7]. Clearly, a better understanding of the catalytic mechanism and enzymatic activity of DDC in both healthy and PD individuals is critical to drug design and treatment of the disease.
Serotonin
Serotonin receptors
