Adrenaline (Epinephrine)/Noradrenaline (Norepinephrine)

• .
• .
• Phenylethanolamine N-methyltransferase (Noradrenaline N-Methyltransferase) catalyzes the conversion of norepinephrine (noradrenaline) to epinephrine (adrenaline). This is the last step in the conversion of tyrosine to adrenaline^[1].

Adrenergic receptors in general

Beta-adrenergic receptors

Beta-1 Adrenergic receptor

Article Beta-2 Adrenergic Receptor by Wayne Decatur, David Canner, Dotan Shaniv, Joel L. Sussman, Michal Harel

Article Beta-2 adrenergic receptor by Joel L. Sussman, Tala Curry, Michal Harel, Jaime Prilusky

Group:SMART:A Physical Model of the beta-Adrenergic Receptor

3D Structures of Adrenergic receptors

Beta-adrenergic receptor kinase

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

Nicotinic Acetylcholine Receptors in general

Binding site of AChR

Acetylcholine Receptor and its Reaction to Cobra Venom

Acetylcholinesterase

• Acetylcholinesterase: Treatment of Alzheimer's disease
  
• Torpedo californica acetylcholinesterase with bifunctional inhibitor
  
• Acetylcholinesterase: Substrate Traffic and Inhibition
  
• Acetylcholinesterase Inhibitor Pharmacokinetics
  
• Acetylcholinesterase inhibitors
  
• AChE inhibitors and substrates
  
• Human Acetylcholinesterase
  
• African Malaria Mosquito Acetylcholinesterase
  
• Acetylcholinesterase inhibited by nerve agent soman
  
• Acetylcholinesterase with DFP
  
• Acetylcholinesterase with OTMA
  
• Acetylcholinesterase with acetylcholine
  
• Acetylcholinesterase complexed with N-9-(1',2',3',4'-tetrahydroacridinyl)-1,8-diaminooctane
  
• Complex of TcAChE with an iminium galanthamine derivative
  
• Complex of TcAChE with bis-acting galanthamine derivative
  
• Cholinesterase
  
• Flexibility of aromatic residues in acetylcholinesterase
  
• Huperzine A Complexed with Acetylcholinesterase & Huperzine A Complexed with Acetylcholinesterase (Chinese)
  
• Acetylcholinesterase complexed with Tacrine, the 1st anti Alzheimer's drug
  
• Torpedo Californica Acetylcholinesterase in complex with an (R)-Tacrine-(10)-Hupyridone inhibitor
  
• Torpedo Californica Acetylcholinesterase in complex with an (S)-Tacrine-(10)-Hupyridone inhibitor
  
• Torpedo californica acetylcholinesterase with alkylene-linked tacrine dimer (5 carbon linker)
  
• Torpedo californica acetylcholinesterase with alkylene-linked tacrine dimer (7 carbon linker)
  
• Torpedo californica acetylcholinesterase with bifunctional inhibitor
  
• Tetramerization domain of acetylcholinesterase
  
• African Malaria Mosquito Acetylcholinesterase
• Group:SMART:Acetylcholinesterase:A Story of Substrate Traffic and Inhibition by Green Mamba Snake Toxin
  
• Treatments:AChE Inhibitor References
  

Alzheimer's Disease

Dopamine

DOPA decarboxylase

Dopamine Receptors

• Dopamine receptors 1 page
• Dopamine receptors 2 page

Agonists

• Amphetamine^[2]
• Methamphetamine^[3]

Antagonists

• Clebopride^[4]
• Nafadotride^[5]
• 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^[6], 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. ^[7]. 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". ^[8]. 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

Serotonin receptors, main page

3D structures of Serotonin receptors

5-HT3A receptor

Serotonin Transporter

See also Serotonin N-acetyltransferase