Structural Biochemistry/MAO B enzyme

MAO B is an enzyme called monoamine oxidase B. It helps in recycling neurotransmitters, communication molecules, in the brain. Both MAO B and MAO A, its cousin, removes molecular pieces from neurotransmitters. This is a part of a process that inactivates the neurotransmitters. Blocking the actions of MAO enzymes has been discovered by scientists. This is beneficial because it helps in the preservation of the levels of neurotransmitters. This helps people with disorders such as depression and Parkinson's disease.

Side Effects

MAO inhibitors have many side effects that are undesirable. Some mild effects include increased heart rate, tremors, and sexual function problems. Some side effects that are more serious include large dips in blood pressure, seizures, and difficulty breathing. People who are taking MAO inhibitors should be cautious in the food that they eat. They can not eat food that contains tyramine. Tyramine can be found in dried fruits, cheese, wine, and many others. The side effects for this drug occurs mainly because drugs do not attach to MAO enzymes perfectly for both MAO B or MAO A.

Structure

Edmondson et al. states that the structural features of the human enzyme has a hydrophic bipartite elongated cavity that holds a total volume that is approximately 700 Å3. hMAO-A has a single cavity that displays more of a round shape and is comparatively larger in volume than the substrate cavity of hMAO-B. The first cavity of hMAO-B is called the entrace cavity of about 290 Å3, and the second substrate cavity or active site cavity that is between both anisoleucine199 side chain of about 390 Å3 acts as a gate. It can either exist as an open or a closed form depending on the substrate or bound inhibitor. This has been shown to play an important role in defining the inhibitor specificity of hMAO B. Then there is the FAD coenzyme at the end of the substrate cavity with sites that favor amine binding regarding the flavin consisting of two nearly parallel tyrosyl (398 and 435) remains that form an aromatic cage.

Differences between MAOA and MAOB

MAO-A plays an important role in the metabolism of tyramine. Some particular irreversible inhibition of MAO-A can lead to a dangerous pressor effect when consumed foods are high in tyramine such as cheese. MAO-A also plays an important role in the metabolism of serotonin, noradrenaline, and dopamine. MAO-B, an enzyme on the outer mitochondrial membrane, metabolizes dopamine neurotransmitter and catalyzes the oxidation of arylalkylamineneurotransmitters. Generally, MAOA, mMonoamine Oxidase A, metabolize norepinephrine, serotonin, Dopamine, and other less clinically relevant chemicals. In contrast, Monoamine Oxidase B, MAO-B, metabolizes Dopamine and other less clinically relevant chemicals. The differences between the substrate selectivity of the two enzymes play a significant role when treating specific disorders. For example, Monoamine Oxidase A inhibitors have been involved in the treatment of depression while Monoamine Oxidase B inhibitors have been involved in the treatment of Parkinson's Disease.

References

• Edmondson, Dale E.; Binda, Claudia; Mattevi, Andrea (2007). "Structural insights into the mechanism of amine oxidation by monoamine oxidases a and B". Archives of Biochemistry and Biophysics. 464 (2): 269–76. doi:10.1016/j.abb.2007.05.006. PMC 1993809. PMID 17573034.
• Binda, Claudia; Hubálek, Frantisek; Li, Min; Herzig, Yaacov; Sterling, Jeffrey; Edmondson, Dale E.; Mattevi, Andrea (2004). "Crystal Structures of Monoamine Oxidase B in Complex with Four Inhibitors of theN-Propargylaminoindan Class". Journal of Medicinal Chemistry. 47 (7): 1767–74. doi:10.1021/jm031087c. PMID 15027868.