SUMMARY / RELATED TOPICS

Acetylcholinesterase

Acetylcholinesterase known as AChE or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme that catalyzes the breakdown of acetylcholine and of some other choline esters that function as neurotransmitters. AChE is found at neuromuscular junctions and in chemical synapses of the cholinergic type, where its activity serves to terminate synaptic transmission, it belongs to carboxylesterase family of enzymes. It is the primary target of inhibition by organophosphorus compounds such as nerve agents and pesticides. AChE is a hydrolase, it has a high catalytic activity—each molecule of AChE degrades about 25,000 molecules of acetylcholine per second, approaching the limit allowed by diffusion of the substrate. The active site of AChE comprises 2 subsites -- the esteratic subsite; the structure and mechanism of action of AChE have been elucidated from the crystal structure of the enzyme. The anionic subsite accommodates the positive quaternary amine of acetylcholine as well as other cationic substrates and inhibitors.

The cationic substrates are not bound by a negatively charged amino acid in the anionic site, but by interaction of 14 aromatic residues that line the gorge leading to the active site. All 14 amino acids in the aromatic gorge are conserved across different species. Among the aromatic amino acids, tryptophan 84 is critical and its substitution with alanine results in a 3000-fold decrease in reactivity; the gorge penetrates halfway through the enzyme and is 20 angstroms long. The active site is located 4 angstroms from the bottom of the molecule; the esteratic subsite, where acetylcholine is hydrolyzed to acetate and choline, contains the catalytic triad of three amino acids: serine 200, histidine 440 and glutamate 327. These three amino acids are similar to the triad in other serine proteases except that the glutamate is the third member rather than aspartate. Moreover, the triad is of opposite chirality to that of other proteases; the hydrolysis reaction of the carboxyl ester leads to the formation of an acyl-enzyme and free choline.

The acyl-enzyme undergoes nucleophilic attack by a water molecule, assisted by the histidine 440 group, liberating acetic acid and regenerating the free enzyme. During neurotransmission, ACh is released from the presynaptic neuron into the synaptic cleft and binds to ACh receptors on the post-synaptic membrane, relaying the signal from the nerve. AChE located on the post-synaptic membrane, terminates the signal transmission by hydrolyzing ACh; the liberated choline is taken up again by the pre-synaptic neuron and ACh is synthesized by combining with acetyl-CoA through the action of choline acetyltransferase. A cholinomimetic drug disrupts this process by acting as a cholinergic neurotransmitter, impervious to acetylcholinesterase's lysing action. For a cholinergic neuron to receive another impulse, ACh must be released from the ACh receptor; this occurs only when the concentration of ACh in the synaptic cleft is low. Inhibition of AChE leads to accumulation of ACh in the synaptic cleft and results in impeded neurotransmission.

Irreversible inhibitors of AChE may lead to muscular paralysis, bronchial constriction, death by asphyxiation. Organophosphates, esters of phosphoric acid, are a class of irreversible AChE inhibitors. Cleavage of OP by AChE leaves a phosphoryl group in the esteratic site, slow to be hydrolyzed and can become covalently bound. Irreversible AChE inhibitors have been used in insecticides and nerve gases for chemical warfare. Carbamates, esters of N-methyl carbamic acid, are AChE inhibitors that hydrolyze in hours and have been used for medical purposes. Reversible inhibitors occupy the esteratic site for short periods of time and are used to treat of a range of central nervous system diseases. Tetrahydroaminoacridine and donepezil are FDA-approved to improve cognitive function in Alzheimer's disease. Rivastigmine is used to treat Alzheimer's and Lewy body dementia, pyridostigmine bromide is used to treat myasthenia gravis. An endogenous inhibitor of AChE in neurons is Mir-132 microRNA, which may limit inflammation in the brain by silencing the expression of this protein and allowing ACh to act in an anti-inflammatory capacity.

It has been shown that the main active ingredient in cannabis, tetrahydrocannabinol, is a competitive inhibitor of acetylcholinesterase. AChE is found in many types of conducting tissue: nerve and muscle and peripheral tissues and sensory fibers, cholinergic and noncholinergic fibers; the activity of AChE is higher in motor neurons than in sensory neurons. Acetylcholinesterase is found on the red blood cell membranes, where different forms constitute the Yt blood group antigens. Acetylcholinesterase exists in multiple molecular forms, which possess similar catalytic properties, but differ in their oligomeric assembly and mode of attachment to the cell surface. In mammals, acetylcholinesterase is encoded by a single AChE gene while some invertebrates have multiple acetylcholinesterase genes. Note higher vertebrates encode a related paralog BCHE with 50% amino acid identity to ACHE. Diversity in the transcribed products from the sole mammalian gene arises from alternative mRNA splicing and post-translational associations of catalytic and structural subunits.

There are three known forms: T, R, H. The major form of acetylcholinesterase found in brain and other tissues, known as is the hydrophilic species, which forms disulfide-linked oligomers with coll

Jane I. Guyer

Jane I. Guyer is the George Armstrong Kelly Professor in the Department of Anthropology at The Johns Hopkins University. Before coming to Hopkins, Guyer taught at Northwestern University, Harvard University, Boston University, she has published extensively on economic development in West Africa, on the productive economy, the division of labor, the management of money. She was elected to the National Academy of Sciences in 2008 and serves on several international and national committees, including the International Advisory Group to the World Bank and the governments of Chad and Cameroon on the Chad–Cameroon Petroleum Development and Pipeline Project, the Lost Crops of Africa panel published by the National Academy, the Board and Executive Committee of the African Studies Association, her research has been celebrated for her contributions not just to empirical research but theoretical discourse on several topics. Guyer was born in Scotland and attended the London School of Economics, earning a bachelor's degree in sociology in 1965.

She attended the University of Rochester, where the department focused on the British social anthropological tradition, studied under Robert Merrill and Alfred Harris. She completed her graduate training in 1972, her dissertation was titled The Organizational Plan of Traditional Farming: Western Nigeria. Guyer earned her first teaching position at the University of North Carolina before she had completed her studies. Family and Farm in Southern Cameroon, 1984. Boston University, African Studies Center. Research Study #15. Feeding African Cities: Essays in Regional Social History, 1987. Edinburgh University Press and the International African Institute. An African Niche Economy, 1997. Edinburgh University Press and the International African Institute. Time and African Land Use: Ethnography and Remote Sensing. 2007. Guyer and Eric Lambin Special issue of Human Ecology, vol. 35, no. 1. Money Matters: Instability and Social Payments in the Modern History of West African Communities, 1995. Heinemann. Money Struggles and City Life, 2002.

Heinemann. Marginal Gains: Monetary Transactions in Atlantic Africa, 2004. University of Chicago Press. Cultures of Monetarism. Collected papers and abstracts To Dance the Spirit: Masks of Liberia, 1986. Peabody Museum of Archaeology and Ethnology, Harvard University. Living Tradition in Africa and the Americas: The Legacy of Melville J. & Frances S. Herskovits, 1998. Mary and Leigh Block Museum of Art, Northwestern University. Gupta, Sujata. "Profile of Jane Guyer". Proceedings of the National Academy of Sciences, February 14, 2012 vol. 109 no. 7, pp. 2181–2183. Biography at Johns Hopkins University A special issue of African Studies Review devoted to Marginal Gains

Désiré Mbonabucya

Désiré Mbonabucya is a Rwandan former professional association football forward. Mbonabucya was born in Rwanda, he was considered a valuable goalscorer for Sint-Truidense V. V. during his time at the club. After an injury, Mbonabucya moved to KVK Tienen. On 20 February 2009, he signed for US Albert in Schaerbeek. and eighteen months contract. Along with teammate Claude Kalisa, Mbonabucya forms the backbone of the Rwandan national team that participated in the 2004 African Nations Cup. Mbonabucya began his coaching career on 20 February 2009 as youth head coach for US Albert in Schaerbaek. Désiré Mbonabucya at National-Football-Teams.com Désiré Mbonabucya – FIFA competition record Désiré Mbonabucya at FootballDatabase.eu