Basic Concept of Neurotransmitter Biochemistry (PDF) 2024

for undergraduate 2024 Basic Concept of Neurotransmitter Biochemistry Karismananda Department of Biochemistry Faculty of Medicine Hasanuddin University Learning Objectives U...

for undergraduate 2024 Basic Concept of Neurotransmitter Biochemistry Karismananda Department of Biochemistry Faculty of Medicine Hasanuddin University Learning Objectives Understanding the concept of neurotransmission in synapse Understanding the characteristic and metabolism of some of major neurotransmitters (NT) Knowing applications of neurotransmission in clinical setting What happens in depression? Mood Energy Sleep etc Impulses in brain?  Each parts of the brain is responsible for different types of motoric, sensorics and emotional functions Most of these area are excited by impulses  neurotransmitters (NT) What are NT actually? Synapses make NT necessary for signal transductions Neurotransmitters are chemical messengers that transmit signals across the synaptic cleft between neurons in the nervous system.  Do all synapses require NT? Some synapse are tightly connected that the impulse/electricity are transmitted directly to their neighbouring nervous cell This synapse is called Electrical Synapse Pereda, A. Electrical synapses and their functional interactions with chemical synapses. Nat Rev Neurosci 15, 250–263 (2014). https://doi.org/10.1038/nrn3708 What happens in anxiety people? Too much impulses? No inhibition to impulses? Types of Neurotransmitter effect There are three types of possible NT effect: 1. Excitatory 2. Inhibitory 3. Excitatory and inhibitory Inhibitory and excitatory NT Inhibitory or excitatory effect of NT depends on theirs specific receptors  one NT can have many receptors One type of NT (e.g. dopamine) can have many receptors that have different effect Excitatory  d1 Inhibitory  d2 (can be also excitatory depends on it location and context) dopamine How quick NTs can have effects? Although not as fast as in electric synapse, NT can also have immediate effect, or it may take longer time to have effect It relatively same quantity of impulse, how fast NT can have effects is based on the type of theirs receptor in post- histamine synapse  Ionotropic and Metabotropic NT Receptor Ionotropic  ligand-gated ion channels  immediate transmission Metabotropic  g- protein-coupled receptors  modulated (longer) transmission Jue SG. Characterizing Neurotransmitter Receptor Activation with a Perturbation Based Decomposition Method. June 2016. doi:10.15368/theses.2016.98 How long NTs effect last? Longevity of NTs are depends on several factors that strongly related to their metabolism General Concept of NTs metabolism Stage 1 & 2: NT production: accumulation of precursor and maturation Stage 3: packed to vesicles Stage 4 & 5: released to post- synapse receptors (4) or auto- receptors (5) Stage 6 – 9: termination  reuptake (post synapse or glial cell), degradation (enzymatic), diffuse out side cleft NT-related drugs will affect one or more of these mechanims  Degradation and diffusion depends on the NT structure Higher/more complex the structure, more resistant the NTs to degradation Biogenic Amino acids neuropeptides (monoamine) Much simpler Need to reuptake first larger molecules Have synaptic before degraded  No reuptake enzymatic (transporters) degradation  Relay on process1 degradation but much slower Qayyum A, Zai CC, Hirata Y, Tiwari AK, Cheema S, Nowrouzi B, Beitchman JH, Kennedy JL. The Role of the Catechol-o-Methyltransferase (COMT) GeneVal158Met in Aggressive Behavior, a Review of Genetic Studies. Curr Neuropharmacol. 2015;13(6):802-14. doi: 10.2174/1570159x13666150612225836. PMID: 26630958; PMCID: PMC4759319. E.g. Monoamine NT: Dopamine degradation Dopamine is monoamine NT Due to its smaller structure, it can be easily degraded and transported back It also can relatively easy diffuse outside the cleft Dopamine is degraded by monoamine oxidase (MAO) and catechol-O methyl transferase to (COMT)  homovalinic acid (HVA)  Amino acids NT: GABA (Gamma- Aminobutyric Acid) Glutamate and GABA (Gamma-Aminobutyric Acid) need to be reuptaken back (No. synaptic degradation)  Why the signal/NT can affect a lot of area in brain at once? Why also is diffusely detected in many areas in brain?1 Why also depressed person have symptom in gastrointestinal tract such as constipation? Akbari, Hesam & Sadiq, Muhammad Tariq & Rehman, Ateeq. (2021). Classification of normal and depressed EEG signals based on centered correntropy of rhythms in empirical wavelet transform domain. Health Information Science and Systems. 9. 10.1007/s13755-021-00139-7  Neuromodulators Volume transmission Modulate/alter effectiveness of NT Neurotransmitters can travels outside signalling synaptic cleft. Therefore it can be Bind on metabotropic categorized as: receptors 1. Neurotransmitters 2. Neuromodulators 3. Neurohormones Neurohormones Travels far through bloodstream Longer half-life Longer effect  Group Assignment 1. Make one poster/slide (in landscape) Group: 1. Serotonin  anxiety  SSRi about metabolism and related 2. Acethylcholine  myestenia gravis disease of the NT for each group  Acetylcholinesterase Inhibitors 3. Glycine  tetanus  GABA-agonist 2. In the slide should include: 4. Glutamate  autism  glutamate receptor anatagonist 1. Types, receptor, and structure 5. Norephineprine 2. Figure/graphic: metabolism in a 6. Dopamine disease 7. GABA  eplilepsy seizures  GABA Transaminase Inhibitors 3. Impotant clinical aspects (can be precursor, receptors, enzymes, etc) 4. Mechanism of the drug for that disease Big picture Why neurotransmitters are necessary? 1. Diversity and Complexity: The nervous system requires a wide range of signaling mechanisms to perform its various functions, which chemical synapses facilitate. 2. Regulation and Plasticity: The ability to modulate and adapt synaptic connections is essential for higher brain functions like learning, memory, and complex behaviors. 3. Adaptability: Neurotransmitters allow the nervous system to adapt to different circumstances and stimuli, offering a greater degree of control over physiological processes. Summary 1. Synaptic cleft requires neurotransmitters for impuls propagation 2. The propogation which can be either exicatory and inhibitory 3. the types of NT post-synaptic receptors can influnce the effect time of the NT 4. The metabolisms and structures of NT govern the duration of NT and medication associated to the NT-related diseases