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Dopamine & levodopa

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DOPAMINE AND L-DOPA

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Dopamine & levodopa

  1. 1. Dopamine & Levodopa Biochemistry Case 4 PBL G 5
  2. 2. Objectives Define the Dopamine. Explain the Synthesis of Dopamine and describe its mechanism. Explain what cause the deficiency of Dopamine. Define the Levodopa. Describe the conversion of Levodopa to Dopamine. Clarify the relationship between Dopamine and Levodopa
  3. 3. DEFINITION OF DOPAMINE Dopamine is a neurotransmitter, a chemical responsible for sending messages between the brain and different nerve cells of the body. Over the past 60 years, dopamine has been studied extensively and has been written about in over 110,000 research articles, mainly identifying its relationship with Parkinson's disease, drug addiction and mood disorders. At the same time, it has been at the forefront of controversy within the psychological and neuroscience fields.
  4. 4. FUNCTIONS OF DOPAMINE ● The main structure in your brain that controls all sorts of bodily movements is the basal ganglia ● In the prefrontal cortex, the main part of the brain associated with higher- order thinking, dopamine secretions help to improve your working memory. ● Dopamine allows you to keep focused and pay attention. ● Dopamine is the central chemical in your brain that regulates how you perceive and experience pleasure ● Along with exciting experiences, dopamine is also released when you encounter unwanted or aversive stimuli, like when you receive a paper cutI or you get into a messy argument with your best friend.
  5. 5. ● For most addiction-causing drugs, they work by targeting the dopamine neurotransmitters in your brain ● Dopamine that is released in the frontal lobes of the brain regulates the flow of information received from other areas of the brain. ● Increased levels of dopamine in the brain are associated with increased feelings of wakefulness. ● Because dopamine is the chemical that promotes feelings of pleasure, it makes us look forward to enjoying life and various activities.
  6. 6. Dopamine chemical structure Chemical Names: 4-(2-enezneb)lyhteonima-1,2-loid)CAPUI( 3,4- Dihydroxyphenethylamine Molecular Formula: C8H11NO2 Molecular Weight: 153.181g/mol
  7. 7. The Catecholamine Family ●L-dopa. ●Dopamine. ●Noradrenalin or Norepinephrine. ●Adrenalin or epinephrine.
  8. 8. Synthesis of Dopamine The direct precursor of dopamine, L-DOPA, can be synthesized indirectly from the essential amino acid phenylalanine or directly from the non-essential amino acid tyrosine.
  9. 9. Phenylalanine :- is an α-amino acid with the formula C9H11NO 2. It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine . Tyrosine :- 4- hydroxyphenylalanine eht fo eno si20 standard amino acids that are used by cells to synthesize proteins . L-DOPA :- L- 3,4-eninalalynehpyxordyhidna si amino acid that is made and used as part of the normal biology of humans, some animals and plants.
  10. 10. L-Phenylalanine is converted into L-tyrosine by the enzyme phenylalanine hydroxylase , with molecular oxygen (O 2) and tetrahydrobiopterin as cofactors.
  11. 11. Second step involve hydroxylation of tyrosine to Dihydroxyphenylalanine (L-DOPA) by enzyme tyrosine hydroxylase. Finally L-DOPA loses its a-carboxy group to form dopamine
  12. 12. Synthesis of Dopamine
  13. 13. Inactivation of Dopamine. The inactivation or breakdown of dopamine includes: Reuptake Enzymatic breakdown
  14. 14. Reuptake ➔ back to the presynaptic neuron eht aivdopamine transporter is the major role in the inactivation of dopamine neurotransmission. ➔ The recycled dopamine will face either breakdown by an enzyme or be re-packaged into vesicles and reused.
  15. 15. Enzymatic breakdown : In humans, dopamine breakdown has only one major metabolite Homovanillic acid. ➢ There are two major reactions in enzymatic degradation of dopamine which are catalysed by: Monoamine oxidase (MAO) Catechol-O-methyltransferase (COMT)
  16. 16. Parkinson’s disease Parkinson's disease (PD) is a chronic and progressive movement disorder, it involves the malfunction and death of vital nerve cells in the brain, called neurons . Parkinson's primarily affects neurons in an area of the brain called the substantia nigra . These neurons produce dopamine trap eht ot segassem sdnes taht lacimehc a , taht niarb eht focontrols movement and coordination. Parkinson's disease itself is not fatal . As It progresses niarb eht ni decudorp enimapod fo tnuoma eht , ,sesaercedot ytiliba ssel dna ssel sah nosrep a ,enimapod ssel dna ssel htiW
  17. 17. Deficiency of Dopamine (Parkinson’s SYMPTOMS) 1. Tremor or Shaking. 2.Loss of Smell. 3.Trouble Sleeping. 4.Trouble Moving or Walking. 5.Constipation. 6.Dizziness or Fainting. 7.Slowed movement (bradykinesia).
  18. 18. Levodopa A naturally-occurring amino acid found in food, converted into dopamine in the brain and body, and administered clinically in the management of Parkinson's disease and dopa-responsive dystonia.
  19. 19. Functions of Levodopa Levodopa is used alone or in combination with carbidopa to treat Parkinson's disease, sometimes referred to as shaking palsy. Some patients require the combination of medicine, while others benefit from levodopa alone. By improving muscle control, levodopa allows more normal movements of the body.
  20. 20. CHEMICAL STRUCTURE OF LEVODOPA )OH(2 C6H3CH2CH(NH 2OC)2 H
  21. 21. ● Parkinson patients are treated with L-dopa. ● In order to correct or minimize these complications, patients will need to increase dopamine production and/or release in the brain . ● Unfortunately, peripheral dopamine administration is not effective because dopamine cannot cross the blood brain barrier. Dopamine given as a drug does not directly affect the central nervous system . ● However, the precursor to dopamine, levodopa (L-Dopa; 3,4-lynehpyxordyhid-L- ni esu rof enimapod ot detrevnoc eb dna reirrab niarb doolb eht ssorc nac ,)eninala smotpmys eseht gnillortnoc. ● It is most commonly prescribed in a formulation that combines it with carbidopa The Conversion of Levodopa to Dopamine
  22. 22. ● L-DOPA is transported across the BBB by an amino acid transport system. ● Once across, L-DOPA is decarboxylated to dopamine by Dopa Decarboxylase (DDC). ● In actual practice, L-DOPA is almost always co-administered together with an inhibitor of aromatic L-amino acid decarboxylase, so it doesn’t get converted to dopamine before it crosses the BBB.(blood brain barrier) ● Once levodopa has entered the central nervous system (CNS), it is metabolized to dopamine by aromatic L-amino acid decarboxylase which is(apodibrac does not cross the BBB itself) ● Pyridoxal phosphate (vitamin B 6yam dna ,noitalyxobraced siht rof rotcafoc deriuqer a si ) enixodiryp sa yllausu ,apodovel htiw gnola deretsinimda eb ● The coadministration of carbidopa noitcudorp enimapod sevorpmi ylno ton apodovel htiw nehw gnitimov dna aesuan fo ecnedicni eht secuder yltnacifingis osla tub ,niarb eht ni enola deretsinimda gnieb apodovel ot derapmoc.
  23. 23. Why we don’t take Dopamine by itself? Dopamine is not effective because it cannot cross the blood brain barrier , The reason for its inability to cross the blood brain barrier has to do with at least two influencing factors: The first fo eerged retaerg a sah taht elucelom cilihpordyh a si enimapod taht si senarbmem llec gnissorc ni ytluciffid. The second doolb eht tsap teg ot enimapod rof retropsnart a fo ecnesba eht si niarb eht otni dna reirrab niarb.
  24. 24. The Relationship Between Dopamine and Levodopa Levodopa (L-dopa) is a drug that the brain converts into dopamine. The body metabolizes it to produce dopamine. The metabolism take place when the enzyme dopa decarboxylase (catalyze the removal of a carbon dioxide molecule from a compound.) in the periphery. It should not be taken with a high-protein diet. Levodopa is most commonly combined with carbidopa to prevent nausea and vomiting, allowing more levodopa to get to the brain. In sretne apodovel ,apodibrac fo ecneserp eht rof deen eht gnidiova suht ,setitinauq regral ni niarb eht apodovel fo sesod hgih ylevissecxe.
  25. 25. References ● Dopamine structure: https://pubchem.ncbi.nlm.nih.gov/compound/dopamine#section=Top ● Textbook of medical biochemistry, Third Edition, Page:294 ● The role of insulin signaling on dopamine transporter trafficking by nicole k. Speed. Pages 1-10. ● http://www.mayoclinic.org/diseases-conditions/parkinsons- disease/basics/symptoms/con-20028488 ● http://www.parkinson.org/understanding-parkinsons/ 10-ylrae-gninraw-sngis
  26. 26. Thank you PBL G5

Editor's Notes

  • also known as sapropterin, is a naturally occurring essential cofactor of the three aromatic amino acid hydroxylase enzymes, used in the degradation of amino acid phenylalanine and in the biosynthesis of the neurotransmitters serotonin (5-hydroxytryptamine, 5-HT), melatonin, dopamine, norepinephrine (noradrenaline), epinephrine (adrenaline), and is a cofactor for the production of nitric oxide (NO) by the nitric oxide synthases.[1] Chemically, its structure is that of a reduced pteridine derivative.
  • http://www.mayoclinic.org/diseases-conditions/parkinsons-disease/basics/symptoms/con-20028488
    http://www.parkinson.org/understanding-parkinsons/10-early-warning-signs
  • khadijas and hadezas part
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