Dopamine is a neurotransmitter that regulates movement, pleasure, and attention. It is synthesized from the amino acids phenylalanine and tyrosine. Dopamine deficiency due to loss of neurons in the substantia nigra causes Parkinson's disease symptoms like tremors and slowed movement. Levodopa is converted to dopamine in the brain to treat Parkinson's. However, dopamine cannot cross the blood brain barrier, so levodopa is used instead as it is converted to dopamine once inside the brain. Levodopa works together with carbidopa to maximize dopamine production in the brain and minimize side effects.

1. Dopamine & Levodopa
Biochemistry Case 4
PBL G 5

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. 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. 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. ● 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. 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. The Catecholamine Family
●L-dopa.
●Dopamine.
●Noradrenalin or Norepinephrine.
●Adrenalin or epinephrine.

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. 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. L-Phenylalanine is converted into L-tyrosine
by the enzyme phenylalanine hydroxylase ,
with molecular oxygen (O 2)
and tetrahydrobiopterin as cofactors.

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. Synthesis of Dopamine

13. Inactivation of Dopamine.
The inactivation or breakdown of dopamine includes:
Reuptake
Enzymatic breakdown

15. 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.

16. 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)

19. 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

21. 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).

22. 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.

23. 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.

24. CHEMICAL STRUCTURE OF LEVODOPA
)OH(2 C6H3CH2CH(NH 2OC)2 H

25. ● 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

26. ● 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.

29. 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.

30. 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.

31. 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

32. Thank you
PBL G5