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These drugs, and enzymeswill not be on the test. (excludingG-proteincoupledreceptorsof course).
Do NOT memorize these drugs,enzymesand pathologies. These are for reviewof the concepts.
Also,tryto refrainfromusinggoogle. All the answers canbe foundfairlyeasyif yougoogle them.
Parkinson’sdisease isthe neurodegenerative disease thatischaracterizedbythe deathof dopaminergic
neuronsinthe brain. The symptomsof Parkinson’sdiseaseare all movementrelatedissuessuchas
shaking,rigidity,andpossibly the completeinabilitytomove causedbylow dopamine levelsinrelated
synapses.
 Dopamine isa molecule (neurotransmitter) thatisusedforcommunicationfromone cell to
another.
 One treatmentforParkinson’sisthe combined administrationof Levodopa(L-DOPA) and
carbidopa.
o Levodopaisan inactive precursortodopamine thatisconvertedintoitsactive formby
Tyrosine hydroxylase.
o Carbidopaisan inhibitormoleculeforthe enzyme Tyrosinehydroxylase.
o Carbidopacannotcross the bloodbrainbarrier(forsimplicitiessake,let’ssayitcan’t
cross the cell membrane betweenthe circulatorysystemandthe brain)
 Tyrosine isfoundthroughoutthe bodyandnotjust withinthe brain.
 Tyrosine Hydroxylase:
o Under the influence of feedbackinhibitionof amolecule namedinthisdocument
What doesL in L-DOPA mean?
Why isthe L inL-DOPA importantforthisdrug?
What isthe substrate forTyrosine Hydroxylase?
What isthe productfor Tyrosine Hydroxylase?
Identifywhichmolecule isinvolvedinTyrosine Hydroxylase feedbackinhibition,andwhywould
feedbackinhibitionbe important oruseful forthe body.
Assumingdopamineisreleasedfromone cell,how isdopamine beingusedtocommunicate withthe
other?Explainhowdopamine wouldcommunicate withthe othercell. Itoccurs ina logical stepbystep
process.
Tyrosine hydroxylase doesnotworkwithoutthe presence of BH4,O2,andFe2+
. Knowingthatthese are
not alteredinthe enzymescatalyticactivity,whatcanwe refertothese as?
Alpha-methyl tyrosine isaninhibitorof thisenzyme. Asyoucan tell bythe name,it isverysimilarto
tyrosine. Whatkindof inhibitionmightthiscause andif youincreasedthe amountof substrate,could
the effectsof thisinhibitorbe negated?
In the presence of a ProteinKinase A (PKA)thisproteinhasincreasedactivity. What isPKA doing?
Draw twolinesonthiskineticsgraph. One indicatinghow the enzymewouldactwithoutaninhibitor
and one indicatinghowitmightreactwitheither feedbackinhibitionorthe above inhibitor.
Alsolabel Vmax onyourgraph.
Rate of reaction
Concentrationof substrate
Assumingthatthe distributionof dopamine andL-DOPA inthispicture iscorrect,why mightthisbe?
*the structuresare shownfora reason
Justfor completenesssake,I’llexplaincarbidopa. Carbidopaisaninhibitorof tyrosine hydroxylase
whichseemscounterintuitive since we wanttyrosine hydroxylasetoturnL-DOPA intodopamine.
Dopamine isactuallysensedbythe chemoreceptortriggerzone (CTZ) foundsomewhereinourbodies.
(I’mnot sure where) Whenthe CTZis triggered,thiscausesvomiting. Carbidopa,unlike L-DOPA,cannot
cross the bloodbrainbarriertherefore the tyrosinehydroxylase will notbe inhibitedinthe brain.
So essentiallywhatthe combineddrugsL-DOPA andcarbidopaare doingis:
 L-DOPA can go anywhere itpleases. Itacts as the startingmaterial fordopamine
 Carbidopainhibitstyrosine hydroxylaseenzymesonlyinthe bloodstream preventingthe
creationof dopamine thatistoxicinthe wrongportionsof our body.
 L-DOPA isconvertedintodopamine inthe brainproducingatherapeuticeffectwiththose with
Parkinson’s.
 Dopamine cannotcrossthe bloodbrainbarrier. Thisprevents itstoxiceffectsinotherpartsin
the bodyand localizeditstherapeuticeffectinthe brain.
As mentionedbefore,dopamine isaneurotransmitter. A dopamine synapse isdiagrammedbelow.
Dopamine (DA) isreleasedfromcell 1intothe space betweenthe twocells.(synapse=space betweento
neurons) DA can bindto one of two differentkindof receptors. Onreceptorisoncell 1, the other
receptorison cell two. Both of these receptorsare G-proteincoupledreceptors. The receptoroncell 1
isexactlythe same as the example showninclass. Itspathwayactivatesadenylyl cyclase. Describe this
pathway.
1. Dopamine bindstothe G proteincoupledreceptoroncell 2.
2. Exchange________________________________________________
________________________________________________________
________________________________________________________
3. G protein________________________________________________
________________________________________________________
________________________________________________________
4. Activation of____________________________by_____________
________________________________________________________
________________________________________________________
_______________________________________________________
5. Adenylyl cyclase________________________________________
________________________________________________________
________________________________________________________
_______

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BIOC 2011 TH

  • 1. These drugs, and enzymeswill not be on the test. (excludingG-proteincoupledreceptorsof course). Do NOT memorize these drugs,enzymesand pathologies. These are for reviewof the concepts. Also,tryto refrainfromusinggoogle. All the answers canbe foundfairlyeasyif yougoogle them. Parkinson’sdisease isthe neurodegenerative disease thatischaracterizedbythe deathof dopaminergic neuronsinthe brain. The symptomsof Parkinson’sdiseaseare all movementrelatedissuessuchas shaking,rigidity,andpossibly the completeinabilitytomove causedbylow dopamine levelsinrelated synapses.  Dopamine isa molecule (neurotransmitter) thatisusedforcommunicationfromone cell to another.  One treatmentforParkinson’sisthe combined administrationof Levodopa(L-DOPA) and carbidopa. o Levodopaisan inactive precursortodopamine thatisconvertedintoitsactive formby Tyrosine hydroxylase. o Carbidopaisan inhibitormoleculeforthe enzyme Tyrosinehydroxylase. o Carbidopacannotcross the bloodbrainbarrier(forsimplicitiessake,let’ssayitcan’t cross the cell membrane betweenthe circulatorysystemandthe brain)  Tyrosine isfoundthroughoutthe bodyandnotjust withinthe brain.  Tyrosine Hydroxylase: o Under the influence of feedbackinhibitionof amolecule namedinthisdocument What doesL in L-DOPA mean? Why isthe L inL-DOPA importantforthisdrug? What isthe substrate forTyrosine Hydroxylase? What isthe productfor Tyrosine Hydroxylase? Identifywhichmolecule isinvolvedinTyrosine Hydroxylase feedbackinhibition,andwhywould feedbackinhibitionbe important oruseful forthe body. Assumingdopamineisreleasedfromone cell,how isdopamine beingusedtocommunicate withthe other?Explainhowdopamine wouldcommunicate withthe othercell. Itoccurs ina logical stepbystep process.
  • 2. Tyrosine hydroxylase doesnotworkwithoutthe presence of BH4,O2,andFe2+ . Knowingthatthese are not alteredinthe enzymescatalyticactivity,whatcanwe refertothese as? Alpha-methyl tyrosine isaninhibitorof thisenzyme. Asyoucan tell bythe name,it isverysimilarto tyrosine. Whatkindof inhibitionmightthiscause andif youincreasedthe amountof substrate,could the effectsof thisinhibitorbe negated? In the presence of a ProteinKinase A (PKA)thisproteinhasincreasedactivity. What isPKA doing? Draw twolinesonthiskineticsgraph. One indicatinghow the enzymewouldactwithoutaninhibitor and one indicatinghowitmightreactwitheither feedbackinhibitionorthe above inhibitor. Alsolabel Vmax onyourgraph. Rate of reaction Concentrationof substrate Assumingthatthe distributionof dopamine andL-DOPA inthispicture iscorrect,why mightthisbe? *the structuresare shownfora reason
  • 3. Justfor completenesssake,I’llexplaincarbidopa. Carbidopaisaninhibitorof tyrosine hydroxylase whichseemscounterintuitive since we wanttyrosine hydroxylasetoturnL-DOPA intodopamine. Dopamine isactuallysensedbythe chemoreceptortriggerzone (CTZ) foundsomewhereinourbodies. (I’mnot sure where) Whenthe CTZis triggered,thiscausesvomiting. Carbidopa,unlike L-DOPA,cannot cross the bloodbrainbarriertherefore the tyrosinehydroxylase will notbe inhibitedinthe brain. So essentiallywhatthe combineddrugsL-DOPA andcarbidopaare doingis:  L-DOPA can go anywhere itpleases. Itacts as the startingmaterial fordopamine  Carbidopainhibitstyrosine hydroxylaseenzymesonlyinthe bloodstream preventingthe creationof dopamine thatistoxicinthe wrongportionsof our body.  L-DOPA isconvertedintodopamine inthe brainproducingatherapeuticeffectwiththose with Parkinson’s.  Dopamine cannotcrossthe bloodbrainbarrier. Thisprevents itstoxiceffectsinotherpartsin the bodyand localizeditstherapeuticeffectinthe brain. As mentionedbefore,dopamine isaneurotransmitter. A dopamine synapse isdiagrammedbelow. Dopamine (DA) isreleasedfromcell 1intothe space betweenthe twocells.(synapse=space betweento neurons) DA can bindto one of two differentkindof receptors. Onreceptorisoncell 1, the other receptorison cell two. Both of these receptorsare G-proteincoupledreceptors. The receptoroncell 1 isexactlythe same as the example showninclass. Itspathwayactivatesadenylyl cyclase. Describe this pathway. 1. Dopamine bindstothe G proteincoupledreceptoroncell 2. 2. Exchange________________________________________________ ________________________________________________________ ________________________________________________________ 3. G protein________________________________________________ ________________________________________________________ ________________________________________________________ 4. Activation of____________________________by_____________ ________________________________________________________ ________________________________________________________ _______________________________________________________ 5. Adenylyl cyclase________________________________________ ________________________________________________________ ________________________________________________________ _______