Proteopedia - User contributions [en]

Carbidopa

2016-12-06T00:39:02Z

Andrew Warzinski:

==Carbidoba ((2S)-3-(3,4-dihydroxyphenyl)-2-hydrazinyl-2-methylpropanoic acid)==
<StructureSection load='1js3' size='340' side='right' caption='Crystal structure of DOPA Decarboxylase in complex with the inhibitor carbidopa (PDB Code [[1js3]])'>

== Function ==
<scene name='pdbligand=142:CARBIDOPA'>Carbidopa</scene> (Lodosyn) is a drug given, in conjunction with Levadopa, to those with Parkinson's Disease in order to inhibit the extracranial metabolism of Levadopa to dopamine, allowing a greater portion of the drug to cross the blood-brain barrier and produce the desired anti-parkinsonian effects in the nerve cell. It works by inhibiting the enzymatic activity of aromatic-L-amino-acid decarboxylase ([[DOPA Decarboxylase]] or DDC).<ref name="one">PMID:11106255</ref>

== Structure ==
[[Image:512px-Carbidopa.svg.png|thumb|right|2D Structure of Carbidopa]][[Image:800px-Carbidopa ball-and-stick.png|thumb|right|Ball and Stick Model of Carbidopa]]Carbidopa is an inhibitor of DDC. It is a partially water soluble, white, crystalline compound with a molecular weight of 226.232g/mol and a melting point of 208°C. Its empirical formula is C10H14N2O4•H2O and its IUPAC name is (2S)-3-(3,4-dihydroxyphenyl)-2-hydrazinyl-2-methylpropanoic acid. Used in conjunction with Levadopa (L-DOPA), a precursor to dopamine, it increases concentrations of L-DOPA in the brain. Due to the fact Carbidopa cannot cross the blood–brain barrier, it inhibits only peripheral DDC thus preventing the conversion of L-DOPA to dopamine outside of neuronal cells. This greatly lessens the side effects caused by dopamine on the periphery, as well as increasing the concentration of L-DOPA and subsequently dopamine in the brain.<ref name="two">https://pubchem.ncbi.nlm.nih.gov/compound/carbidopa</ref>

== Molecular Mechanism ==
The vitamin B6 (<scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>)-dependent enzyme DDC, an enzyme abundant in the nervous system as well as kidneys of humans, catalyzes the conversion of L-DOPA into dopamine.<ref name="three">PMID: 7651438</ref> The catalytically active form of DDC is a homodimer, a feature typical of this class of enzymes.<ref name= "four">PMID: 10673430</ref> DDCs active site is located between the two monomers but is mainly composed of residues from only one of the monomers. The cofactor <scene name='74/746001/Plp_binding/1'>PLP</scene> binds to Lys 303 through a Schiff base linkage and a salt bridge between the carboxylate group of Asp 271 and the protonated pyridine nitrogen of PLP, which acts as a strong electron sink capable of stabilizing the carbanionic intermediates produced by active DDC. Cofactor is further stabilized in the enzyme through a network of hydrogen bonds. Carbidopa works by forming a hydrazone linkage with the PLP cofactor through its hydrazine moiety and blocking the DDC <scene name='74/746001/Active_site_dopa_final/1'>active site</scene> residues Ile 101' and Phe 103' in the substrate binding pocket with its catechol ring.<ref name="five">doi:10.1038/nsb1101-963</ref> In addition, the 4' hydroxyl group of Carbidopas catechol ring hydrogen bonds with THR 82 and the carboxylate group binds to HIS 192, a highly-conserved residue in PLP-dependent decarboxylases.<ref name="six">PMID: 8889823</ref> Due to the fact that Carbidopa cannot cross the blood-brain barrier, its inhibiting effects only are displayed in the periphery.

==Interactions==
[[Image:Levodopa.png|thumb|left|2D Structure of Levodopa]][[Image:Dopamine.svg.png|thumb|left|2D Structure of Dopamine]]
Carbidopa interacts well with Levodopa (L-DOPA) and dopamine. Dopamine is essential when it comes to motor, cognitive, behavioral, endocrine functions, and even neuronal retinal development in the central nervous system.<ref name="seven">PMID:18828673</ref><ref name="eight">PMID:22131937</ref> Therefore,understanding the interactions between how Levodopa and dopamine affect the body can help understand why it pairs well with Carbidopa. Carbidopa works by inhibiting the enzyme activity of DDC, when both are working in the body it blocks the Levodopa negative side effects so the lipid soluble drug pair can now pass the blood-brain barrier where Carbidopa cannot. Carbidopa interects with Levodpa to reduce the side effects of because once Levodopa crosses the blood brain barrier it can help increase levels of dopamine to improve motor, cognitive, behavioral, endocrine functions, etc. Another likely interaction between dopamine and Carbidopa is the human peripheral blood lymphocytes. These blood lymphocytes supposedly synthesize dopamine through the tyrosine-hydroxylase/DOPA-decarboxylase pathway, and express dopamine receptors and dopamine transport on their plasma membrane.<ref name="eight">PMID:22131937</ref> Reports show changes in expression of this dopamine receptors and dopamine transport system in the peripheral blood lymphocytes, but since the Carbidopa can’t pass the blood brain barrier it needs to be paired to a lipid soluble chemical (Levodopa) until a different method is found.

== Disease in Humans ==
Parkinson's disease (PD) is a chronic, progressive neurological disease whose symptoms include bradykinesia, tremors, postural instability and rigidity. Although the exact cause of the disease is currently unknown, it is believed to be caused by the apoptosis of dopaminergic cells in the substantia nigra of the brain and subsequent loss of dopamine.<ref name="nine">PMID:10746727</ref> Carbidopa is used mostly for people with Parkinson’s disease, although it can be pair with other drugs to reduce symptoms of other known neurological diseases. According to the National Parkinson Foundation, Levodopa alone is known to cause nausea and vomiting in Parkinson’s patients, and Carbidopa prevents those side effects.<ref name="ten">http://www.parkinson.org/understanding-parkinsons/treatment/Medications-for-Motor-Symptoms/Carbidopa-levodopa</ref> Carbidopa can act as an enhancer for Levodopa by decreasing the dosage of Levodopa needed for Parkinson’s patients, up to 80%. It’s a inhibitor that is limited to extracerebral tissue, therefore Carbidopa with Levodopa leaves more Levodopa available for transport to the brain.<ref name="eleven">PMID:10939456</ref> Modern treatments like this are used for Parkinson’s disease today. A combined tablet of Carbidopa and Levodopa (Sinemet)are offered as immediate-release tablets and slow-release tablets, along with dissolvable tablets.<ref name="twelve">http://www.merck.com/product/home.html</ref>

</StructureSection>
== References ==
<references/>

Carbidopa

2016-11-16T18:42:03Z

Andrew Warzinski:

==Carbidoba ((2S)-3-(3,4-dihydroxyphenyl)-2-hydrazinyl-2-methylpropanoic acid)==
== Function ==
<StructureSection load='1js3'=size='340' side='right' caption='Crystal structure of DOPA Decarboxylase in complex with the inhibitor carbidopa (PDB Code:[[1js3]])' scene=''><scene name='pdbligand=142:CARBIDOPA'>Carbidopa</scene> (Lodosyn) is a drug given, in conjunction with Levadopa, to those with Parkinson's Disease in order to inhibit the extracranial metabolism of Levadopa to dopamine, allowing a greater portion of the drug to cross the blood-brain barrier and produce the desired anti-parkinsonian effects in the nerve cell. It works by inhibiting the enzymatic activity of aromatic-L-amino-acid decarboxylase ([[DOPA Decarboxylase]] or DDC)<ref name="one">PMID:11106255</ref>.

== Structure ==
[[Image:512px-Carbidopa.svg.png|thumb|right|2D Structure of Carbidopa]][[Image:800px-Carbidopa ball-and-stick.png|thumb|right|Ball and Stick Model of Carbidopa]]Carbidopa is an inhibitor of DDC. It is a partially water soluble, white, crystalline compound with a molecular weight of 226.232g/mol and a melting point of 208°C. Its empirical formula is C10H14N2O4•H2O and its IUPAC name is (2S)-3-(3,4-dihydroxyphenyl)-2-hydrazinyl-2-methylpropanoic acid. Used in conjunction with Levadopa (L-DOPA), a precursor to dopamine, it increases concentrations of L-DOPA in the brain. Due to the fact Carbidopa cannot cross the blood–brain barrier, it inhibits only peripheral DDC thus preventing the conversion of L-DOPA to dopamine outside of neuronal cells. This greatly lessens the side effects caused by dopamine on the periphery, as well as increasing the concentration of L-DOPA and subsequently dopamine in the brain.<ref name="two">https://pubchem.ncbi.nlm.nih.gov/compound/carbidopa#section=Top</ref>

== Molecular Mechanism ==
The conversion of L-DOPA into dopamine is catalyzed by the vitamin B6 (<scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>)-dependent enzyme DDC, an enzyme abundant in the nervous system as well as kidneys of humans<ref name="three">PMID: 7651438</ref> The catalytically active form of DDC is a homodimer, a feature typical of this class of enzymes<ref name= "four">PMID: 10673430</ref>. DDCs active site is located between the two monomers but is mainly composed of residues from only one of the monomers. The cofactor PLP binds to Lys 303 through a Schiff base linkage and a salt bridge between the carboxylate group of Asp 271 and the protonated pyridine nitrogen of PLP, which acts as a strong electron sink capable of stabilizing the carbanionic intermediates produced by active DDC. the cofactor is further stabilized in the enzyme through a network of hydrogen bonds. Carbidopa works by forming a hydrazone linkage with the PLP cofactor through its hydrazine moiety and blocking the DDC <scene name='74/746001/Active_site_dopa_final/1'>active site</scene> residues Ile 101' and Phe 103' in the substrate binding pocket with its catechol ring<ref name="five">doi:10.1038/nsb1101-963</ref>. In addition, the 4' hydroxyl group of Carbidopas catechol ring hydrogen bonds with THR 82 and the carboxylate group binds to HIS 192, a highly-conserved residue in PLP-dependent decarboxylases.<ref name="six">PMID: 8889823</ref> Due to the fact that Carbidopa cannot cross the blood-brain barrier, its inhibiting effects only are displayed in the periphery.

== Disease in Humans ==
Parkinson's disease (PD) is a chronic, progressive neurological disease whose symptoms include bradykinesia, tremors, postural instability and rigidity. Although the exact cause of the disease is currently unknown, it is believe to be caused by the apoptosis of dopanergic cells in the substantia nigra of the brain and subsequent loss of dopamine.<ref name="seven">PMID:10746727</ref>

</StructureSection>
== References ==
<references/>

Carbidopa

2016-11-16T18:34:56Z

Andrew Warzinski:

== Function ==
<StructureSection load='1js3'=size='340' side='right' caption='Crystal structure of DOPA Decarboxylase in complex with the inhibitor carbidopa PDB:[[1js3]]' scene=''><scene name='pdbligand=142:CARBIDOPA'>Carbidopa</scene> (Lodosyn) is a drug given, in conjunction with Levadopa, to those with Parkinson's Disease in order to inhibit the extracranial metabolism of Levadopa to dopamine, allowing a greater portion of the drug to cross the blood-brain barrier and produce the desired anti-parkinsonian effects in the nerve cell. It works by inhibiting the enzymatic activity of aromatic-L-amino-acid decarboxylase ([[DOPA Decarboxylase]] or DDC)<ref name="one">PMID:11106255</ref>.

== Structure ==
[[Image:512px-Carbidopa.svg.png|thumb|right|2D Structure of Carbidopa]][[Image:800px-Carbidopa ball-and-stick.png|thumb|right|Ball and Stick Model of Carbidopa]]Carbidopa is an inhibitor of DDC. It is a partially water soluble, white, crystalline compound with a molecular weight of 226.232g/mol and a melting point of 208°C. Its empirical formula is C10H14N2O4•H2O and its IUPAC name is (2S)-3-(3,4-dihydroxyphenyl)-2-hydrazinyl-2-methylpropanoic acid. Used in conjunction with Levadopa (L-DOPA), a precursor to dopamine, it increases concentrations of L-DOPA in the brain. Due to the fact Carbidopa cannot cross the blood–brain barrier, it inhibits only peripheral DDC thus preventing the conversion of L-DOPA to dopamine outside of neuronal cells. This greatly lessens the side effects caused by dopamine on the periphery, as well as increasing the concentration of L-DOPA and subsequently dopamine in the brain.<ref name="two">https://pubchem.ncbi.nlm.nih.gov/compound/carbidopa#section=Top</ref>

== Molecular Mechanism ==
The conversion of L-DOPA into dopamine is catalyzed by the vitamin B6 (<scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>)-dependent enzyme DDC, an enzyme abundant in the nervous system as well as kidneys of humans<ref name="three">PMID: 7651438</ref> The catalytically active form of DDC is a homodimer, a feature typical of this class of enzymes<ref name= "four">PMID: 10673430</ref>. DDCs active site is located between the two monomers but is mainly composed of residues from only one of the monomers. The cofactor PLP binds to Lys 303 through a Schiff base linkage and a salt bridge between the carboxylate group of Asp 271 and the protonated pyridine nitrogen of PLP, which acts as a strong electron sink capable of stabilizing the carbanionic intermediates produced by active DDC. the cofactor is further stabilized in the enzyme through a network of hydrogen bonds. Carbidopa works by forming a hydrazone linkage with the PLP cofactor through its hydrazine moiety and blocking the DDC <scene name='74/746001/Active_site_dopa_final/1'>active site</scene> residues Ile 101' and Phe 103' in the substrate binding pocket with its catechol ring<ref name="five">doi:10.1038/nsb1101-963</ref>. In addition, the 4' hydroxyl group of Carbidopas catechol ring hydrogen bonds with THR 82 and the carboxylate group binds to HIS 192, a highly-conserved residue in PLP-dependent decarboxylases.<ref name="six">PMID: 8889823</ref> Due to the fact that Carbidopa cannot cross the blood-brain barrier, its inhibiting effects only are displayed in the periphery.

== Disease in Humans ==
Parkinson's disease (PD) is a chronic, progressive neurological disease whose symptoms include bradykinesia, tremors, postural instability and rigidity. Although the exact cause of the disease is currently unknown, it is believe to be caused by the apoptosis of dopanergic cells in the substantia nigra of the brain and subsequent loss of dopamine.<ref name="seven">PMID:10746727</ref>

</StructureSection>
== References ==
<references/>

Carbidopa

2016-11-16T18:34:39Z

Andrew Warzinski:

== Function ==
<StructureSection load='1js3'=size='340' side='right' caption='Crystal structure of DOPA Decarboxylase in complex with the inhibitor carbidopa PDB:[[1js3]]' scene=''><scene name='pdbligand=142:CARBIDOPA'>Carbidopa</scene> (Lodosyn) is a drug given, in conjunction with Levadopa, to those with Parkinson's Disease in order to inhibit the extracranial metabolism of Levadopa to dopamine, allowing a greater portion of the drug to cross the blood-brain barrier and produce the desired anti-parkinsonian effects in the nerve cell. It works by inhibiting the enzymatic activity of aromatic-L-amino-acid decarboxylase ([[DOPA Decarboxylase]] or DDC)<ref name="one">PMID:11106255</ref>.

== Structure ==
[[Image:512px-Carbidopa.svg.png|thumb|right|2D Structure of Carbidopa]]Carbidopa is an inhibitor of DDC. It is a partially water soluble, white, crystalline compound with a molecular weight of 226.232g/mol and a melting point of 208°C. Its empirical formula is C10H14N2O4•H2O and its IUPAC name is (2S)-3-(3,4-dihydroxyphenyl)-2-hydrazinyl-2-methylpropanoic acid. Used in conjunction with Levadopa (L-DOPA), a precursor to dopamine, it increases concentrations of L-DOPA in the brain. Due to the fact Carbidopa cannot cross the blood–brain barrier, it inhibits only peripheral DDC thus preventing the conversion of L-DOPA to dopamine outside of neuronal cells. This greatly lessens the side effects caused by dopamine on the periphery, as well as increasing the concentration of L-DOPA and subsequently dopamine in the brain.<ref name="two">https://pubchem.ncbi.nlm.nih.gov/compound/carbidopa#section=Top</ref>

== Molecular Mechanism ==
The conversion of L-DOPA into dopamine is catalyzed by the vitamin B6 (<scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>)-dependent enzyme DDC, an enzyme abundant in the nervous system as well as kidneys of humans<ref name="three">PMID: 7651438</ref> The catalytically active form of DDC is a homodimer, a feature typical of this class of enzymes<ref name= "four">PMID: 10673430</ref>. DDCs active site is located between the two monomers but is mainly composed of residues from only one of the monomers. The cofactor PLP binds to Lys 303 through a Schiff base linkage and a salt bridge between the carboxylate group of Asp 271 and the protonated pyridine nitrogen of PLP, which acts as a strong electron sink capable of stabilizing the carbanionic intermediates produced by active DDC. the cofactor is further stabilized in the enzyme through a network of hydrogen bonds. Carbidopa works by forming a hydrazone linkage with the PLP cofactor through its hydrazine moiety and blocking the DDC <scene name='74/746001/Active_site_dopa_final/1'>active site</scene> residues Ile 101' and Phe 103' in the substrate binding pocket with its catechol ring<ref name="five">doi:10.1038/nsb1101-963</ref>. In addition, the 4' hydroxyl group of Carbidopas catechol ring hydrogen bonds with THR 82 and the carboxylate group binds to HIS 192, a highly-conserved residue in PLP-dependent decarboxylases.<ref name="six">PMID: 8889823</ref> Due to the fact that Carbidopa cannot cross the blood-brain barrier, its inhibiting effects only are displayed in the periphery.

== Disease in Humans ==
Parkinson's disease (PD) is a chronic, progressive neurological disease whose symptoms include bradykinesia, tremors, postural instability and rigidity. Although the exact cause of the disease is currently unknown, it is believe to be caused by the apoptosis of dopanergic cells in the substantia nigra of the brain and subsequent loss of dopamine.<ref name="seven">PMID:10746727</ref>

</StructureSection>
== References ==
<references/>

Carbidopa

2016-11-16T18:03:17Z

Andrew Warzinski:

Carbidopa

2016-11-16T17:43:30Z

Andrew Warzinski:

== Function ==
<StructureSection load='1js3'=size='340' side='right' caption='Crystal structure of DOPA Decarboxylase in complex with the inhibitor carbidopa PDB:[[1js3]]' scene=''><scene name='pdbligand=142:CARBIDOPA'>Carbidopa</scene> (Lodosyn) is a drug given, in conjunction with Levadopa, to those with Parkinson's Disease in order to inhibit the extracranial metabolism of Levadopa to dopamine, allowing a greater portion of the drug to cross the blood-brain barrier and produce the desired anti-parkinsonian effects in the nerve cell. It works by inhibiting the enzymatic activity of aromatic-L-amino-acid decarboxylase ([[DOPA Decarboxylase]] or DDC)<ref name="one">PMID:11106255</ref>.

== Structure ==
[[Image:512px-Carbidopa.svg.png|thumb|left|2D Structure of Carbidopa]][[Image:800px-Carbidopa ball-and-stick.png|thumb|left|Ball and Stick Model of Carbidopa]]Carbidopa is an inhibitor of DDC. It is a partially water soluble, white, crystalline compound with a molecular weight of 226.232g/mol and a melting point of 208°C. Its empirical formula is C10H14N2O4•H2O and its IUPAC name is (2S)-3-(3,4-dihydroxyphenyl)-2-hydrazinyl-2-methylpropanoic acid. Used in conjunction with Levadopa (L-DOPA), a precursor to dopamine, it increases concentrations of L-DOPA in the brain. Due to the fact Carbidopa cannot cross the blood–brain barrier, it inhibits only peripheral DDC thus preventing the conversion of L-DOPA to dopamine outside of neuronal cells. This greatly lessens the side effects caused by dopamine on the periphery, as well as increasing the concentration of L-DOPA and subsequently dopamine in the brain.<ref name="two">https://pubchem.ncbi.nlm.nih.gov/compound/carbidopa#section=Top</ref>

== Molecular Mechanism ==
The conversion of L-DOPA into dopamine is catalyzed by the vitamin B6 (<scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>)-dependent enzyme DDC, an enzyme abundant in the nervous system as well as kidneys of humans<ref name="three">PMID: 7651438</ref> The catalytically active form of DDC is a homodimer, a feature typical of this class of enzymes<ref name= "four">PMID: 10673430</ref>. DDCs active site is located between the two monomers but is mainly composed of residues from only one of the monomers. The cofactor PLP binds to Lys 303 through a Schiff base linkage and a salt bridge between the carboxylate group of Asp 271 and the protonated pyridine nitrogen of PLP, which acts as a strong electron sink capable of stabilizing the carbanionic intermediates produced by active DDC. the cofactor is further stabilized in the enzyme through a network of hydrogen bonds. Carbidopa works by forming a hydrazone linkage with the PLP cofactor through its hydrazine moiety and blocking the DDC <scene name='74/746001/Active_site_dopa/4'>active site</scene> residues Ile 101' and Phe 103' in the substrate binding pocket with its catechol ring<ref name="five">doi:10.1038/nsb1101-963</ref>. Due to the fact that Carbidopa cannot cross the blood-brain barrier, its inhibiting effects only are displayed in the periphery.

== Disease in Humans ==
Parkinson's disease (PD) is a chronic, progressive neurological disease whose symptoms include bradykinesia, tremors, postural instability and rigidity. Although the exact cause of the disease is currently unknown, it is believe to be caused by the apoptosis of dopanergic cells in the substantia nigra of the brain and subsequent loss of dopamine.<ref name="six">PMID:10746727</ref>

</StructureSection>
== References ==
<references/>

Carbidopa

2016-11-16T17:30:25Z

Andrew Warzinski:

== Function ==
<StructureSection load='1js3'=size='340' side='right' caption='Crystal structure of DOPA Decarboxylase in complex with the inhibitor carbidopa PDB:[[1js3]]' scene=''><scene name='pdbligand=142:CARBIDOPA'>Carbidopa</scene> (Lodosyn) is a drug given, in conjunction with Levadopa, to those with Parkinson's Disease in order to inhibit the extracranial metabolism of Levadopa to dopamine, allowing a greater portion of the drug to cross the blood-brain barrier and produce the desired anti-parkinsonian effects. It works by inhibiting the enzymatic activity of aromatic-L-amino-acid decarboxylase ([[DOPA Decarboxylase]] or DDC)<ref name="one">PMID:11106255</ref>

== Structure ==
[[Image:512px-Carbidopa.svg.png|thumb|left|2D Structure of Carbidopa]][[Image:800px-Carbidopa ball-and-stick.png|thumb|left|Ball and Stick Model of Carbidopa]]Carbidopa is an inhibitor of DDC. It is a partially water soluble, white, crystalline compound with a molecular weight of 226.232g/mol and a melting point of 208°C. Its empirical formula is C10H14N2O4•H2O and its IUPAC name is (2S)-3-(3,4-dihydroxyphenyl)-2-hydrazinyl-2-methylpropanoic acid. Used in conjunction with Levadopa (L-DOPA), a precursor to dopamine, it increases concentrations of L-DOPA in the brain. Due to the fact Carbidopa cannot cross the blood–brain barrier, it inhibits only peripheral DDC thus preventing the conversion of L-DOPA to dopamine outside of neuronal cells. This greatly lessens the side effects caused by dopamine on the periphery, as well as increasing the concentration of L-DOPA and subsequently dopamine in the brain.<ref name="two">https://pubchem.ncbi.nlm.nih.gov/compound/carbidopa#section=Top</ref>

== Molecular Mechanism ==
The conversion of L-DOPA into dopamine is catalyzed by the vitamin B6 (<scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>)-dependent enzyme DDC, an enzyme abundant in the nervous system as well as kidneys of humans<ref name="three">PMID: 7651438</ref> The catalytically active form of DDC is a homodimer, a feature typical of this class of enzymes<ref name= "four">PMID: 10673430</ref>. DDCs active site is located between the two monomers but is composed mainly of residues from only one of the monomers. The cofactor PLP binds to Lys 303 through a Schiff base linkage and a salt bridge between the carboxylate group of Asp 271 and the protonated pyridine nitrogen of PLP, which is able to provide a strong electron sink capable of stabilizing the carbanionic intermediates produced by active DDC. Carbidopa works by forming a hydrazone linkage with the PLP cofactor through its hydrazine moiety and blocking the DDC <scene name='74/746001/Active_site_dopa/4'>active site</scene> residues Ile 101' and Phe 103' in the substrate binding pocket with its catechol ring<ref name="five">doi:10.1038/nsb1101-963</ref>. Due to the fact that Carbidopa cannot cross the blood-brain barrier, its inhibiting effects only are displayed in the periphery.

== Disease in Humans ==
Parkinson's disease (PD) is a chronic, progressive neurological disease whose symptoms include bradykinesia, tremors, postural instability and rigidity. Although the exact cause of the disease is currently unknown, it is believe to be caused by the apoptosis of dopanergic cells in the substantia nigra of the brain and subsequent loss of dopamine.<ref name="six">PMID:10746727</ref>

</StructureSection>
== References ==
<references/>

Carbidopa

2016-11-16T03:13:06Z

Andrew Warzinski:

== Carbidopa ==
<StructureSection load='1js3' size='340' side='right' caption='Crystal structure of DOPA Decarboxylase in complex with the inhibitor carbidopa PDB:[[1js3]]' scene=''><scene name='pdbligand=142:CARBIDOPA'>Carbidopa</scene> (Lodosyn) is a drug given, in conjunction with Levadopa, to those with Parkinson's Disease in order to inhibit the peripheral metabolism of Levadopa, allowing a greater portion of the drug to cross the blood-brain barrier and produce the desired effect on the central nervous system. It works by inhibiting the enzymatic activity of aromatic-L-amino-acid decarboxylase ([[DOPA Decarboxylase]] or DDC)<ref name="one">PMID:11106255</ref>

== Molecular Mechanism ==
The conversion of L-DOPA into dopamine is catalyzed by the vitamin B6 (<scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>)-dependent enzyme DDC, an enzyme abundant in the nervous system as well as kidneys of humans<ref name="two">PMID: 7651438</ref> The catalytically active form of DDC is a homodimer, a feature typical of this class of enzymes<ref name= "three">PMID: 10673430</ref>. DDCs active site is located between the two monomers but is composed mainly of residues from only one of the monomers. The cofactor PLP binds to Lys 303 through a Schiff base linkage and a salt bridge between the carboxylate group of Asp 271 and the protonated pyridine nitrogen of PLP, which is able to provide a strong electron sink capable of stabilizing the carbanionic intermediates produced by active DDC. Carbidopa works by forming a hydrazone linkage with the PLP cofactor through its hydrazine moiety and blocking the DDC <scene name='74/746001/Active_site_dopa/4'>active site</scene> residues Ile 101' and Phe 103' in the substrate binding pocket with its catechol ring<ref name="four">doi:10.1038/nsb1101-963</ref>. Due to the fact that Carbidopa cannot cross the blood-brain barrier, its inhibiting effects only are displayed in the periphery.
== Structural highlights ==
[[Image:512px-Carbidopa.svg.png|thumb|left|2D Structure of Carbidopa]][[Image:800px-Carbidopa ball-and-stick.png|thumb|left|Ball and Stick Model of Carbidopa]]Carbidopa is an inhibitor of DDC. It is a partially water soluble, white, crystalline compound with a molecular weight of 226.232g/mol. Its empirical formula is C10H14N2O4•H2O and its IUPAC name is (2S)-3-(3,4-dihydroxyphenyl)-2-hydrazinyl-2-methylpropanoic acid. Used in conjunction with Levadopa (L-DOPA), a precursor to dopamine, it increases concentrations of L-DOPA in the brain. Due to the fact Carbidopa cannot cross the blood–brain barrier, it inhibits only peripheral DDC thus preventing the conversion of L-DOPA to dopamine outside of neuronal cells. This greatly lessens the side effects caused by dopamine on the periphery, as well as increasing the concentration of L-DOPA and subsequently dopamine in the brain.
== Disease ==
Parkinson's disease (PD) is a chronic, progressive neurological disease whose symptoms include bradykinesia, tremors, postural instability and rigidity. Although the exact cause of the disease is currently unknown, it is believe to be caused by the apoptosis of dopanergic cells in the substantia nigra of the brain and subsequent loss of dopamine.<ref name="five">PMID:10746727</ref>
== Relevance ==

</StructureSection>
== References ==
<references/>

File:800px-Carbidopa ball-and-stick.png

2016-11-16T02:28:47Z

Andrew Warzinski:

File:512px-Carbidopa.svg.png

2016-11-15T20:34:09Z

Andrew Warzinski: 2D Structure of Carbidopa

2D Structure of Carbidopa

Carbidopa

2016-11-15T20:27:07Z

Andrew Warzinski:

Carbidopa

2016-11-15T05:56:20Z

Andrew Warzinski:

== Carbidopa ==
<StructureSection load='1js3' size='340' side='right' caption='Crystal structure of DOPA Decarboxylase in complex with the inhibitor carbidopa PDB:[[1js3]]' scene=''>
<scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>

== Function ==
<scene name='pdbligand=142:CARBIDOPA'>Carbidopa</scene> inhibits aromatic-L-amino-acid decarboxylase ([[DOPA Decarboxylase]] or DDC)<ref name="one">PMID:11106255</ref> by binding to the <scene name='74/746001/Active_site_dopa/4'>active site</scene>
== Disease ==

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Carbidopa

2016-11-15T05:51:23Z

Andrew Warzinski:

== Carbidopa ==
<StructureSection load='1js3' size='340' side='right' caption='Crystal structure of DOPA Decarboxylase in complex with the inhibitor carbidopa PDB:[[1js3]]' scene=''>
<scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><scene name='74/746001/Active_site_dopa/4'>Active Site</scene>

== Function ==
<scene name='pdbligand=142:CARBIDOPA'>Carbidopa</scene> inhibits aromatic-L-amino-acid decarboxylase (DOPA Decarboxylase or DDC)<ref name="one">PMID:11106255</ref>
== Disease ==

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Carbidopa

2016-11-15T05:48:14Z

Andrew Warzinski:

== Carbidopa ==
<StructureSection load='1js3' size='340' side='right' caption='Crystal structure of DOPA Decarboxylase in complex with the inhibitor carbidopa' scene=''>
<scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><scene name='74/746001/Active_site_dopa/4'>Active Site</scene>

== Function ==
<scene name='pdbligand=142:CARBIDOPA'>Carbidopa</scene> inhibits aromatic-L-amino-acid decarboxylase (DOPA Decarboxylase or DDC)<ref name="one">PMID:11106255</ref>
== Disease ==

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Abbott sandbox

2016-11-15T05:08:30Z

Andrew Warzinski:

==This is a placeholder==
This is a<ref> placeholder<ref/> text to help you get started in
placing a Jmol applet on your page. At any time, click
"Show Preview" at the bottom of this page to see how it goes.

Replace the PDB id (use lowercase!) after the STRUCTURE_ and after PDB= to load
and display another structure.

==Function==
Catalyzes the deacetylation of N-acetylaspartic acid (NAA) to produce acetate and L-aspartate. NAA occurs in high concentration in brain and its hydrolysis NAA plays a significant part in the maintenance of intact white matter.<ref name="UniProt">{{cite web |url=http://www.uniprot.org/uniprot/Q9R1T5#section_comments |title="Aspartoacylase - Rattus norvegicus (Rat)" |date=2010-11-30 |accessdate=2010-12-2}}</ref>

==Reference==
<references />

{{STRUCTURE_3cin | PDB=3cin | SCENE= }}

Carbidopa

2016-11-14T21:31:58Z

Andrew Warzinski:

== Carbidopa ==
<StructureSection load='1js3' size='340' side='right' caption='Caption for this structure' scene=''>
<scene name='pdbligand=142:CARBIDOPA'>Carbidopa</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><scene name='74/746001/Active_site_dopa/4'>Active Site</scene>
This is a default text for your page '''Carbidopa'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Carbidopa

2016-11-14T21:25:47Z

Andrew Warzinski:

== Carbidopa ==
<StructureSection load='1js3' size='340' side='right' caption='Caption for this structure' scene=''>
<scene name='pdbligand=142:CARBIDOPA'>Carbidopa</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><scene name='74/746001/Active_site_dopa/4'>Text To Be Displayed</scene>
This is a default text for your page '''Carbidopa'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Carbidopa

2016-11-14T21:05:15Z

Andrew Warzinski:

== Carbidopa ==
<StructureSection load='1js3' size='340' side='right' caption='Caption for this structure' scene=''>
<scene name='pdbligand=142:CARBIDOPA'>Carbidopa</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><scene name='74/746001/Active_site_dopa/3'>Text To Be Displayed</scene>
This is a default text for your page '''Carbidopa'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Carbidopa

2016-11-14T20:54:32Z

Andrew Warzinski:

== Carbidopa ==
<StructureSection load='1js3' size='340' side='right' caption='Caption for this structure' scene=''>
<scene name='pdbligand=142:CARBIDOPA'>Carbidopa</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><scene name='74/746001/Active_site_dopa/2'>Active Site of Dopa Decarboxylase</scene>
This is a default text for your page '''Carbidopa'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Carbidopa

2016-11-13T23:21:47Z

Andrew Warzinski:

== Carbidopa ==
<StructureSection load='1js3' size='340' side='right' caption='Caption for this structure' scene=''>
<scene name='pdbligand=142:CARBIDOPA'>Carbidopa</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><scene name='74/746001/Active_site_dopa/1'>Active Site of Dopa Decarboxylase</scene>
This is a default text for your page '''Carbidopa'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Carbidopa

2016-11-13T22:59:26Z

Andrew Warzinski:

== Carbidopa ==
<StructureSection load='1js3' size='340' side='right' caption='Caption for this structure' scene=''>
<scene name='pdbligand=142:CARBIDOPA'>Carbidopa</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
This is a default text for your page '''Carbidopa'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Carbidopa

2016-11-13T22:39:16Z

Andrew Warzinski:

==Carbidopa== 0
<StructureSection load='1js3' size='340' side='right' caption='Caption for this structure' scene=''>
<scene name='pdbligand=142:CARBIDOPA'>Carbidopa</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
This is a default text for your page '''Carbidopa'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Carbidopa

2016-11-13T21:25:45Z

Andrew Warzinski: New page: ==Carbidopa== 0 <StructureSection load='1js3' size='340' side='right' caption='Caption for this structure' scene=''> This is a default text for your page '''Carbidopa'''. Click above on ''...

==Carbidopa== 0
<StructureSection load='1js3' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page '''Carbidopa'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>