Carbidopa - Revision history

Andrew Warzinski at 00:39, 6 December 2016

Andrew Warzinski — Tue, 06 Dec 2016 00:39:02 GMT

←Older revision		Revision as of 00:39, 6 December 2016
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	== Structure ==		== 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>	+	[[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 C<sub>10</sub>H<sub>14</sub>N<sub>2</sub>O<sub>4</sub>•H<sub>2</sub>O 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 ==		== 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 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. 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.	+	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==		==Interactions==

Victoria Markunas at 17:05, 3 December 2016

Victoria Markunas — Sat, 03 Dec 2016 17:05:23 GMT

←Older revision		Revision as of 17:05, 3 December 2016
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	== Molecular Mechanism ==		== 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 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.	+	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 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. 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==		==Interactions==
	[[Image:Levodopa.png\|thumb\|left\|2D Structure of Levodopa]][[Image:Dopamine.svg.png\|thumb\|left\|2D Structure of Dopamine]]		[[Image:Levodopa.png\|thumb\|left\|2D Structure of Levodopa]][[Image:Dopamine.svg.png\|thumb\|left\|2D Structure of Dopamine]]
-	Carbidopa ~~only has interactions~~ with Levodopa (L-DOPA) ~~and dopamine, but there are more interactions between Levodopa~~ 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 ~~only interaction is~~ to reduce side effects of ~~Levodopa~~ 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.	+	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 ==		== 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 mostly ~~related to~~ people with Parkinson’s disease. 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>	+	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>		</StructureSection>
	== References ==		== References ==
	<references/>		<references/>

Victoria Markunas at 16:42, 3 December 2016

Victoria Markunas — Sat, 03 Dec 2016 16:42:07 GMT

←Older revision		Revision as of 16:42, 3 December 2016
Line 1:		Line 1:
	==Carbidoba ((2S)-3-(3,4-dihydroxyphenyl)-2-hydrazinyl-2-methylpropanoic acid)==		==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]])'>	+	<StructureSection load='1js3' size='340' side='right' caption='Crystal structure of DOPA Decarboxylase in complex with the inhibitor carbidopa (PDB Code [[1js3]])'>

	== Function ==		== Function ==

Victoria Markunas at 03:45, 17 November 2016

Victoria Markunas — Thu, 17 Nov 2016 03:45:43 GMT

←Older revision		Revision as of 03:45, 17 November 2016
Line 9:		Line 9:

	== Molecular Mechanism ==		== 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.	+	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 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.

	==Interactions==		==Interactions==

Victoria Markunas at 03:32, 17 November 2016

Victoria Markunas — Thu, 17 Nov 2016 03:32:44 GMT

←Older revision		Revision as of 03:32, 17 November 2016
Line 1:		Line 1:
	==Carbidoba ((2S)-3-(3,4-dihydroxyphenyl)-2-hydrazinyl-2-methylpropanoic acid)==		==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]])~~' scene='~~'>	+	<StructureSection load='1js3'size='340' side='right' caption='Crystal structure of DOPA Decarboxylase in complex with the inhibitor carbidopa (PDB Code [[1js3]])'>
		+
	== Function ==		== 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>		<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>

Victoria Markunas at 03:16, 17 November 2016

Victoria Markunas — Thu, 17 Nov 2016 03:16:50 GMT

←Older revision		Revision as of 03:16, 17 November 2016
Line 12:		Line 12:
	==Interactions==		==Interactions==
	[[Image:Levodopa.png\|thumb\|left\|2D Structure of Levodopa]][[Image:Dopamine.svg.png\|thumb\|left\|2D Structure of Dopamine]]		[[Image:Levodopa.png\|thumb\|left\|2D Structure of Levodopa]][[Image:Dopamine.svg.png\|thumb\|left\|2D Structure of Dopamine]]
-	Carbidopa only interactions ~~include~~ dopamine and Levodopa. Carbidopa works by inhibiting the enzyme activity of DDC, when both are working in the ~~system~~ it blocks the Levodopa negative side effects ~~Levodopa is~~ lipid soluble ~~so it~~ can pass the blood-brain barrier where Carbidopa cannot.	+	Carbidopa only has interactions with Levodopa (L-DOPA) and dopamine, but there are more interactions between Levodopa 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 only interaction is to reduce side effects of Levodopa 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 ==		== 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>Carbidopa is mostly related to people with Parkinson’s disease. 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="~~eight~~">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, ~~about~~ 80%. ~~Current~~ treatments for Parkinson’s disease ~~are~~ combined tablet of Carbidopa and Levodopa (Sinemet)~~, which~~ are offered as immediate-release tablets and slow-release tablets, along with dissolvable tablets.<ref name="~~nine~~">http://www.merck.com/product/home.html</ref>	+	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 mostly related to people with Parkinson’s disease. 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>
-		+
-	~~<ref name="ten">PMID:18828673</ref>~~	+
-	~~<ref name="eleven">PMID:10939456</ref>~~	+
-	~~<ref name="twelve">PMID:22131937</ref>~~	+
-		+

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

Victoria Markunas at 02:15, 17 November 2016

Victoria Markunas — Thu, 17 Nov 2016 02:15:36 GMT

←Older revision		Revision as of 02:15, 17 November 2016
Line 18:		Line 18:

	<ref name="ten">PMID:18828673</ref>		<ref name="ten">PMID:18828673</ref>
		+	<ref name="eleven">PMID:10939456</ref>
		+	<ref name="twelve">PMID:22131937</ref>

Victoria Markunas at 20:39, 16 November 2016

Victoria Markunas — Wed, 16 Nov 2016 20:39:59 GMT

←Older revision		Revision as of 20:39, 16 November 2016
Line 2:		Line 2:
	<StructureSection load='1js3'=size='340' side='right' caption='Crystal structure of DOPA Decarboxylase in complex with the inhibitor carbidopa (PDB Code:[[1js3]])' scene=''>		<StructureSection load='1js3'=size='340' side='right' caption='Crystal structure of DOPA Decarboxylase in complex with the inhibitor carbidopa (PDB Code:[[1js3]])' scene=''>
	== Function ==		== 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>.	+	<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 ==		== Structure ==

Victoria Markunas at 20:37, 16 November 2016

Victoria Markunas — Wed, 16 Nov 2016 20:37:28 GMT

←Older revision		Revision as of 20:37, 16 November 2016
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	== Structure ==		== 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>	+	[[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 ==		== Molecular Mechanism ==

Victoria Markunas at 20:00, 16 November 2016

Victoria Markunas — Wed, 16 Nov 2016 20:00:19 GMT

←Older revision		Revision as of 20:00, 16 November 2016
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	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>Carbidopa is mostly related to people with Parkinson’s disease. 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="eight">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, about 80%. Current treatments for Parkinson’s disease are combined tablet of Carbidopa and Levodopa (Sinemet), which are offered as immediate-release tablets and slow-release tablets, along with dissolvable tablets.<ref name="nine">http://www.merck.com/product/home.html</ref>		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>Carbidopa is mostly related to people with Parkinson’s disease. 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="eight">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, about 80%. Current treatments for Parkinson’s disease are combined tablet of Carbidopa and Levodopa (Sinemet), which are offered as immediate-release tablets and slow-release tablets, along with dissolvable tablets.<ref name="nine">http://www.merck.com/product/home.html</ref>

-	<ref name="~~eleven~~">PMID:18828673</ref>	+	<ref name="ten">PMID:18828673</ref>