The Secret Life of Levodopa
62.4 هزار بار بازدید -
7 سال پیش
-
References:Biosynthetic Incorporation of Oxidised Amino
References:
Biosynthetic Incorporation of Oxidised Amino Acids into Proteins and their Cellular Proteolysis. Rodgers K.J., Wang, HJ and Dean, RT. Free Radical Biology and Medicine, 32(8), 766-775, 2002
Biosynthesis and Turnover of DOPA-containing Proteins by Human Cells
Rodgers K.J. Hume P.M. Dunlop, R.A. and Dean, RT Free Radical Biology and Medicine, 37(11), 1756-1764, 2004
Translational Incorporation of L-3,4-Dihydroxyphenylalanine (DOPA) into Proteins
Kiyoshi Ozawa, Madeleine J. Headlam, Dmitri Mouradov, Jennifer L. Beck, Kenneth J. Rodgers, Roger T. Dean, Thomas Huber, Gottfried Otting and Nicholas E. Dixon
FEBS J. 272 (12): 3162-3171, 2005
Evidence for L-dopa incorporation into cell proteins in patients treated with levodopa
Kenneth J. Rodgers, Peter M. Hume, John G. Morris and Roger T. Dean
Journal of Neurochemistry, 98, 1061-1067, 2006
Misincorporation of Amino Acid Analogues into Proteins by Biosynthesis.
Kenneth J. Rodgers and Nae Shiozawa
The International Journal of Biochemistry and Cell Biology, 40 (8), 1452-1466, 2008
L-DOPA is incorporated into brain proteins of patients treated for Parkinson’s disease, inducing toxicity in human neuroblastoma cells in vitro.
Sandra W. Chan, Rachael A. Dunlop, Anthony Rowe, Kay L. Double and Kenneth J. Rodgers
Experimental Neurology 2012, 238(1): 29-37
_______________________________________________________________________________________________________________
This animation shows the insidious nature of Levodopa.
Ribosome Studio is an animation studio based in Switzerland. We produce high-quality scientific animations, medical animations and mechanism of action movies. For more information go to http://www.ribosomestudio.com
_______________________________________________________________________________________________________________
Transcript:
Levodopa is a therapeutic drug that is used to treat the symptoms of Parkinson’s disease.
In the brain, this molecule is converted to the biochemically active dopamine by enzymatic decarboxylation. Dopamine is then used as a neurotransmitter to stimulate muscular movement.
With its amine and carboxyl functional groups; Levodopa is also an amino acid but one that is not used in protein synthesis, sometimes called a non-protein amino acid . It is structurally very similar to Tyrosine and only differs by a single hydroxyl group.
Levodopa enters the brain through an amino acid transporter.
Levodopa is then taken up by specific neurones in the brain called dopaminergic neurones. These specialized cells contain the enzyme AADC that converts DOPA to the neurotransmitter dopamine.
However, in the neuron or any other cell, the similarity of levodopa to Tyrosine allows it to be mistakenly used to synthesize new proteins.
This incorporation causes a change in the protein structure and in some cases the protein is no longer able to perform the correct role. It can even cause the protein to lose solubility
In some cases these abnormal proteins can then be broken down and levodopa returned to the pool of amino acids to be used again.
But some of the misfolded proteins are not degraded efficiently and begin to aggregate inside the cell.
Some of these aggregates become resistant to being broken down and become insoluble plaques or tangles.
This process can occur over many years or even decades.
Eventually, the buildup of these aggregates combined with other stress factors can cause the neurones to undergo apoptosis; a type of cell suicide.
Levodopa and Levodopa containing proteins can then be released into the surrounding environment where they can enter other cells leading to progressive neuronal death over time.
This could have a negative impact on the sufferers brain function.
Biosynthetic Incorporation of Oxidised Amino Acids into Proteins and their Cellular Proteolysis. Rodgers K.J., Wang, HJ and Dean, RT. Free Radical Biology and Medicine, 32(8), 766-775, 2002
Biosynthesis and Turnover of DOPA-containing Proteins by Human Cells
Rodgers K.J. Hume P.M. Dunlop, R.A. and Dean, RT Free Radical Biology and Medicine, 37(11), 1756-1764, 2004
Translational Incorporation of L-3,4-Dihydroxyphenylalanine (DOPA) into Proteins
Kiyoshi Ozawa, Madeleine J. Headlam, Dmitri Mouradov, Jennifer L. Beck, Kenneth J. Rodgers, Roger T. Dean, Thomas Huber, Gottfried Otting and Nicholas E. Dixon
FEBS J. 272 (12): 3162-3171, 2005
Evidence for L-dopa incorporation into cell proteins in patients treated with levodopa
Kenneth J. Rodgers, Peter M. Hume, John G. Morris and Roger T. Dean
Journal of Neurochemistry, 98, 1061-1067, 2006
Misincorporation of Amino Acid Analogues into Proteins by Biosynthesis.
Kenneth J. Rodgers and Nae Shiozawa
The International Journal of Biochemistry and Cell Biology, 40 (8), 1452-1466, 2008
L-DOPA is incorporated into brain proteins of patients treated for Parkinson’s disease, inducing toxicity in human neuroblastoma cells in vitro.
Sandra W. Chan, Rachael A. Dunlop, Anthony Rowe, Kay L. Double and Kenneth J. Rodgers
Experimental Neurology 2012, 238(1): 29-37
_______________________________________________________________________________________________________________
This animation shows the insidious nature of Levodopa.
Ribosome Studio is an animation studio based in Switzerland. We produce high-quality scientific animations, medical animations and mechanism of action movies. For more information go to http://www.ribosomestudio.com
_______________________________________________________________________________________________________________
Transcript:
Levodopa is a therapeutic drug that is used to treat the symptoms of Parkinson’s disease.
In the brain, this molecule is converted to the biochemically active dopamine by enzymatic decarboxylation. Dopamine is then used as a neurotransmitter to stimulate muscular movement.
With its amine and carboxyl functional groups; Levodopa is also an amino acid but one that is not used in protein synthesis, sometimes called a non-protein amino acid . It is structurally very similar to Tyrosine and only differs by a single hydroxyl group.
Levodopa enters the brain through an amino acid transporter.
Levodopa is then taken up by specific neurones in the brain called dopaminergic neurones. These specialized cells contain the enzyme AADC that converts DOPA to the neurotransmitter dopamine.
However, in the neuron or any other cell, the similarity of levodopa to Tyrosine allows it to be mistakenly used to synthesize new proteins.
This incorporation causes a change in the protein structure and in some cases the protein is no longer able to perform the correct role. It can even cause the protein to lose solubility
In some cases these abnormal proteins can then be broken down and levodopa returned to the pool of amino acids to be used again.
But some of the misfolded proteins are not degraded efficiently and begin to aggregate inside the cell.
Some of these aggregates become resistant to being broken down and become insoluble plaques or tangles.
This process can occur over many years or even decades.
Eventually, the buildup of these aggregates combined with other stress factors can cause the neurones to undergo apoptosis; a type of cell suicide.
Levodopa and Levodopa containing proteins can then be released into the surrounding environment where they can enter other cells leading to progressive neuronal death over time.
This could have a negative impact on the sufferers brain function.
7 سال پیش
در تاریخ 1396/05/04 منتشر شده
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