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Hi ladies um this is my presentation on carbidopa um the use of x-ray crystallography and as well as using the program chimera to show you where the cardopa or carbidopa um bonds within the molecule so in order to understand what carbidopa is we need to understand what it treats um basically what it is is parkinson’s disease which is a progressive nervous system

Disorder that manifests itself as movement issues so the neurons in the brain gradually break down or die these neurons produce the chemical message or dopamine and when these levels decrease it causes the um abnormal brain activity leading to impaired movement so for example you’ll see patients with parkinson’s that kind of shuffle their feet when they walk um

They don’t swing their arms back and forth so you’ll see brady brady kinesia which is the slowing of everything they talk slow it takes them a really long time to put their shoes on or get dressed or use the restroom etc speech issues such as slurring they’re very monotone so there’s no inflection within their voice and they’re very quiet when they speak um the

Other big telltale sign of parkinson’s is tremor so you notice them shaking a lot um their head will bobble their fingers will move it’s just an all-over progressive movement they’ll have balance and postural issues so um for example my dad has parkinson’s um so not only does he tremor but he also kind of hunches over when he walks he falls very easily so his

Balance is not where it should be and then eventually you end up with the loss of automatic movement such as blinking facial expressions eating becomes an issue swallowing becomes an issue and that seems to be in more of the advanced state so essentially there’s no cure at this point but these medications that we’ll talk about will significantly improve symptoms

If taken so carbidopa is what we were asked to talk about it’s also known as under the trade name is ledocin it’s used to treat the symptoms of parkinson’s disease specifically the tremors and the rigidity of the muscles it can also be used to treat parkinson type symptoms which is caused by the side effects of certain medications poisonous gases as well as some

Minerals that become ingested it’s commonly used in conjunction with levodopa which is um the other parkinson medication that we’re going to talk about to kind of bring all of this together for better understanding um carbidopa is also an aromatic l amino acid carboxylase inhibitor um so this is an enzyme um it inhibits this enzyme so this is the structure

Of carbidopa so carbidopa and levodopa kind of work in conjunction um the levodopa works within the central nervous system by converting um a system by being converted into the dopamine once it reaches the blood brain barrier um so levodopa levodopa is the the precursor for dopamine which is converted into dopamine by the l dopa decarboxylase or dcc or ddc for

Short so basically the ddc is the activation that leads to the production of the dopamine and the serotonin that your body needs for movement just um yeah for movement carbidopa works by preventing this levodopa from being broken down before it reaches the blood-brain barrier so in conjunction the carbidopa helps the levodopa to get into the brain so it can be

Broken down to make the dopamine that is necessary for the neurons to be sharing um the messages between your nerve cells in order for the movement to work um so dopamine like it says is a neurotransmitter that your nervous system uses to send messages between nerve cells and so basically what happens in parkinson’s is the dopamine um dies or fails to be made

And then the messages between nerve signals ends up not being relayed which ends up with the rigidity the tremors the postural balance issues that we talked about cardopa carbodopa can be administered both orally inhaled or infused depending upon um basically where you uh the patient is within their disease process so this is just a quick little schematic um so

Essentially the levodopa is what is necessary to make more of the dopamine in the patient’s brain so that the neurotransmitter can work but cardopa is given in addition to it so it breaks down this dcc so the dopamine isn’t made outside of the blood brain barrier which is this right here so once levodopa levodopa gets through this blood-brain barrier you can kind

Of follow and see what happens then it the dopamine then snaps is out and does what it needs to do for the neurotransmitter because here’s the other nerve so that’s a little bit about that process the next thing we needed to talk about was x-ray crystallography um and so we kind of talked about this already in our discussion but x-ray crystal crystallography

Is used to obtain the three-dimensional structure of a particular protein by sending x-rays through the crystal and so the x-rays go through and it diffracts and then what it does is goes through an electronic detector which kind of shows where um the x-rays are being diffracted from out of the crystal the crystal is then rotated by a computer which is used

To obtain specific orientation set forth by the researcher so basically the researcher will put in like coordinates um kind of like a gps system i guess and it kind of tells the computer how to rotate the crystal in order to get the necessary information and then the intensity of each of these diffracted rays is entered into the computer where then a series of

Math calculations are done from all of the positions of the sample and it kind of will project what will project you a 3d image which we’ll see in the next slide and this is measured the distance is measured within um x-ray crystallography is measured between atoms and egg strums so this is kind of um a very dumbed down version i guess of how it works um

The sample needs to be in a crystallized form then the x-rays are shot through this crystal which makes this diffraction pattern these diffraction points are then made into an electron density map and then this spits out your final 3d structure of your protein now this cardopa chimera thing um i’m a little not 100 positive about so um bear with me but um so

By putting in carbidopa into our chimera program i kind of took away some of the side views so you could see more internally the purple right here is the carbidopa and it’s binding right here to this green outlined molecule and this is called plp and so the cardopa binds to the ddc by a hydro zone linkage with plp and so this is kind of where it all bonds

Together so i don’t know i hope that answered the question i wasn’t completely 100 positive but um you can kind of see where the cardopa then binds and this is the inhibitor so then this inhibitor will or the um the inhibitor stops the breakdown of um the levodopa before it hits the brain very the blood-brain barrier so i hope i didn’t confuse you more if

You’ve got questions let me know hope this was helpful thanks

Transcribed from video
Carbidopa By Erica Henry