Understanding Peroxisomes and Their Disorders

all right ninja nerds in this video today we're going to be talking about peroxisomes and paroxysmal disorders

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account go check all those out all right engineers let's get into it all right ninja so we're going to start

talking about the function of peroxisomes we talked a little bit about them in the

structure and function of the cell video but we're going to kind of elaborate on those

functions a little bit more so one really big function of the peroxisomes is that they play a role in fatty acid

metabolism you know there's particular types of fatty acids what's called very long chain fatty

acids so very long chain fatty acids very long chain fatty acids and then there's other ones which are

called branched chain fatty acids so branch chain fatty acids these molecules okay are brought into

peroxisomes they're very special transporters and these transported these blue proteins

here they're called abcd1 transporters so a b c d

one transporters and these are very important because we need these in order to get these fatty acids

into the peroxisome now once these fatty acids are brought into the peroxisome what happens to them

well let's focus on the very long chain fatty acids first once you bring these very long chain

fatty acids into this peroxisome it undergoes a process called beta oxidation if you guys have watched our

biochemistry videos you guys remember what that's called and what happens there

we take the fatty acid and through a series of four steps you guys can remember that via the

mnemonic oh hot and that was oxidation hydration so you're adding in water

another oxidation step and then one more step which is called a thiolase activity or thialation

these are the ac the actual steps within the beta oxidation pathway so what is this

pathway called this is the beta oxidation pathway very important and then what happens is

as the at the end result of this beta oxidation pathway you generate acetyl coas

okay and these acetyl-coa molecules can be just kind of like remember you're taking these fatty acids

and chopping off two carbons at a time so the remaining amounts you're actually going to get two molecules out of this

you'll get acetyl coa but the other molecules that you get out of this is called acyl

coas which are just basically the remaining of the very long chain fatty acids after

they've been broken down the acyl coas can just go back up to this step and then re-go through it

again so it's just a consistent process a consistent cycle if you will

now this process is very important within the peroxisomes and one of the reasons why is in the actual proc

during this process this beta oxidation you generate a particular molecule from the oxidation

step you generate a molecule called hydrogen peroxide

and that's very interesting so the more very long-chain fatty acids that get beta-oxidized into acetyl coa and acyl

coas the more hydrogen peroxide you generate that's the first step i want you to

remember so the first function is beta oxidation within the proxosomes

the second function is you bring these next ones in these branched chain fatty acids and branched

chain fatty acids can get converted into very long chain fatty acids so you're

just basically cutting off these little branches and then they are very long chain fatty

acids that undergo bait oxidation and do the same process but this step here where you go

from branch chain fatty acids to very long chain fatty acids is called alpha

oxidation so very important there all right so two things that we've already seen within the peroxisomes

one is the beta oxidation of very long chain fatty acids and the second one is alpha oxidation of

branched chain fatty acids ba-boom all right you know another function of the peroxisomes there's

another really interesting one you can thank your peroxisomes for this you know when you're getting a little

bit of red wine in you you know a little bit of loudmouth soup in you there's a little molecule within that

called ethanol and ethanol is actually metabolized by you know they can be metabolized in your

smooth endoplasmic reticulum but also within your peroxisomes so ethanol can get taken into these peroxisomes

and when they're taken into the peroxisomes they actually get broken down

right into a particular molecule here called acetaldehyde acetaldehyde

alda hyde and that's important and the reason why is in this actual peroxisome remember this

molecule this h2o2 molecule well we can actually use some of this hydrogen peroxide molecules

in this step and through that we generate water and we generate oxygen right and in this step here it's just

the opposite so whenever you're utilizing very long chain fatty acids to make acetyl-coa

molecules and acyl coas guess what you're putting into the reaction water and oxygen

and as a result you're generating hydrogen peroxide same thing in this ethanol metabolism

when you break down ethanol to acetaldehyde you utilize hydrogen peroxide and

generate water and oxygen this would be the third function of the peroxisomes

is ethanol metabolism the fourth function of the actual peroxisomes is you have bile acids but

these bile acids they're not activated okay so we're going to call these bile acid intermediates

what happens is these bile acid intermediates have to get taken up into the peroxisome

and through these particular enzymes present within the peroxisomes they help to

activate these bile acids so then you get activated bile acids and these activated bile

acids can then be released from the peroxisomes and then go out to like the smooth endoplasmic

reticulum so this is going to be the fourth function of what the peroxisomes which

is bile acid activation and metabolism all right the next function the fifth function you know whenever you take

these acetyl-coa molecules with that comes from this beta-oxidation process

you know what you can do with these you can take these acetyl-coa molecules combine them with multiple acetyl-coa

molecules and synthesize cholesterol now cholesterol is not completely

synthesized in the actual peroxisomes they actually are made a good chunk of cholesterol is

actually made up a particular intermediate of cholesterol is made in the peroxisomes

and then it gets sent to the smooth endoplasmic reticulum which completely leads to the formation of cholesterol

but again big thing to take away from this is that peroxisomes help in aiding in the synthesis of

cholesterol so this would be the fifth function is cholesterol synthesis

now what is the significance of cholesterol we can use this in our cell membrane

right it's very important for kind of maintaining fluidity in the cell membrane especially with temperature

changes and it's important for steroid hormones it's important for steroid hormones such

as testosterone estrogen all of these different molecules you know what else that's important for

making bile acids so again really important thing to remember here is that the peroxisomes help

in the formation of cholesterol they don't completely make it in the peroxisomes

they lead to the formation of particular intermediates that then get shipped to the smooth er

which help to finish that up and make the cholesterol and again the cholesterol is important for cell

membrane component steroid hormones and bile acids that's the fifth function the sixth function is

a very interesting one you know these acl coas they're just basically fatty acids

okay so essentially we can just kind of call these like fatty acids they're just kind of like remaining

pieces of these very long chain fatty acids after they underwent bait oxidation these fatty

acids you can combine them with a particular molecule that your actual

peroxisomes can take up you know there's a molecule called glycerol and glycerol eventually gets converted

into a molecule called phosphate i know you guys remember that from glycolysis right so once

dihydroxyacetone phosphate combines with some of these fatty acids guess what it makes

it makes a particular type of phospholipid you know what phospholipid this is this

is called plasmalogen plasmalogen is very important you want to know why

because it's incorporated into myelin what is myelin important for it's important for forming the actual

myelin sheaths within nerves of your central nervous system and peripheral nervous system

so that is very important when it comes to the components of the central nervous

system and peripheral nervous system particularly myelinating the axons there so

this would be which function this would be the sixth function is plasmalogen synthesis which

is important for myelin and neurons the last function and probably one of the more interesting

functions here is the relationship with free radicals so you've already noticed one free

radical that's kind of getting produced a lot especially with this fatty acid oxidation you're producing a lot of

these hydrogen peroxides and also you know from your electron transport gene your electron transport

chain also generates a lot of free radicals and if you guys remember your kind of free radical reactions here

like you can take for example oxygen and then from certain types of processes you get converted into

a superoxide anion that superoxide can get converted into hydrogen peroxide and then hydrogen

peroxide can get converted into a hydroxyl free radical why is this important because these molecules right

here superoxide hydrogen peroxide and hydroxyl free radical hydroxyl molecule

are free radicals you know why free radicals are damaged damaging and dangerous

these molecules here can bind onto dna they can bind onto proteins and they can bind onto lipids

and then they're going to damage the dna damage the proteins and damage these lipids and you know what these are

important for our cell membrane or organelles and if these get damaged it really causes a lot

of cellular dysfunction so thankfully and beautifully our actual what our peroxisomes has a beautiful

enzyme that takes this hydrogen peroxide and converts it into

water and oxygen what is this molecule that we should be so thankful for

this molecule is called catalase so this is called catalase so all of this hydrogen peroxide is being built up

within the cell from what processes from the beta oxidation pathway and coming from

electron transport chain remember that this hydrogen products will get converted into water and oxygen

which is going to prevent the buildup of hydrogen peroxide which leads to free radical damage so again what is the

seventh and final function the seventh and final function is this catalyst activity which reduces

hydrogen peroxide buildup and therefore free radical damage all right ninja so now that we

understand the function of peroxisomes this this is really going to be helpful to

understand these paroxysmal disorders now you might be like why the heck do i need to know this this is very

very important for your usmle step one exams so it's very important that you truly

understand peroxisomal function because it'll help you to understand the peroxisomal disorders

there's a particular condition called zellweger syndrome in zellweger syndrome the first thing that you need to know

that's very important is that it is autosomal recessive it is autosomal recessive so you need

two kind of mutant alleles basically uh particularly for a specific

gene and that gene is called the pex gene and whenever you have this autorecessive

disorder you don't express the pex gene why is that important because the pex gene

codes for particular proteins called peroxins that are essential to making peroxisomes

so if you don't make pect if you don't express pex genes you don't make proteins that lead to the

formation of peroxism so there's a decrease in peroxisomes so now all we got to

remember is everything that the peroxisomes did what did they do

they broke down fatty acids if they can't break them down because they're not there what happens you accumulate

an increase in very long chain fatty acids you increase the accumulation of

branched chain fatty acids what else it broke down ethanol well you can't break down ethanol

so now you're going to have an accumulation of ethanol then what else you aren't able to break

down hydrogen peroxide into water so you accumulate hydrogen peroxide

and also if you don't if you forget that you won't be able to synthesize cholesterol

plasma allergen all of those good things so if that's the case then guess what

happens this hydrogen peroxide very long chain fatty acids branch chain fatty acids ethanol

all accumulate within particular tissues and cause damage and affliction to these tissues

you can remember this by neuro neurohepatorenal syndrome when it ends up kind of accumulating

within the tissues in the central nervous system this leads to neurodegeneration that

presents with hypotonia which is kind of like really floppy uh kind of muscles

and this is very common in babies it causes like a floppy baby syndrome and also it can lead to seizures okay so

this is another important thing when it accumulates in the liver it causes the actual liver to not be able

to process bilirubin as well so bilirubin a pigment in the blood actually accumulates and

leads to jaundice because that bilirubin starts depositing in the skin

and in the eyes the sclera particularly it also can affect the way that the actual

kidneys the tubules are developing within the actual urinary system and this can lead to

polycystic kidney disease very important very high yield to know this condition

all right the next condition is called rafsson's disease refshames disease is also an autosomal

recessive disorder and it leads to decreased expression or loss of expression

for genes involved in alpha oxidation remember that alpha oxidation pathway

what happened in the alpha oxidation pathway you took a molecule called a branched chain fatty acid and

through the process of alpha oxidation we'll just put there is alpha ox you break that branch chain fatty acid into

what kind of molecule a very long chain fatty acid okay and if you don't do that then these

branched chain fatty acids will build up within the actual tissues what tissues will it build up in it'll

build up within the the central nervous system and the peripheral nervous system the skin

and within the epiphyseal plates what will that lead to if it accumulates within the central

nervous system this really loves to damage the cerebellum this leads to ataxia

it loves to damage the actual nerves you know you have the actual peripheral nerves that come out here

it loves to damage these and this leads to neuropathy and you know what else it also loves to

damage the retina so particularly it accumulates within the retina and when it accumulates in

the retina it leads to a condition called retinitis pigmentosa and that causes like particularly like

night blindness and visual changes and it can even cause cataracts but these are the three big ones

it also accumulates within the skin tissue and leads to ichthyosis

okay it also accumulates within the epiphyseal plates and affects the actual growth of the epiphyseal blades and

causes dysplasia of the epiphyseal plates so we call this epiphyseal

dysplasia but you know what's actually really interesting about this the you know your exams love to give you

a classical kind of like buzzword term and this causes whenever you have dysplasia of the epiphyseal

plates the toe the forced toe doesn't actually grow correctly

and so because of that this causes shortening of the fourth toe very important thing

there so that covers rafsam's disease all right this next condition is called adrenal leukodystrophy this is an

x-linked recessive an x-linked recessive disorder and what happens is because it's

x-linked it's going to be more common in which type of sex males are females males so because of

that remember that this will have more of a predominance within males the next thing

is that if this is excellent recessive it leads to the loss of expression of a

particular type of gene called well the abcd1 gene and that gene basically encodes for that

protein the abcd1 protein remember that protein the abcd1 protein brings in the very

long chain fatty acids and the branched chain fatty acids it brings it into the peroxisome so that they can be

metabolized well if these aren't brought in what happens they're not able to get

metabolized and because of that these very long chain fatty acids and branched chain

fatty acids start to accumulate within sight of the tissues what tissues it accumulates within the central

nervous system and peripheral nervous system in the adrenal cortex when it accumulates here it really loves

to cause damage to your actual central nervous system and it commonly leads to dementia

okay and progressive neurodegeneration the other thing that's very interesting is it loves to accumulate within the

adrenal cortex and when it accumulates within the adrenal cortex do you guys remember the

hormones that are made by your adrenal cortex the two big ones by the zona glomerulos

and the zone of fasciculata that is aldosterone that'll have significant decreased

production and cortisol that'll also have significant decreased production

why is this dangerous because in children if this is very very low these levels this can lead

to what's called adrenal crisis which can be very fatal so very very very important thing to

remember here okay so that covers adrenal leukodystrophy and therefore the

peroxisomal disorders all right ninja so in this video we talk about peroxisomes and the associated

peroxisomal disorders i hope it made sense and i hope that you guys did like it all right ninja nerds as always until

next time [Music] you