Metabolism | Cholesterol Metabolism
Summary
TLDRThis video delves into the intricate world of cholesterol metabolism, highlighting its vital role in the synthesis of essential compounds like bile salts, steroid hormones, and cell membrane integrity. It explains the liver's endogenous cholesterol production from acetyl CoA and the significance of enzymes like HMG-CoA reductase, which is targeted by statins to manage high cholesterol levels. The script also touches on cholesterol's multifaceted uses, including its structural contributions to cell membranes and its transformation into various hormones, emphasizing the balance needed to prevent health issues.
Takeaways
- 🧬 Cholesterol metabolism is crucial for various bodily functions, including the production of bile salts, steroid hormones, and as a component of cell membranes.
- 🚀 Cholesterol synthesis primarily occurs in the liver and involves the conversion of acetyl CoA into cholesterol through a series of enzymatic steps.
- 🔬 The rate-limiting step in cholesterol synthesis is catalyzed by the enzyme HMG-CoA reductase, which is highly regulated and targeted by statin drugs like Lipitor to lower cholesterol levels.
- 💊 Statins work by inhibiting HMG-CoA reductase, thus reducing cholesterol synthesis for individuals with high cholesterol.
- 🔄 Cholesterol is also obtained through an exogenous pathway by ingesting food and transported to different tissues via chylomicrons.
- 🌀 Cholesterol plays a significant role in cell membranes, affecting fluidity and preventing drastic phase transitions, as well as being part of lipid rafts for signaling pathways.
- 🚀 Cholesterol is a precursor for the synthesis of various steroid hormones, including testosterone, estrogen, progesterone, and corticosteroids.
- 🧴 Bile salts, synthesized from cholesterol in the liver, are essential for emulsifying fats, making them more soluble and easier to digest.
- 🚛 Lipoproteins are molecules that transport cholesterol and other lipids through the bloodstream to different tissues, including LDL (low-density lipoprotein) and HDL (high-density lipoprotein).
- 🔑 Insulin is an anabolic hormone that stimulates cholesterol synthesis, while glucagon opposes it, promoting the use of cholesterol for energy production or glucose synthesis.
- 🌿 NADPH is required as a reducing agent in the cholesterol synthesis pathway, highlighting its importance in various biosynthetic processes within the body.
Q & A
What is the primary role of cholesterol in the body?
-Cholesterol serves as a basic unit for various functions in the body, including the synthesis of bile salts, steroid hormones such as testosterone, progesterone, estrogen, and cortisol, and as an integral component of cell membranes. It is also involved in the transport of cholesterol via lipoproteins.
Where does cholesterol metabolism mainly occur?
-Cholesterol metabolism primarily occurs in the liver, although cholesterol can be ingested through food and transported to different tissues via chylomicrons.
What is the significance of acetyl CoA in cholesterol synthesis?
-Acetyl CoA is the basic unit used for cholesterol synthesis. It undergoes a series of enzymatic reactions to form cholesterol.
What is the role of insulin in cholesterol metabolism?
-Insulin is the main anabolic hormone in the body and plays a crucial role in cholesterol metabolism by stimulating the enzyme HMG-CoA reductase, which is involved in cholesterol synthesis.
What are bile salts and why are they important?
-Bile salts are molecules derived from cholesterol that aid in the emulsification of large fat globules, making them more soluble in water and easier to digest. They are crucial for the digestion and absorption of dietary fats.
What is the function of HMG-CoA reductase in cholesterol synthesis?
-HMG-CoA reductase is the rate-limiting enzyme in cholesterol synthesis. It catalyzes the conversion of HMG-CoA to mevalonate, which is a crucial step in the production of cholesterol.
How do statins like Lipitor help in managing high cholesterol levels?
-Statins, including Lipitor, inhibit the enzyme HMG-CoA reductase, thus reducing the synthesis of cholesterol in the liver and lowering overall cholesterol levels in the body.
What is the purpose of incorporating cholesterol into cell membranes?
-Cholesterol in cell membranes helps regulate fluidity, making the membrane less fluid and more rigid. It also prevents drastic phase transitions and is involved in the formation of lipid rafts, which are important for cell signaling processes.
What are lipoproteins and how are they related to cholesterol transport?
-Lipoproteins are complexes of lipids and proteins that transport cholesterol and other lipids through the bloodstream to different tissues. Examples include VLDL, LDL, and HDL, each with specific roles in lipid transport and metabolism.
Why is the synthesis of cholesterol regulated?
-The synthesis of cholesterol is highly regulated because excessive cholesterol can lead to health problems such as atherosclerosis. The body controls cholesterol levels through feedback mechanisms involving HMG-CoA reductase and the influence of hormones like insulin and glucagon.
What is the role of NADPH in cholesterol synthesis?
-NADPH acts as a strong reducing agent and is required in the conversion of HMG-CoA to mevalonate during cholesterol synthesis. It provides the necessary reducing power for this reaction to occur.
Outlines
🧬 Cholesterol Metabolism Basics and Importance
This paragraph introduces the concept of cholesterol metabolism, emphasizing its importance due to cholesterol's role as a fundamental component in various biological processes. It mentions bile salts' role in fat emulsification, the synthesis of steroid hormones such as testosterone and cortisol, and the transport of cholesterol via lipoproteins. The paragraph also highlights the liver's role in endogenous cholesterol production from acetyl CoA, a process that will be detailed throughout the video, including the involvement of key enzymes and the regulation by hormones like insulin.
🛠️ Cholesterol Synthesis from Acetyl CoA
The paragraph delves into the biochemical pathway of cholesterol synthesis starting from acetyl CoA. It describes the initial steps where two acetyl CoA molecules are fused to form acetoacetyl CoA, facilitated by the enzyme thiolase. Subsequent reactions lead to the formation of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA), catalyzed by HMG-CoA synthase. The paragraph underscores the significance of HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis and a target for drugs like statins, which are used to lower cholesterol levels in individuals with hypercholesterolemia.
🌱 Cholesterol's Role in Cell Membranes and Beyond
This section discusses cholesterol's structural role in cell membranes, where it contributes to membrane rigidity and prevents phase transitions, as well as its involvement in forming lipid rafts with glycosphingolipids, which are crucial for cellular signaling. The paragraph also outlines the conversion of cholesterol into various steroid hormones, the synthesis of bile salts for lipid emulsification in the small intestine, and the packaging of cholesterol into lipoproteins for transport to different tissues, highlighting the versatility and essential nature of cholesterol in the body.
🔬 Detailed Cholesterol Metabolism and Regulation
The paragraph provides an in-depth look at the cholesterol metabolism process, from the conversion of isopentyl pyrophosphate into squalene, which involves numerous enzymatic steps and the enzyme squalene synthase, to the formation of cholesterol from 7-dehydrocholesterol. It explains how cholesterol is not only a component of cell membranes and a precursor for steroid hormones and bile salts but also a crucial molecule for the synthesis of lipoproteins, which are essential for transporting cholesterol to peripheral tissues. The paragraph also touches on the regulatory mechanisms involving HMG-CoA reductase, insulin, and glucagon, highlighting the balance between cholesterol synthesis and energy homeostasis.
🚫 The Risks of Elevated Cholesterol Levels
This paragraph addresses the potential dangers associated with high cholesterol levels, particularly LDL cholesterol, which can lead to life-threatening conditions if not managed. It explains the use of statins like Lipitor to inhibit HMG-CoA reductase, thereby reducing cholesterol synthesis and lowering LDL levels. The importance of understanding cholesterol metabolism is emphasized, as it is integral to the synthesis of essential molecules and maintaining overall health.
🔄 The Complex Regulation of Cholesterol Metabolism
The final paragraph wraps up the discussion on cholesterol metabolism by emphasizing its complex regulation. It mentions the role of NADPH as a reducing agent in the synthesis process and how cholesterol levels can feedback inhibit HMG-CoA reductase. The interplay between insulin, which stimulates cholesterol synthesis, and glucagon, which opposes this action, is highlighted, showing the delicate balance required for proper metabolic function. The paragraph concludes by summarizing the key points covered in the video and inviting viewer engagement.
Mindmap
Keywords
💡Cholesterol Metabolism
💡Acetyl CoA
💡Bile Salts
💡Steroid Hormones
💡Lipoproteins
💡HMG-CoA Reductase
💡Statins
💡NADPH
💡Lipid Rafts
💡ACAT (ACholesterol Acyltransferase)
💡LDL (Low-Density Lipoprotein)
Highlights
Cholesterol metabolism is crucial for various bodily functions, including bile salt production for fat emulsification and steroid hormone synthesis.
Cholesterol is synthesized from acetyl CoA, a basic unit, through a series of enzymatic reactions primarily occurring in the liver.
Acetyl CoA can be diverted from the Krebs cycle into cholesterol synthesis, regulated by the hormone insulin.
The enzyme HMG-CoA reductase is a key regulatory step in cholesterol synthesis and is the target of statin drugs like Lipitor.
Cholesterol is an integral component of cell membranes, contributing to their structure and fluidity.
Cholesterol is used in the formation of steroid hormones such as testosterone, progesterone, estrogen, and cortisol.
Bile salts, synthesized from cholesterol in the liver, are essential for the emulsification and digestion of fats.
Lipoproteins are molecules that transport cholesterol and other lipids to different tissues in the body.
The enzyme ACAT is involved in converting cholesterol into cholesterol esters for packaging into lipoproteins.
Different types of lipoproteins, such as VLDL, LDL, and HDL, have distinct roles in lipid transport and cholesterol management.
High levels of LDL cholesterol are associated with health risks, and statins are used to lower cholesterol synthesis.
Cholesterol itself can inhibit HMG-CoA reductase, suggesting a feedback mechanism in cholesterol regulation.
NADPH is required as a reducing agent in the cholesterol synthesis pathway, highlighting its importance in various biosynthetic processes.
The balance between insulin and glucagon affects HMG-CoA reductase activity, influencing cholesterol synthesis and glucose production.
Cholesterol metabolism is intricately linked to other metabolic pathways, emphasizing its significance in maintaining overall health.
The video provides a comprehensive overview of cholesterol's role in the body and the complexities of its metabolic pathways.
Transcripts
iron engineers in this video we're going
to talk about cholesterol metabolism so
cholesterol metabolism is extremely
important because cholesterol is the
basic unit for a lot of different things
one of the things that we'll talk about
is four bile salts which are really
really important for being able to help
with the emulsification of large fat
globules that we take in through
ingestion they're also important for a
lot of the steroid hormones that we
utilize on our body like testosterone
progesterone estrogen vastra and
cortisol and they're also important
because they are actually packaged
there's specific molecules specifically
called lipoproteins and we'll talk about
a couple of them in this video we'll
have another video on more detail on
that but we'll talk a little bit about
how they're involved in actual transport
of cholesterol and then also it's a very
integral component of the membrane but
we'll talk about all that but the
significance of this whole video is to
see how we're going to be able to
synthesize cholesterol with a basic unit
of acetyl co a and how that can be used
for synthesis mechanisms we'll talk
about a couple enzymes along the way
okay so cholesterol metabolism is
primarily going to be occurring inside
of the liver we can take cholesterol in
through an exogenous pathway via through
the ingestion of foods and we can take
them transport them to different tissues
via what's called chylomicrons but the
endogenous pathway of cholesterol is
actually going to be taking place within
the liver so let's see how we do that
well if you guys remember from a lot of
these videos we could take a molecule
called glucose and we could take glucose
and what can we do with them if you guys
remember we could take glucose and we
could eventually convert that glucose
into pyruvate through glycolysis right
and then another thing we could do is we
could take that pyruvate and eventually
convert it into acetyl co a but what can
happen with the acetyl co if you guys
remember acetyl co a can actually go
through a specific sequence of cyclic
steps right which is called the Krebs
cycle and then from the Krebs cycle what
do you generate you generate a lot of
NADH is you generate a lot of fadh2s
even generate a little bit of ATP
through substrate phosphorylation but
these guys are generally taking their
information to thee what the electron
transport chain and what happens if the
electron transport chain you make ATP so
that is the overall goal of this process
right now what happens though whenever
we have too much acetyl co a what
happens if you guys remember the main
anabolic hormone I want you guys to
really really remember this one that
hormone was called insulin insulin is
the main anabolic hormone of the body
okay so insulin is extremely important
in this process of cholesterol
metabolism so what is he going to do
we'll talk about that in a second well
now let's see how this if there's too
much acetyl co a we already know that it
can go into two different pathways that
we talked about one was a tiny little
pathway we can say over here that we can
make ketone bodies if you guys remember
through ketogenesis
and then what can happen with these
ketone bodies if you remember they can
be taken up by two different specific
tissues the brain the central nervous
system tissue as well as the muscles and
can be utilized to make what they can be
utilized to make ATP but there's another
side pathway that we can push acetyl
COAS into and that is into a cholesterol
synthesis so now let's talk about that
so let's say that I take this acetyl co
a I put it right it'll actually no let's
bring it over here then let's say that I
take these acetyl co eggs and we start
here and see how this is all happening
so now acetyl co a let's say I take an
acetyl co a here and I take another
acetyl co a and I'm going to react these
two molecules together so I'm going to
take these two molecules and I'm going
to react them together so let's say I
react these two together and I'm going
to use them together when i fuse acetyl
co a and acetyl co a together there's a
special enzyme there's a lot of
different names for it but I like the
simple names it's easier for me to
remember so I like thiolase it's just an
easier time to remember as compared to
like acetyl co a acetyl transferase Idol
I just like the thiolase
okay but there is another enzyme that
you could utilize for this
step okay now in this step what am i
doing I'm taking a seat Ocoee and a CoA
and reacting them together in this first
step of the reaction but what am I going
to get out of this out of this I'm going
to produce a molecule called a cito
acetyl co a now this might seem very
very familiar if you guys have already
watched our ketone body videos the
actual beginning steps of this process
is going to be almost exactly the same
as the ketone bodies now we're not going
to go through every single step to make
cholesterol it's about 30 steps long so
to do that would be ridiculous we want
to get the significant components out of
this video but here's what we we need to
notice look at this we have acetyl co a
an acetyl co a how many of utica ways is
that that's I'm sorry how many Co ways
is that that's two Koei's then what I
did is I converted that into a cito
acetyl co a there's only one Co a there
so what did I lose in this stuff
I lost a co a so in this step I lost a
co enzyme a and I made a cito acetyl co
a now and the next step I'm going to do
this reaction and what I'm going to do
is I'm going to combine another molecule
and this next molecule is exactly the
same as what we had over here guess what
I'm going to have coming over here I'm
going to have a seat okole so I'm going
to feed another acetyl co a into this
reaction so now I'm going to take this
acetyl co a and feed it into this
reaction here okay so let's actually
show this in the same color then so that
we make it look all nice and Purdy
acetyl co a here with the acetyl acetyl
co a is going to react and what am I
going to do I'm going to lose another Co
a so out of this reaction what's going
to come popping out I'm going to pop out
a CO a now now I'm going to form a very
special molecule now there's two there's
actually two names for this the
abbreviation I'm just going to call it H
M G Co a but there is another name for
it I will mention it but it's easier to
do this one but it actually goes 3
hydroxy
three methyl blue Carol Calais or beta
hydroxy beta methyl gluten okay now you
guys probably get why I would just call
it a gym GK it's easier to say that but
the whole point is that we do have a
hydroxy group on the third carbon and
then we have a methyl group on the third
carbon and then it's a glute arrow kolay
okay what enzymes catalyzing this step a
very very important enzyme and this is
called hmg-coa synthase okay he is
catalyzing this stuff he's stimulating
this step to fuse acetyl coa with acetyl
co and make HMG coa now we go into the
most most important one of the most
regulated steps of all metabolism in the
entire body
okay let's make sure that we understand
that so I'm going to do this in a really
really thick red arrow here this is one
of the most regulated enzymatic steps in
the entire body
okay the enzyme that's regulating this
step here I specifically called h mg co
a reductase so hmg-coa reductase is the
rate limiting step here it's very very
important I'm going to put below it it
is the rate limiting step so it's one of
the slowest step it's one of the most
important and most regulated steps so
this is one of the most regulated steps
in our body here this step right here
why because it's very very crucial that
we regulate how much cholesterol is
being made so how do we do that well you
know you know there's actually drugs you
know people have really really high
cholesterol they have to take certain
types of drugs to be able to lower the
cholesterol you know how they actually
do it one of the drugs that you guys
have probably heard of called lipitor so
you've probably heard of the drug called
lipitor and we're like its branding the
lipitor lipitor is actually what's
called a statin so there's different
type of statins and statins are
basically just drugs that can come and
inhibit this enzyme
so this hmg-coa reductase could be in
by certain types of drugs which can
inhibit the cholesterol synthesis which
is good for people who have high
cholesterol levels they've been eating
too much Burger King too many whoppers
right so we need to cut that down take
their lipitor and watch what they're
eating but anyway this HMG co-reductase
is very very important because it's
what's controlling the conversion of HMG
calais and to another very important
molecule which is going to be the
precursor so this molecule is called
methyl on it Armel ilanic acids doesn't
matter I'm just going to call it neva
law neat so this next enzyme again is
called methyl on eight
now methyl on e is actually important
because he's going to be the precursor
for the synthesis of cholesterol now
like I said we're not going to go over
every single enzymatic step it's
ridiculous there's so many will come
some of the more significant ones like
you know mevalonic can actually be
converted into another molecule which is
called isopentyl pyrophosphate so that
molecule is called ISO pencil pyro
phosphate now why am i mentioning this
because whenever this methyl Ani he goes
through a couple steps and eventually
gets converted into isopentyl
pyrophosphate isopentyl pyrophosphate
is going to be kind of the building
block for this also because what happens
is I'm going to take a whole bunch of
different types of isomerase forms of
the isopentyl I saw pyrophosphate or
just the isopentyl pyrophosphate itself
and I'm going to combine a ton of them
I'm talking boatloads of these isopentyl
pyrophosphates and eventually I'm going
to form a very special molecule and this
process right here I'm completely
bypassing a lot of important information
here or I'm sorry not a lot of
information because you know just for me
to convert this isopentyl pyrophosphate
into this next molecule this next
molecule is called squalene
so isopentyl pyrophosphate technically
in between here if I were to actually
kind of have an in-between step here
isopentyl pyrophosphate let's actually
just do it here in this step I just do
here we say that we take the isopentyl
pyrophosphate and I take and I actually
convert that and to these molecules
which are called isoprene units I so
preen units and these isoprene units are
important because it takes a ton of
isoprene units to eventually get
converted into a very important molecule
called squalene okay so now we'll talk
about the scaling so squalene in order
for me so this is a complete
oversimplification because simply going
from these isoprene units to the scaling
can take up to 21 steps so let me write
that down because it's significant me
going just from the isoprene units to
the scaling it can take up to 21 steps
now one of the more important enzymes in
throughout this process green is called
squalene synthase and the squalene
synthase is an environments helping with
in these processes to convert these
isoprene units into squalene now
squalene is then going to be the
precursor to make another molecule and
this molecule is called 7d hydro
cholesterol so 7d hydro collector I
guess apply heard of that whenever we
talk about the parathyroid hormone with
toughly to make vitamin D so you can
actually make vitamin D from this point
here but look we're going to make
another molecule called 7d hydro
cholesterol then what happens at 7d
hydro cholesterol okay now here's where
we get into the good stuff so now this
7d hydro cholesterol what can happen
with this molecule there's 70 hydro
cholesterol I'm going to put this
squealing synthase under here that we
have some room to come back down again
this is called squalene synthase now
here's where it's important so let's
make this a really big line here
7d hydro cholesterol
can be converted into the molecule that
we know as cholesterol so in this
process here what am i doing I'm taking
the 7d hydro cholesterol and I'm
converting it into a molecule called
cholesterol now this cholesterol that
I'm making you it's crazy to see how we
just take these two carbon fragments
acetic aways and we synthesize a huge 27
carbon molecule like you would guys want
to know what I a cholesterol looks like
I'll tell you I know you guys are
excited you guys are chomping at the bit
to see the structure of cholesterol so
look here because I know you guys are
chomping at the bit for so look I'm
going to have three six carbon rings
like this right then I'm gonna have
another six carbon ring like this and
then I'm going to have a five carbon
ring like this then I like to put a
methyl right here and a methyl right
here
so now let's number all of these puppies
here this right here is number one two
three four then I'm going to come over
here to five six seven eight nine and
then I come to this last point here ten
okay
then I'm going to come up over here 11
12 13 I'm going to go over here 14 15 16
17 then we come over here
18 19 but I told you all the way exact
you said it was 27 it is 27 coming off
of the 17th carbon I'm going to have a
branch like that 1 2 3 4 5 so 1 2 3 4 5
and then like this and now let's count
these carbons over here 17 18 19 this is
going to be 20 21 22 23 24 25 26 27 why
am I telling you all this because
there's important points throughout all
of this on the third carbon there's a
special thing that's going to determine
the difference between certain types of
steroid hormones on that third carbon
there's usually a alcohol okay and then
in between the fifth
in the six-carbon there should be a
double bond so now I like to just call
this a ring the B ring C ring and the D
ring and then you got this little
antenna structure this is our
cholesterol molecule now we synthesize
this cholesterol what is this
cholesterol used for because it's
extremely important we said that it's
important to be able to take this
cholesterol and synthesize a bunch of
different structures so now let's take
this cholesterol and see what we can
actually do with this cholesterol okay
so I told you that I could take this
cholesterol molokai I'm not going to
drill every single carbon again I'm just
going to take this carbon unit so that
you can see that we have cholesterol
here and what we're going to do with
this cholesterol is we're going to take
this cholesterol and use it to make a
whole bunch of different molecules and
again we can if you want to a ring B
ring C ring D ring okay what I can do
with this cholesterol is I can put it
into the actual cell membrane you're the
cell membranes are really important why
why is the cell membrane important let's
say that I have here the cell membrane
and in the cell membrane here you know
we have phospholipids that are making up
the actual cell membrane if I were to
kind of zoom in on this a little bit
let's say here's my glycerol okay and
then coming on one side have the fatty
acids right but you know that this
specifically the cell membrane is a
lipid bilayer so on the other side I'll
also have another group of phospholipids
but now here's the important thing
phospholipids are you know they're
they're basically they can make things
not as fluid like but cholesterol is
making it better and not being so fluid
like making a little bit more rigid so
if I take this cholesterol molecule and
I put this cholesterol molecule into the
structure let's say I erased this part
here and I put my cholesterol molecule
in here so now what I do is I take my
cholesterol molecule and I incorporate
this cholesterol molecule into this
structure
what is that going to do what this does
is it's actually first off it does two
things two things that this does being
cool incorporate into the membrane one
is it makes the membrane less fluid like
Les like les fluidity less fluidity okay
that's one thing so it's going to make
it less fluid the other thing it's going
to prevent drastic changes in phase
transitions so changing from different
phases so it prevents it prevents phase
transitions you know it's another
important thing it's also combining with
a molecule that is present in this area
let's say here I have a molecule special
molecule that it's combining with to
form a very special structure what is
this green molecule here called this is
called glyco sphingo lipids
so these glycosphingolipids are
combining with the cholesterol and as a
structure they're forming this whole
thing here if I were to kind of encase
it here they're forming what's called
the lipid raft which is important in
certain types of signaling pathways as
well as a lot of other processes so
again what's one thing that we can do
with this cholesterol right away one
thing I can do with this cholesterol is
I can incorporate this cholesterol into
the cell membranes because it's
naturally in normal physiological levels
is helping the membrane become less
fluid helping it to be more rigid and
hold up its actual structure the other
thing is preventing excessive phase
transitions okay also it's combining
with these glycosphingolipids within the
cell membrane to form lipid rafts
structures which are important for a lot
of different functions like cell
signaling processes what else can we do
with the cholesterol so that's one thing
we can do with it another thing that we
can do with this is we can take and
convert it into steroid hormones steroid
hormones are very very important so I
can actually make steroid hormones what
kind of steroid hormones can I make you
know there's many many different types
of steroid hormones
we talked about some of them and
endocrine I can make testosterone I can
make estrogen I can make corticosteroids
which includes your out dosterone and
your cortisol I can make tons of
different things progesterone a lot of
different molecules that can come from
this right so we can make steroid
hormones we can make progesterone
testosterone estrogen a lot of different
corticosteroids like cortisol AB astron
can add a corticoids so many different
types of things that we could do with
this so that's another basic unit for
the cholesterol so cholesterol can be
used for its cell membrane structures
steroid hormones what how it's going to
be used for it also could be used for
bile salts you know there's these things
called bile salts and these vile salts
are important because bio salts are
important you know there's let's call
Kolok acid there's called Kolak acid and
then there's another one called
deoxycholic acid and these are bile
salts and they're important for what you
know they're important we actually make
this in the liver and they're
incorporated into the bile which is
excreted into the small intestine like
specifically the duodenum what does that
help for it it helps with the
emulsification of lipids you know taking
lipids that are very very water
insoluble and trying to make them more
water-soluble by spreading them out into
smaller fatty droplets that we'll talk
about called me cells okay and a lasting
we'll have another video specifically on
this in detail but you know what else we
can do with that cholesterol we can
package this cholesterol and we can send
it to other tissues so I can actually
package this cholesterol and to do
special lipoprotein molecule so let's
say I take that cholesterol but you know
in order for me to take this cholesterol
and put it into this actual vesicle I'm
sorry this lipoprotein structure I need
a special enzyme and this enzyme is
called a cat
and a cat is an enzyme that basically
converts cholesterol into a cholesterol
ester so again what what am i convert so
if you guys remember here on the a on
that third carbon I had an alcohol what
I'm going to do is I'm going to take in
this vesicle here I'm going to convert
inside here I'm going to take and I'm
going to basically take and add an acyl
group onto it so you know a cat is
basically an ACO Co a and specifically
what I'm doing here is I'm transferring
on a a so group so in other words let me
show you what I'm doing here so I'm
going to take that actual group here I'm
going to put on a double bond like I see
CH 3 there so let's say I add on a 2
carbon group there now this is a
cholesterol ester and if I were to draw
the rest of the structure here you guys
would get the point here that basically
I'm packaging this molecule into a nice
big vesicle so let me draw a big vesicle
here lipoprotein molecule so now this
lipoprotein is going to have my
cholesterol ester in it so again what is
this molecule here called this is a
cholesterol ester and this a cat enzyme
is transferring that a co group that 2
carbon group onto the cholesterol
molecule so it's acting as a a co
cholesterol transferase enzyme and then
after we package this into a protein
covering so now this is actually going
to be the actual cholesterol component
and around that I'm going to have my
protein component and on the protein
component I can have specific types of
April proteins that we'll talk about
depending upon the type of life of
protein it is so for example this can be
one type you know what this one is
actually then we can actually call this
one LDL bad cholesterol okay and this
one is actually very dangerous if it's
if there's really really high LDL levels
that's why whenever people have high
cholesterol mainly LDL you want to give
them statins or lipitor because if you
remember that's going to inhibit the
hmg-coa reductase enzyme so you don't
make as much cholesterol so you can't
utilize it in the lipoprotein pathway so
again what is the small
you're called it's called a lipo
proteins so it's very important for
making lipo proteins which can go and
get transported to other different
tissues you know there's another one
that you can make here there's another
one it's actually called VLDL we talked
about that in the triglyceride synthesis
video the only difference is is that
instead of having a significant amount
of cholesterol you also add in
triglycerides triglycerides are also
added into the vldls and significant
amount there's a lot of triglycerides
and not as much cholesterol esters but
nonetheless your liver can make vldls
and LDL s it can also make other
lipoproteins which you guys are probably
heard of called HDLs which are going to
help for being able to pull some of the
cholesterol off of the vessel walls but
we'll have an individual video on that
but again understanding all of this is
important but understanding the
significance of why the cholesterol
metabolism is occurring is more
important understand that I can use this
for synthesis pathways incorporating
into the cell membrane making steroid
hormones making bile salt and actually
helping to make lipoproteins for other
different tissues because if you imagine
LDL is actually taking and transporting
some of that cholesterol to like the
adrenal cortex you know in the adrenal
cortex they need that cholesterol they
need that cholesterol to be able to make
their steroid hormones so it's very
important that we have that cholesterol
so taking it to the testes to be able to
make testosterone and estrogen so
without that there could actually be
potential like life-threatening problems
but too much of it is also pretty bad
and again knowing that out of this this
is one of the most important metabolic
steps in the entire body you know not
only lipitor isn't actually inhibiting
this oh and another thing I'm so sorry I
didn't mention this this step right here
we need NADPH too in a dp+ if you guys
remember this was a very very strong
reducing agent and we need him in this
step because of his reducing power NADPH
is utilized in a lot of different
pathways you know not just in steroid
synthesis not just in triglyceride
synthesis but also for nucleotide
as well and even to train the synthesis
of neurotransmitters - so NADPH is
actually utilized in this step but
remember this is a highly regulated
enzyme another thing that can actually
inhibit this guy at this point here is
also going to be cholesterol cholesterol
itself can inhibit this HMG co-reductase
so high amounts of cholesterol can act
on this hmg-coa reductase and actually
inhibit the synthesis of himself he does
it by activating specific proteolytic
enzymes so he activates proteolytic
enzymes that will actually help to
specifically inhibit this hmg-coa
reductase but like I told you before
insulin is also extremely important
because insulin is also going to try to
stimulate this enzyme activating this
enzymes for certain types of second
messenger intra cellular pathways to
stimulate this enzyme whereas the actual
guy who tries to oppose insulin is
glucagon and you guys know that glucagon
wants to be able to do what - this
enzyme he wants to inhibit this enzyme
inhibit the actual synthesis of
cholesterol use it for making glucose
use that ASC decoy to make glucose or to
help to be able to generate ATP instead
primarily let it make glucose okay so
very very highly regulated enzyme here
alright so in this video we covered a
lot of information I hope it all made
sense I hope you guys really did enjoy
it I hope it clicked if it didn't if you
guys enjoy - hit that like button
subscribe put a comment down in the
comment section guys we really look
forward to hearing from you guys
alright engineers until next time
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"숫자에 집착하지 마세요." 콜레스테롤 수치보다 더 중요하게 봐야할 것 (이승훈 교수 3부)
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