Metabolism | Cholesterol Metabolism

Summary

This 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

00:00

🧬 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.

05:02

🛠️ 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.

10:02

🌱 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.

15:03

🔬 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.

20:06

🚫 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.

25:07

🔄 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.

Keywords

💡Cholesterol Metabolism

Cholesterol metabolism refers to the biochemical pathways involved in the synthesis and breakdown of cholesterol in the body. It is central to the video's theme as it forms the basis for understanding cholesterol's role in health and disease. The script discusses how cholesterol is synthesized from acetyl CoA and its various functions, such as being a component of cell membranes and a precursor for bile salts and steroid hormones.

💡Acetyl CoA

Acetyl CoA is a central molecule in metabolism, acting as a substrate for various biochemical reactions, including the synthesis of cholesterol. In the context of the video, acetyl CoA is the starting point for cholesterol synthesis, highlighting its importance as a building block for more complex molecules. The script details how two acetyl CoA molecules combine to form a key intermediate in cholesterol production.

💡Bile Salts

Bile salts are detergent-like substances that emulsify fats in the small intestine, aiding in their digestion and absorption. They are synthesized from cholesterol in the liver. The script emphasizes their importance in the digestion of fats and their connection to cholesterol metabolism, illustrating the multifaceted role of cholesterol in the body.

💡Steroid Hormones

Steroid hormones are a class of hormones that include testosterone, estrogen, and cortisol, among others. They are derived from cholesterol and play critical roles in various physiological processes. The video script explains how cholesterol serves as a precursor for these hormones, underlining its significance in endocrine function.

💡Lipoproteins

Lipoproteins are complex particles that transport lipids, including cholesterol, through the bloodstream. The script mentions different types of lipoproteins, such as VLDL, LDL, and HDL, and their roles in cholesterol transport and health. Understanding lipoproteins is essential for grasping how cholesterol is distributed and utilized in the body.

💡HMG-CoA Reductase

HMG-CoA reductase is a key enzyme in the cholesterol synthesis pathway, catalyzing the conversion of HMG-CoA to mevalonate. The video script highlights this enzyme as a rate-limiting step and a major target for cholesterol-lowering drugs called statins, such as Lipitor, emphasizing its regulatory role in cholesterol production.

💡Statins

Statins are a class of drugs that inhibit HMG-CoA reductase, thereby reducing cholesterol synthesis in the liver. The script discusses statins as a treatment for high cholesterol levels, illustrating their clinical relevance and their mechanism of action in managing cholesterol metabolism.

💡NADPH

NADPH is a reducing agent crucial for numerous biosynthetic pathways, including cholesterol synthesis. The script mentions NADPH as a required cofactor for the conversion of HMG-CoA to mevalonate, indicating its importance in providing the necessary reducing power for this reaction.

💡Lipid Rafts

Lipid rafts are specialized microdomains within the cell membrane, enriched with cholesterol and sphingolipids. They play a role in cell signaling and membrane trafficking. The video script describes how cholesterol, along with glycosphingolipids, contributes to the formation of lipid rafts, highlighting cholesterol's structural and functional importance in cell membranes.

💡ACAT (ACholesterol Acyltransferase)

ACAT is an enzyme that converts cholesterol into cholesterol esters, which are more easily packaged into lipoproteins for transport. The script explains the role of ACAT in the formation of cholesterol esters, which are then incorporated into lipoproteins like LDL, emphasizing the enzyme's function in cholesterol transport and regulation.

💡LDL (Low-Density Lipoprotein)

LDL, often referred to as 'bad cholesterol,' is a type of lipoprotein that transports cholesterol to tissues. High levels of LDL are associated with cardiovascular disease. The script discusses LDL in the context of cholesterol transport and its clinical significance, especially in relation to statin therapy.

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

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comment section guys we really look

forward to hearing from you guys

alright engineers until next time