what is a lipid
chemically diverse group of compounds which are not soluble in water but soluble in non-polar organic solvents – contain
how are lipids usually related to fatty acids
they contain fatty acids or they are made from fatty acids
is cholestrol a lipid
Cholestrol is a sterol, but many regard it as a lipid and does not contain fatty acid but can attach to a fatty acid
problem of lipid transport around the body
not soluble in water – problem when transporting around the body in blood, plasma of the blood is water based so lipids wont dissolve in it
what is a fatty acid
long hydrocarbon chain (containing carbon & hydrogen) with a terminal carboxyl (COOH) group
what is the general formula of a fatty acid
CH3(CH2)nCOOH
n is a variable number
how many carbons do fatty acids in plants and humans have
even number of carbons
how many carbons do fatty acids in bacteria usually have
Uneven usually produced by bacteria
why can we sometimes have uneven number carbon fatty acids
we can ingest bacteria, these an end up in our tissues (animals don’t make them)
what forms of fatty acids are there in the body
triacylglycerol phospholipids free fatty acids glycolipids cholesterol ester
what is triacylglycerol
fat
adipose tissue
what is the biggest amount of lipid in the body
triacylglycerol
what is adipose tissue importance
biggest store of energy, cant survive without it
what are phospholipids
major component of all membranes
what do the most abundant phospholipids in the body contain
have a glycerol backbone, have two fatty acids attached to them and on third carbon of glycerol is phosphate and alcohol group
what are free fatty acids
Non-Esterified fatty acids (NEFA) not attached to anything
plasma
what are glycolipids
carbohydrate and lipid
what is cholesterol ester
cholesterol with fatty acid attached to it, storage form
what is the fatty acid level like in the blood when we awake before eating
before eating when wake up will be high level
When not eating and asleep, no stimulation to produce insulin, fat tissue starts to break down some reserves and break down some triglycerol release non-esterified fatty acids
what happens to the fatty acid level in the blood when we consume food after sleeping
after eaten will lower due to regulation of fatty acid release due to insulin
soon as eat insulin rises, turn off enzyme e which breaks down the fat and levels of fatty acid go down
what are the major biological roles of fatty acids
energy storage and production
protection/insulation
biological membranes
precursors of other bioactive molecules
why is it important to have energy storage and production
if couldn’t do this our meals would have to match our requirements exactly – would have to graze all day release excess stored energy
what provides protection and insulation - fatty acids
triacylglycerol
what is the importance of phospholipids in membranes
isolate cell/organelles from outside environment
allow communication with outside environment (not completely sealed)
protect from outside, keep certain molecules in and others out
what bioactive molecules are fatty acids precursors of
eicosanoids
what are examples of eicosanoids
prostaglandins
prostacyclins
thromboxanes
leukotrienes
what are eicosanoids
all are local hormones, immediate effect on cell itself or cells surrounding it
what is the structure of triacylglycerols
Esters of 3 Fatty Acids with glycerol backbone
what is the structure of phospholipids
Esters of 2 Fatty acid with glycerol backbone
3rd carbon of glycerol attached to a phosphate group + another alcohol (often containing nitrogen)
what are the three fatty acids like that are attached to the triacylglycerol
Rare for the three fatty acids to be the same only usually happens if artificially manufactured triacyglycerols for any reason they want to have it completely homogenous
what is triacylglycerol like at room temperature
Triacyglycerol that was a long chain of saturated fatty acids very solid at room temp
what are unsaturated fatty acids like at room temperature
Unsaturated fatty acids are flexible at room temperature – give membranes flexibility (when talking about phospholipids too)
how can fatty acids differ
chain length number of double bonds * none = saturated * 1 = monounsaturated * >1 = polyunsaturated position on the chain of the double bonds type of double bonds (cis and trans)
how many carbons do most fatty acids have
16-18
what double bond if mainly found in nature
cis
what double bond is mainly found in bacteria
trans
why would we sometimes have trans double bond fatty acids in our body
if we ingest bacteria with them
what is a cis double bond
carbons both on the same side
what is a trans double bond
carbons on opposite sides
how can trans double bonds be formed
Can get trans fatty acids by chemically hydrogenating fat
why is a cis bond fatty acids fluid at room temperature
Cis bond put bend in the fatty acid, so fluid at room temp
why is a trans bond fatty acid solid at room temperature
Trans bond has a straight chain, behaves more like a fatty acid, solid at room temperature
what effect is there is a cis bond is changed to a trans bond
changes the nature and the biological properties
how can fatty acids be named
- if start from carboxyl end name them based on the number of double bonds carbon length - if start from the methyl end which omega family they're in
what does omega-x- denote in naming fatty acids
Omega-x- denotes the position of the first double bond from the orange end
methyl end
what does delta-x- denote in naming fatty acids
Delta-x- similar to systematic in that it describes the position of double bonds from the carboxyl end
which end should we name from in fatty acids if we want to put it into a ‘family’
methyl
will group into omega 3, 6, 9
what family would fatty acids from methyl end with first double bond from the third be in
omega 3
what are all polyunsaturated fats made from
monounsaturated fatty acids by further desaturations (more double bonds)
what fatty acids can can animals make
only major ones animals can make de novo are based on oleic acid
what effect do animals have on fatty acids
insert double bonds between existing bond and carboxyl group
where do we get linoleic acid and alpha-linolenic acids from
Plants can make both linoleic acid and alpha-linolenic acid we can consume these as we need them, we can change them when they’re in out body
can’t make linoleic acid or α-linolenic acid from oleic acid enzymes cant put the double bond the other side of the existing double bond, it has to be from the carboxyl end
what effect do plants do to fatty acids
insert double bonds between existing bond and methyl group
what are fatty acids important for
Play a vital role in membrane function
Are the precursors of eicosanoids
what are MUFA
mono unsaturated fatty acids
what are PUFA
poly unsaturated fatty acids
how does 2C acetyl CoA go to 3C
Acetyl CoA carboxylase enzyme adds another carbon onto acetyl CoA to make malonyl CoA
how does 3C malonyl CoA go to 16C
Fatty acid synthase enzyme adds two carbons to make palmitic acid
how does 16C palmitic acid go to 18C
Elongase enzyme adds two carbons to make stearic acid
how does 18C go to 18C with a double bond (monounsaturated)
Delta9-desaturase enzyme insert double bond to make oleic acid
when is ATP produced from acetyl CoA
Produce ATP when acetyl CoA broken into CO2 – need energy
how is acetyl CoA transported into the cytosol
Acetyl CoA itself wont cross mitochondrial membrane, have to temporarily make it into citrate molecule by combining it with oxaloacetate
Specific transporter lets citrate across membrane
When citrate on other side it is broken down again to get acetyl CoA
Oxaloacetate is broken back down into pyruvate which moves back into the mitochondria
where is acetyl CoA made
mitochondria
where are fatty acids synthesised
cytosol
what mechanism is used to transport acetyl CoA
So need to get it out the mitochondria by using a shuttle mechanism
in fatty acid synthesis what is the rate limiting enzyme
Acetyl CoA carboxylase, first step which regulates the rate at which fatty acids are made
what is the fatty acid synthesis of prokaryotes
synthesis occurs due to the action of a series of separate enzymes
what is the fatty acid synthesis of eukaryotes
synthesis occurs through the action of a multifunctional enzyme complex
what is linked to acyl carrier protein
Intermediates in fatty acid synthesis
what is ACP
acyl carrier protein
what is ACP in bacteria
77 amino acid protein joined to a phosphopantetheine (PP) group
what is ACP part of in animals
part of the fatty acid synthase complex
what is the acetyl transacylase reaction
Acetyl CoA joins with ACP temporarily form acetyl ACP+CoA
what is the malonyl transacylase reaction
Malonyl CoA joins with ACP temporarily form malonyl ACP+CoA
what does fatty acid synthase system do
synthesizes long chain saturated fatty acids
what does the fatty acid synthase system involve in prokaryotes
four separate enzymes
what are the substrates in fatty acid synthase
Acetyl-ACP
Malonyl-ACP
NADPH
what are the steps in the fatty acid synthase reaction
Start with acetyl ACP 2C fatty acid, reacts with malonyl ACP 3C, requires reducing power from 2 NADPH molecules
NADPH oxidized to make NADP+
One of the carbons from malonyl CoA lost as CO2
Lose some water
2 carbons from malonyl-ACP added to acetate to make butryl-ACP 4 C
what process occur in the fatty acid synthase reaction
- Condensation
- Reduction
- Dehydration
- Reduction
what happens in chain elongation
Every step added another two C
Lose a C as CO2
what is chain termination
uses a water from synthesis of palmitate
carbon chain tend to stop at C16, release palmitic acid
what releases palmitic acid in chain termination
thioesterase enzyme
where are shorter chains usually released (chain termination)
Some shorter chain fatty acids are also released, particularly in mammary gland
what is the major product of fatty acid synthase reaction
palmitic acid
how many carbon atoms are in 60% of fatty acids
60% of fatty acids in human adipose tissue have 18 Carbon atoms
where are fatty acids from
Diet (plants and animals)
Further metabolism of palmitate - Can further elongate palmitate and add extra two carbons and make 18 carbon fatty acids
where is palmitic acid made
cytoplasm
where is stearic acid made
Some of the palmitic acid moves to the endoplasmic reticulum
Palmitic acid to stearic acid, adding two extra carbons using elongase occurs on endoplasmic reticulum
where is oleic acid made
Also on endoplasmic reticulum stearic acid made into oleic acid, delta9–desaturase acts on the ninth carbon from carboxyl end and can insert double bond between ninth and tenth carbon probably
what is the most abundant fatty acid in nature
Oleic acid
name some important1-acyl glycerol phosphate 2-acyltransferase phospholipids
phosphatidylcholine
phosphatidylethanolamine
phosphatidylserine
phosphatidylinositol
what are phospholipids important in
major components of biological membranes
role in cell signalling
what is the difference in the first step of triacylglycerol and phospholipids synthesis
they’re the same
glycerol-3-phosphate converted to lysophosphatidate
a fatty acid, which is attached to Co factor Co enzyme A
Release fatty acid from Co enzyme A and join it to the first carbon
G-3-P produces lysophosphatidate (added a fatty acid on first carbon)
Often is a saturated fatty acid added on first carbon
what are glycerol-phospholipids
all phospholipids with glycerol backbone
what is phosphidate
Phosphatide is a glycerol with two fatty acids, one on first carbon, second on second carbon
what happens to lysophosphatidate in triacylglycerol and phospholipid synthesis
Fatty acid joined to Co enzyme A, released from enzyme and fatty acid joins to second carbon
what does triacylglycerol and phosphoplipid synthesis start with
Normally start with a glycerol that has phosphate on third carbon – glycerol-3-phosphate
what can happen to phosphatidate
can take 2 routes phosphatide can take
Can remove phosphate group from third carbon using phosphatidate phosphohydrolase enzyme, so replaced with hydroxyl group – diacylglycerol
Take nucleotide CTP, and CDP molecule added to last carbon form CDP-diacylglycerol
what causes the different routes for phosphatidate
Depending on the metabolic state of the cell, and requirements of cell which is made
how can phosphatidate form triacylgylcerol
Form diacylglceryol by adding another fatty acid to last carbon to form triacylglycerol
what does diacylgylcerol make
Phosphotidylcholin and Phosphotidylethanolamine phospholipids, these make Phosphotidylserine
what does CDP-diacylgylcerol form
Phosphotidylinostitol
what does phosphidate form
diacylglycerol
CDP-diacylglycerol
what happens in lipid transport
eat them, digest and absorb them need to move fatty acids round body to different tissues often directly to adipose tissue
Plasma of blood is water based media
Transport out of intestine
why is it important to be able to store
need to be able to mobilise that energy when fasting as a source of energy
where are lipids made
Store and make lipids in liver, then has to mobilise and transport them
where are lipids stored
adipose tissue
where are lipids used
muscles
where are triacylglycerols stored
Adipose tissues
what are NEFA
non-esterified fatty acids
what happens with non-esterified fatty acids in lipid transport
NEFA can be released from adipose tissue and loosely stick to protein, albumin –major protein in blood produced by the liver, has hydrophobic regions on it which fatty acids seek out and temporarily attach to transported to muscle and released. Taken into muscle cells and used as energy source
what happens with intestine and liver in lipid transport
Intestine and liver make complicated particles – lipoproteins. Is a sphere, ball shaped lipoprotein has a coating of phospholipids hydrophilic due to the polar heads being on the outside, so will physically dissolve in the plasma
what is a lipoprotein like
Hydrophobic fatty acid tail on inside
molecules of cholesterol dotted in the outer coating
Lipids inside that don’t like water e.g. triacylglycerol extremely hydrophobic
what is cholesterol ester like
very hydrophobic
what are the components of lipoproteins
proteins - apolipoproteins
phospholipids - phosphatidylcholine most abundant
triacylglycerol
cholesterol and cholesterol ester
where is cholesterol in lipoproteins
free cholesterol at surface
where is cholesterol ester in lipoproteins
attached to fatty acid in core
how do lipoprotein classes differ
protein/lipid ratio
phospholipid/cholesterol/cholesterol ester/ triacylglycerol ratio
specific proteins present
how do physical difference occur in lipoprotein
size
Density (chylomicrons big but light as full of lipid)
Charge (depends which proteins they have, can separate individual lipoproteins using gel electrophoreis)
which lipoproteins are not named by classification
Lipoproteins produces by intestine not named by classification, these are the chylomicrons
why do many chylomicrons float
are less than 1 density so float
water is 1
what is VLDL
very low density liopoprotein
density lessthan 1.006
what is IDL
intermediate density lipoprotein
what is LDL
low dense lipoprotein
what is HDL
high dense lipoprotein
why must those who’s lipid profile is being measure told to not to eat
chylomicrons are hard to completely seperate from VLDL
what are apolipoproteins
diverse group of proteins that associated with lipoproteins
how come apolipoproteins can jump around different molecules
most proteins are only loosely associated with surface
what are the apolipoproteins functions
structural
enzyme activators or inhibitors
receptor recognition
what are the apolipoproteins structural function
Hold particle together
e.g. ApoB48 & ApoB100
what are the apolipoproteins enzyme activators or inhibitors function
e.g. Apo CII – activates lipoprotein lipase/ ApoCIII - inhibits lipoprotein lipase
what are the apolipoprotein receptor recognition functions
Recognised by receptors on the surface of cells
e.g. ApoB100 recognised by LDL receptor
what does e.g. B48 in a apolipoprotein mean
B48 is 48% of the size of B100
which lipoprotein is the most simple
LDL as only has B100
what are the lipoprotein synthesis and secretion paths
exogenous path
endogenous path
reverse cholesterol transport path
what happens in the exogenous path of lipoprotein metabolism
Dietary fats mainly fatty acids leave intestine in a chylomicron released into lymphatic system, enter blood stream, catches chylomicron, anchored to it
enzyme breaks triacylglycerol inside and release fatty acids
Chylomicron delivers a lot of its fat to adipose tissue, producing chylomicron remnants
Chylomicron remnant is delivered to the liver
what happens in the endogenous path of lipid metabolism
VLDL released from liver into circulation, pass into capillaries of tissues, interacts with lipoprotein lipase, either in muscle or adipose tissue
VLDL acted on lipoprotein lipase, breaks down triacylglycerol inside it, releases fatty acids and migrate to tissues
Remnant particle of VLDL is IDL, half of the IDL directly removed
how can heart disease be caused
Some LDL can be deposited in arteries = bad, causes heart disease
what happens in the reverse cholesterol transport path
Nascent HDL grows round the body and picks up cholesterol and delivers it to liver
Liver takes large amounts of cholesterol
Tissues cant break cholesterol
where is VLDL made
liver
where does most VLDL get directed
most VLDL will be directed to muscle rather than adipose tissue
how is the remnant IDL removed in lipoprotein metabolism - endogenous
circulates through the liver (50% removed from liver by interacting with receptors) and other 50% is acted on by another enzyme hepatic lipase, which is in the liver further breaks it to LDL
Of the LDL 80% circulates back to the liver and is removed and the other 20% taken up by peripheral tissues
what is crucial in regulating LDL
Liver is crucial in regulating how much LDL is in the blood
why is there competition in lipoprotein metabolism
Competition for LDL between these two paths
Both occur simultaneously
what is the tissue of origin for exogenous
intestine
what is the tissue of origin for endogenous
liver
what is the exogenous particle
chylomicron
what is the endogenous particle
VLDL
what is the site os secretion for exogenous
lymph/blood
what is the site of secretion for endogenous
blood
what is the exogenous ApoB form
apoB48
what is the endogenous ApoB form
apoB100
what is the exogenous remnant
chylo remnant
what is the endogenous remnant
IDL/LDL
what is the site is uptake for exogenous
liver
what is the endogenous site of uptake
liver/peripheral
what is the exogenous receptor
LRP/LDL
what is the endogenous receptor
LDL
what is the exogenous ligand
apoE
what is the endogenous ligand
apoE/apoB100
what is LCAT
lecithin:cholesterol-acyl transferase
what shape is newly formed HDL
disc-shaped
what happens when cholesterol and phospholipid combine
use LCAT enzyme
form
- cholesterol ester
- lysophospholipid
how is HDL converted to spherical HDL
Cholestrol ester moves to center of the partical (as hates water)
and becomes a spherical lipoprotein
when does HDL3 become HDL2
HDL3 continues to accumulate cholesterol ester and makes HDL2
HDL moves round body getting more cholesterol
HDL2 goes to liver when cant physically collect more, then liver can make them into e.g. bile acids, then excreted in faeces, major way to remove cholesterol
how is cholesterol removed from HDL2
HDL2 will associate to the liver and pump the cholesterol ester into the liver, shrinks to become HDL3 and then goes to collect more cholesterol ester
what happens to fatty acids when they get into cells
adipose tissue
liver
muscle
what happens to fatty acids in adipose tissues
stored as triacylglycerol (energy source)
what happens to fatty acids in liver
form either
- triacylglycerol phospholipid
- acetyl CoA which forms CO2 and ketone bodies
what happens to fatty acids in muscle
acetyl CoA forms CO2
In the fast state/starved can used acetyl CoA, feed into TCA cycle to make energy it needs
what energy is used in fed state
will mainly use glucose
when is ketone bodies made
if starving the acetyl CoA may be used to make ketone bodies as an alternative fuel for body
In starvation fatty acids can be used for ketogenesis to make ketone bodies
what is adipocyte
adipose tissue
what is the structure of fatty acid in adipose tissue
Big droplet of lipid in centre of cell cytoplasm tends to be pushed towards the outside, nucleus often pushed against plasma membrane
what causes liver disease
when obese resistant to insulin, so cant break down the lipid droplets – main cause of liver disease
what happens to fatty acids in fasted state
most FA will go muscle
where does and what is glycogenesis
Liver capable of taking glucose and fructose made into sugar glycogenesis
how can the liver use fatty acids in liver to get energy
Liver can use some for beta oxidation to get some energy
Fatty acids fed into beta-oxidation, breaking down fatty acid to acetyl CoA then used in TCA cycle to get ATP
what is the alternative energy source for muscles
muscle use fatty acids
if low glucose
in fed state what is the fatty acid metabolism in muscle
in fed state can be from chylomicrons
In both the fed and fat state can be from VLDL, fatty acids released by lipoprotein lipase
in the starved state what is the fatty acid metabolism in muscle
can be from non-esterified fatty acid released through adipose tissue
what are the three sources of fatty acids for energy
Released by LPL from chylomicrons
Released by LPL from VLDL
Released as NEFA from adipose tissue
what is the overall energy yield from palmitic acid
106 ATP
what is the site in the cell of fatty acid synthesis
cytosol
what is the carrier molecule of fatty acid synthesis
ACP
what is the site in the cell of fatty acid oxidation
mitochonria
what is the carrier molecule of fatty acid oxidation
CoEnzyme A
what is the enzymes fatty acid synthesis
multifunctional enzyme
what is the enzymes fatty acid oxidation
separate enzymes
what is the carbon units fatty acid synthesis
2C added from (3C) malonyl-CoA
what is the carbon units fatty acid oxidation
yields (2C) acetyl-CoA
what is the CoFactor of fatty acid synthesis
uses NADPH
what is the CoFactor of fatty acid oxidation
yields NADPH, can feed into electron transport chain
what is the fatty acid metabolism in the liver
Liver can receive FA from chylomicron remnants
newly synthesized fatty acids through lipogenesis
Can take fatty acids and re-esterify them and package them into VLDL and secrete them, if this system becomes overloaded then can store fat as little droplets in its own cells, fine as a temporary measure, will mobilise the fat again when don’t need it
what happens in fatty acid oxidation
linked to CoA before degradation
Need to link fatty acids back to Co enzyme A using acyl CoA synthase using up a molecule of ATP, to generate a lot more
how is acyl-CoA formed
fatty acids enter cytosol of cell, move into mitochondria
temporary shuttle, using molecule carnitine
catalyzed by CPT
Acyl CoA temporarily breaks down, fatty acid group is attached to a carnitine, transports it across mitochondrial membrane
Another Co enzyme A reattaches it to fatty acid, releasing carnitine, which can go back into cytoplasm and reused
Once in mitochondira beta-oxidation can start
what is the first stage in fatty acid oxidation
two CH2 molecules
oxidation, removal of hydrogen
generates FADH2 from FAD (energy can be fed into electron transport chain)
what is the second stage of fatty acid oxidation
add water – hydration, break double bond and add hydroxyl group to first carbon in double bond and hydrogens on second
what is the third stage of fatty acid oxidation
another oxidation
NADH2 forms from NAD (more energy that can feed into electron transport)
Broken down hydroxyl group and replaced with double bond, leading to an oxygen
Ready to release some carbons in the form of acetyl CoA
what happens in the last stage of fatty acid oxidation
release second carbon in and original carboxyl group
C=O becomes new carboxyl group and Co enzyme A comes in and joins it
produce FA that’s got two less carbons, continue till broken down whole of fatty acid, all carbons released as acetyl CoA