7 lipids and biological membrane 2 Flashcards
What are 3 sources cells can obtain fatty acid?
- fats consummed in diet
- fats stored in cells as lipid droplets
- fats synthesised in one organ and transported to another
At organism level, where do vertebrates obtain fats from?
- diet
- mobilising fat stored in specialised tissues and in the liver
- converting excess dietary carbs to fats for export to other tissues
what is an important source of dietary calories?
fats 30-40% of calories in american diet are from fat - high fat diet
How can fats be digested?
through emulsification
what is the process of emulsification?
- bile acids are added to fat droplets in duodenum
- bile acids emulsify fats into mixed micelles containing bile salts and triacylglycerols
What does micelle formation increase?
increases the fraction of lipid molecules accessible to the action of water-soluble lipases
what digests triacylglycerol?
pancreatic lipase
What does pancreatic lipase triacylglycerol into?
**2 fatty acid **and 1 monoacylglycerol
before its glycerol backbone with 3 FA chains
enzyme cleaves off 2 FA
What parts of fats are absorbed into the small intestine?
monoacylglycerols and fatty acids by villi
What happens once fatty acids and monoacylglycerols are absorbed into the small intestine via villi?
re-assembled into triacylglycerol (same as triacylglycerol)
then packed into particles called chylomicrons and enters the lymphatic system
What does the lymphatic system do?
help transport fat to other organ
How are triacylglycerol packed before entering the lymphatic system?
chylomicrons
what are chylomicrons
a class of lipoproteins particles made up of lipids and apoliproproteins
What are apoliproproteins?
lipid-binding proteins responsible for the transport of triacylglycerol an dothers
combines with lipids to form diff class of lipoprotein particles
what happens to chylomicron?
- carried to fat tissues and muscles via lymphatic system
- in the capillaries of the tissues, the triacylglycerol in the chylomicron are hydrolyzed by lipoprotein lipase into fatty acids and glycerol
In fat tissues
* FA and glycerol are re-esterified to triacylglycerol for storage
In muscles
* the FA are oxidised for energy
* the remnents of the chylomicron will go to liver and taken up by endocytosis
Do ingested fats first go to the liver?
never
Where are the enzymes of FA oxidation located?
mitochondrial matrix
How to fatty acids enter the mitochondria to get oxidised?
FA with 12 or less carbons can enter directly
14C or more carbons (majority of FA) need help from membrane transporters cuz of hydrophobicity
What are the 3 stages of FA degradation?
- activation of FA in cytosol
- transport of FA into the mitochondria via carnitine shuttle
- β-oxidation in the mitochondrial matrix
FA with 12 or less carbons skip step 2
What happens in stage 1 of FA degradation?
activation of FA in the cytosol
* acyl-CoA synthetase isozymes activate FA to produce fatty acyl CoA
What is step 2 of FA degredation?
carnitine shuttle (for 14C or more) into the mitochondria
* Fatty acyl CoA attached to carnitine to form fatty acyl-carnitine
* transport into the matrix from the cytosol
Fatty acyl CoA + carnitine = fatty acyl-carnitine
once bind, commits the fatty acyl group to the oxidative fate
What is the rate-limiting step for the oxidatino of FA in mitochondria?
the carnitine-mediated entry process
What is stage 3 of fatty acid degradation?
Fatty acid oxidation
* occurs in mitchondria
* even-numbered FA are broken down by β-oxidation and acetyl CoA is released
* β-carbon is attacked during the oxidation process
3 stages
1. β-oxidation
* remove 2C (acetyl CoA) from the carboxyl end of the FA chain
* produce NADH and FADH2
2. acetyl groups of the acetyl coA are oxidised to CO2 in the kreb cycle
3. NADH and FADH2 produced in steps before donate electrons to the ETC to produce ATP
energy released by FA oxidation is also conserved as ATP
How many steps per round in stage 3 of FA degradation (βoxidation of FA)?
4 steps per round
What do we get from each round of β-oxidation?
- 1 molecules of acetyl CoA
- 1 molecule of NADH
- 1 molecule of FADH2
produce one more acetyl CoA as the last acetyl group from the final oxidation cycle, at final round, we snip 4C FA chain into 2 2 carbon chain
How many acetyl CoA, NADH, and FADH2 will β-oxidation of a Cn fatty acid produce?
n/2 molecules of acetyl CoA
n/2-1 molecules of NADH
n/2-1 molecules of FADH2
What is the fates of acetyl-CoA produced from the oxidation of FA?
enters the citric acid cycle and is oxidised to CO2 and H2O
Can unsaturated fatty acids go through the 3 steps of FA oxidation?
no the process was good for saturated FA
unsat they have double bonds and enzymes cant on it
When does oxidation of FA occur?
only when need energy and theres no glucose left
in the liver, what 2 paths can the fatty acyl-coA formed in the cytosol undergo? What determines which is taken?
- β oxidation by enzymes in mitochondria
- conversion to triacylglycerol and phospholipids by enzyme in cytosol
pathway depends on the rate of transfer of long chain fatty acids into mitochondria
what happens when the liver is supplied with glucose as fuel?
the action of carnitine acyltransferase I is inhibited
so oxidation of fatty acid is inhibited
How can fatty acids be synthesised?
condensatino of 2C acetyl CoA units form long hydrocarbon chains
where does the biosynthesis of fatty acids occur?
in the cytosol of
* liver cells
* adipocytes
* mammary glands (during lactation)
Compare the site of reaction for biosynthesis and degradation of FA and glucose?
biosynthesis = cytosol
degredation = mitochondria
can control the direction of making and breaking molecules
glucose is in the same compartment but uses diff enzyme and pathway
What is the electron-carrier for anabolic processes?
NADPH
In cytosol of liver cells, what is there a high conc of?
NADPH and NADP+
providing strong reducing enviornment for synthesis of FA and other biomolecules
In liver and fat cells, where is NADPH mainly generated by?
pentose phosphate pathway and malic enzyme
Where does the acetyl CoA used in fatty acid synthesis from?
from pyruvate oxidation in the mitochondria
How is fatty acids synthesized from the conversion of glucose to acetyl coA?
- glucose is converted to pyruvate via glycolysis
- pyruvate enters the mitochondria and is converted to acetyl coA by pyruvate dehydrogenase and oxaloacetate (OAA) by pyruvate carboxylase
- acetyl coA and OAA are condensed to form citrate
- citrate crosses the mitochondrial membrane back out to the cytosol
- critrate is then cleaved back into OAA and acetyl coA by ATP citrate lysase
- acetyl CoA is used for fatty acid synthesis
How is acetyl coA converted to Malonyl coA during biosynthesis of FA?
- formation of malonyl CoA is an irreversible process (commited step)
- rxn catalysed by acetyl-CoA carboxylase
acetyl coA + carboxyl group (from bicarbonate) + acetyl-coA carboxylase = malonyl coA
uses one ATP in the process
What is the overall goal to acheive biosynthesis of FA?
- attach acetate unit (2-carbon) from malonyl-CoA to a growing chain
- all reactions are catalysed by a multienzyme complex, fatty acid synthase (FAS)
- prep: malonyl CoA and acetyl CoA (as the start acyl group or longer fatty acyl chain) are bound to FAS and lose CoA
How are the long carbon chain of FA assembled?
in a 4 step sequence
* condensation
* reduction
* dehydration
* reduction
CRDR - call renee dr
What is formed at the end of th 4 step sequence (assembling of the long carbon chain of FA)? What happens to it?
saturated acyl group
it undergoes condensation reaction with malonyl-group
the malonyl group is bound to the acyl carrier protein (ACP) of FAS
what happens with each passage through the cycle of assembling the long carbon chain of fatty acid?
the fatty acyl chain is elongated by 2 carbons
How is NADPH used in this 4 step sequence for assembling the long carbon chain of FA?
it is used as the reducing agent
in the reduction steps
CRDR
How does the fatty acyl chain grow?
by 2C units by the activated malonate, removing the 3rd carbon as CO2 in the process
When does the growth of the chain elongation stop?
after 7 cycles of condensation and reduction, a 16C palmitoyl group is produced
and chain elongation stops (dk why)
the free palmitate is then released by a hydrolytic activity
released as free FA
How are palmitate form?
by repeating the fatty acid synthase reactions for 7 cycles
after 7 cycles of condensation and reduction = a 16C palmitoyl group is produced
Summary of synthesising palmitate (16C) from acetyl coA
Compare Fatty acid breakdown vs synthesis
- where
- add/remove what
- role of acetyl CoA
- oxidative vs reductive process
- NAD/FAD/NADPH
- what are FAs bound to
- how many enzymes
when a cell/organism have more than enough metabolic fuel to meet its energy needs, what happens to the excess?
converted to FA and stored as lipids
What is the rate limiting step of FA synthesis?
the rxn of converting acetyl CoA to malonyl CoA
with palmitoyl-coA as a feedback inhibitor of the enzyme
inhibits acetyl-CoA carboxylase that adds carboxyl to acetyl-coA and turning it into malonyl coA
How is citrate a point of control in FA synthesis?
when conc of acetyl coA and ATP increase in mitochondria, citrate is transported out and becomes the precursor of cytosolic acetyl-CoA and activator of malonyl coA production
what are the hormonal control of FA synthesis?
Glucagon and epinephrine triggers phosphorylation of the enzyme and stops malonyl coA production
What is palmitate a precursor for?
- other long chain fatty acid
- two most common monosaturated fatty acids (palmitoleate and oleate)
Why can mammals convert oleate to linoleate?
its an essential fatty acid
cant be synthesized so need to get in diet
what can animals do for fuel storage?
synthesize and store large quantities of triglycerise as fuel storage
the entire process of triacylglycerol biosynethesis
glycerol-3-phosphate and fatty acyl CoA serves as precursors for the synthesis of triacylglycerol
glycerol 3 phosphate is formed from:
* dihydroxylacetone phosphate (DHAP) from glycolysis or
* glycerolneogenesis in adipose tissues (abrev vers of gluconeogenesis followed by conversion of DHAP to glycerol-3-phosphate
the first stage of biosynthesis of triacylglycerol
1. acylation of the 2 free hydroxyl groups of glycerol 3 phosphate by 2 molecules of fatty acyl coA to form diacylglycerol 3 phosphate or phosphatidic acid
2. phosphatidic acid can be converted to form triacylglycerol or glycerolphospholipids
3. phosphatidic acid is then hydrolyzed to form diacylglycerol by phosphatidic acid phosphatase
4. transesterification with the third fatty acyl CoA would yield triacylglycerol
What is the general process of biosynthesis of triacylglycerol?
- formation of glycerol 3 phosphate
- formation of phosphatidic acid from glycerol 3 phosphate and fatty acyl coA
- phosphatidic acid hydrolyzed and transesterified to triacylglycerol
How is triacylglycerol synthesis regulated by insulin?
- in humans, the amount of body fat stays relatively constant over long periods
- excess carbs, fat or protein consumed is stored in the form of triacylglycerol
- biosynthesis and degradation are regulated such that the favoured path dependson the metabolic resources and requirements at the moment
- insulin promotes the conversion of carbs to triacylglycerol
Insulin can enhance conversion to acetyl coA and fatty acid formation
In the absence of insulin (as in diabetes), the synthesis of ketone bodies is increased due to elevated levels of fatty acids and acetyl-CoA, as the body shifts towards fat utilization for energy rather than glucose.
what is the triacylgylcerol cycle?
- ~75% of all FA released by lipolysis are converted back to triacylglycerols rather than used for fuel
- some of this FA takes place in the adipose tissue
some takes place via the triacylglycerol cycle
* free FA are transported to the liver, made into triacylglycerol
* triacylglycerol are exported to blood stream
* taken up again by adipose tissue after release by lipoprotein lipase
- flux through this cycle is low when other fuels are available as fuel and when the release of FA from fat cells are limited
Where does the phospholipid synthesis occur primarily?
surface of the smooth ER
What 4 things does the assembly of phospholipids requires?
- synthesis of the backbone molecule (glycerol or sphingosine)
- attachment of the FA to the backbone
- addition of the hydrophillic head group via phosphodiester linkage
- alteration or exchange of the head group to yield the final product
What is the first step of biosynthesis of glycerolphospholipids?
is shared with the pathway to triacylglycerols, forming phosphatidic acid
How can cholesterol be obtained?
from diet or synthesized in body
How much cholesterol does an adult on low-cholesterol diet synthesis per day?
800mg
where is cholesterol mostly synthesised?
in the liver, although intestine can as well
what is cholesterol made from?
acetyl-coA
what can be made if we have acetyl coA?
fatty acids and cholesterol
How are lipids transported in the blood stream?
as lipoproteins
why are there different variants of lipoproteins?
for different functions and different protein and lipid composition
What do chylomicrons do?
transports dietary triacylglycerol from small intestine to other tissues via lymphatic system
What are VLDL? What do they do after a meal and during fasting?
very low density lipoprotein
* transport lipids from diet to adipose tissue for storage after a meal
* during fasting, VLDL transports lipids from liver to muscles (use fat for energy)
What is LDL?
low density lipoprotein
what is the major carrier of cholesterol in the blood?
LDL
Where does LDL transport cholesterol to?
from liver to peripheral tissues such as muscles, adrenal glands and adipose and regulate cholesterol syntehsis at those sites
What does HDL do?
a shuttle that moves cholesterol through out the body
* they binds and esterifies cholesterol released from peripheral tissues and transfers cholesterol esters to the liver or other tissues where cholesterol is used to make steroid hormones
which is good or bad: LDL HDL, why
LDL is bad
HDL is good
excess cholesterol is the form of LDL
normal ratio should be LDL/HDL 3:5
Why is LDL sometimes called bad cholesterol and HDL is good?
LDL - transport cholesterol throughout our body, high levels can lead to build up of cholesterol in our arteries
HDL - transports cholesterol from peripheral organs back to liver
