Topic 2: Lipid transport, structure, and metabolism Flashcards
Classifications of lipids (5)
Fatty Acid Glyceryl esters Sphingolipids Sterol derivitives Terpenes
Triglycerol structure
glycerol backbone
3 fatty acids
Types of phospholipids
2
Glycerophospolipids
Sphingolipids
glycerophospholipid structure
glycerol backbone
2x fatty acid
PO4-alcohol
Sphingolipid structure (2 types)
sphingosine backbone
fatty acid
(phospholipid version)
PO4-Choline
(glycolipid version)
Mono or oligosaccharide
types of glycolipids (2)
sphingolipids
galactolipids (sulpholipids)
galactolipid (sulpholipid) structure
glycerol backbone
2x fatty acid
mono or disaccharide-SO4
X group of phosphaditic acid (PA)
-H
X group of phosphaditylethanolamine (PA)
ethanolamine
-CH2CH2NH3+
X group of phosphatidylcholine (PC)
Choline
-CH2CH2N+(CH3)3
X group of phosphaditylserine (PS)
serine
-CH2CH(COO-)NH3+
X group of phosphatidylglycerol (PG)
glycerol
-CH2CH(OH)CH2OH
X group of phosphatidylinositol (PI)
myo-inositol 4,5 biphosphate
how to make sphingosine
attach a ser backbone and fatty acid (palmatate) to glycerol
X group of sphingomylein
phosphocholine
PO3CH2CH2N(CH3)3
X group of glucosylcerebrocyde
a sphingolipid
glucose
X group of lactosylceramide
a sphingolipid, (globoside)
di or trisaccharide
X group of ganglioside GM2
a sphingolipid
complex oligosaccharide
Double bonds and carbon length of palmitate
C16, 0 double bonds
Double bonds and carbon length of stearate
C18
0 double bonds
Double bonds and carbon length of oleate
C18
1 double bond
Double bonds and carbon length of linolate
C18
2 double bond
Double bonds and carbon length of linolenate
C18
3 double bonds
Linolate vs linolnate
Linolate has 2 double bonds
Linolenate has 3 double bonds
Both are C18 fatty acids
Double bonds and carbon length of arachidonate
C20
4 double bonds
Why is olestra not accessible by gut enzymes ?
The glucose backbone is not accessible by the enzymes.
2 medical problems associated with olestra
1) loss of fat soluble vitamins (ADEK)
2) olestra is not absorbed and therefore egested, leading to anal leakage
WHAT DID THE DEVELOPMENT OF THE FAT SUBSTITUTE OLESTRA REINFORCE IN OUR KNOWLEDGE ABOUT THE
A) SPECIFICITY B) EFFICIENCY OF PANCREATIC LIPASE ENZYMES?
Enzymes are rather specific to which backbones are accessible to them
Lipids are typically fully absorbed
WHAT ARE THE IMPLICATIONS OF THIS KNOWLEDGE (re: olestra) FOR NORMAL DIETARY LIPID ABSORPTION & ENERGY UTILISATION?
Lipids are typically absorbed and fully digested.
2 important fatty acids for infant development
linolate and linolenate
Common type of double bond in lipids
cis bonds
Cis double bonds create a ___ degree kink in the fatty acidq
30 degree
How to make a helical fatty acid
add a double bond every 3 carbons
eg docosahexaenoic acid (DHA)
main component of retinal membrane phospholipids
50% docosahexaenoic acid (DHA)
Found mostly in the myelin sheath
preferred form of fatty acid to store energy
saturated
fatty acid form preferred for position 2 of phospholipids
unsaturated
IF I FED YOU A LABORATORY DIET
RICH IN EITHER SATURATED OR UNSATURATED FATTY ACIDS, WOULD YOUR BODY
COMPOSITION CHANGE AND IF SO, HOW?
Fat depots would reflect dietary intake, but membranes would not
Membranes are controlled for fluidity
What is the limit to adding double bonds to fatty acids?
cannot add past C9
oleic acid structure
ω9
18:1 Δ9
linoleic acid structure
ω6
18:2 Δ9,12
linolenic acid structure
ω3
18:3 Δ9,12,15
how to get eggs to have omega 3 fatty acids
feed them flax
Where can enzymes insert double bonds in fatty acids?
they use 6-desaturase and 5 desaturase to insert between C-4 and C-9
HOW DO WE GET FROM 18:2 Δ9,12 TO 22:5 Δ4,7,10,13,16 ?
You can add a 4 double bond with 6 desaturase and then beta oxidise
HOW DO WE GET FROM 18:3 Δ9,12,15 TO 22:6 Δ4,7,10,13,16,19 (DHA)?
6 desaturase extend (add 2C) 5 desaturase extend extend 6 desaturase beta oxidationq
Lipoprotein that transports dietary fatty acids
chylomicrons
3 types of lipases
Pancreatic
for digestion of dietary fat
Bloodstream
eg lipoprotein lipases
Hormone sensitive
in adiocytes for mobilizing fat stores
Emulsifying agent for dietary lipids
bile salts
amphoteric
Role of colipase on lipase
Colipase binds to lipase and opens the ‘lid’ exposing the active site
what is a micelle ?
A monolayer of bile salts filled with triglycerides
4 types of lipoproteins
clylomicrons
VLDL
LDL
HDL
Chylomicron density
<1.006 g/mL
VLDL density
0.95-1.006 g/ml
LDL density
1.006-1.063 g/ml
HDL density
1.063 - 1.210 g/ml
why is LDL associated with high cholesterol ?
Lots of cholesterol is used in the membrane of LDL
key coenzyme in chylomicron for lipoprotein lipase regocnition
apo-CII
where would you find a apo-CII ?
It is a coenzyme found on the surface of a chylomicron and VLDL
Difference between cholesterol and cholesteryl ester
cholesterol is amphipathic and will stay in the membrane
cholesteryl esters are entirely hydrophobic and will enter the centre of a chylomicron
Locations of liporotein lipase
Peripheral tissues, adipose, muscle
3 types of hormone sensing lipases
Adipocyte triacylglycerol lipase (ATGL)
TG-> FA + DG
Hormone sensitive lipase (HSL)
DG -> FA + MG
Monoacyl glycerol lipase (MGL)
MG -> FA + Glycerol
regulation of hormone sensitive lipases is controlled by
glucose
cAMP / protein Kinase A mediated events
why lipid is slow energy release
hydrophobic environment
enzymes can only get at the fat from the outside of adipocyte
Hormones that trigger triclycerol breakdown (2)
glucagon
epinepherine
WHAT IS THE METABOLIC FATE OF A FATTY ACID TAKEN IN AS PART OF THE DIET?
It will be digested and stored in the adipose tissue.
It may be used for energy or building blocks
WHAT WOULD HAPPEN IF YOU INGESTED A PANCREATIC LIPASE INHIBITOR WITH YOUR BIG MAC?
It would inhibit the breakdown of dietary fats in the small intestine, and therefore inhibit absorption.
Why is there a low free fatty acid content in the blood ?
The carboxyl end is rather reactive
Can a fatty acid leave the mitochondrion ?
No. Once it enters, it cannot be exported
bond between coenzyme A and fatty acid
thioester
(-SH + HOOC-R
This enzyme attaches fatty acids to coA
thiokinase
2 procedures driven by pyrophosphate breakdown
Fatty acid -> fatty acyl CoA
UDP glucose production
Non covalently bound forms of fatty acid (2)
Albumin (blood) - has 7FA max
Fatty acid binding protein - clamshell
3 parts of carnitine transport system
Carnitine AcylTransferase-I
Carnitine Transporter
Carnitine AcylTransferase-II
6 steps of carnitine transport system
Thiokinase generates fatty acyl CoA in cytosol
Carnitine AcylTransferase-I
Attaches fatty acid from Fatty acyl CoA to carnitine
Pores (create by porin) in outer mitochondrial matrix allows fattyl adducts to pass into intermitochondrial space
Carnitine Transporter
Transport fattyAcyl carnitine across inner mitochondrial membrane
Exchanges it with free carnitine (antiport)
Carnitine AcylTransferase-II
Reattaches fatty acid to CoA-SH
Beta oxidation
Permeability of mitochondrial membranes
the inner mitochondrial membrane is basically impermeable, but the outer is quite leaky
Fatty acids carried by carnitine
long chain (C16 - C22)
Carnitine derived from these amino acids
Lysine and methionine
WHICH OF THE VARIOUS FATTY ACID FORMS THAT YOU HAVE LEARNED ABOUT INVOLVE COVALENT LINKAGES: CARNITINE, FATTY ACYL CoA , FABP, CHOLESTERYL ESTER, TRIGLYCERIDE, ALBUMIN?
CARNITINE, FATTY ACYL CoA, CHOLESTERYL ESTER, TRIGLYCERIDE
FABP (fatty acid binding protein) and albumin are the only ones that do not
WHY DOES THE CELL NEED A FATTY ACID TRANSPORTER IN THE PLASMA MEMBRANE?
To allow fast and specific transport
WHY ARE CARNITINE-DEFICIENT PATIENTS TREATED WITH MEDIUM CHAIN FATTY ACIDS?
carnitine transports long chain fatty acids, which a carnitine patient wouldn’t be able to handle.
Medium chain FAs use a different pathway.
4 steps to beta oxidation
oxidation
hydration
oxidation
clevage
Where does the energy come from in beta oxidation ?
the 2 oxidation steps produce reducing agents
(FADH2 and then NADH)
Acetyl coA is a product, which is fed into the TCA cycle
what is produced by beta oxidation ?
Acetyl co A (2 carbons) and a shorter fatty acid
How many water molecules come from one palmatate molecule ?
It produces 23, but one is required to remove it from the glycerol backbone
Where is usable water produced in beta oxidation ?
Electron transport chain
Regulation of beta oxidation
1) Substrate supply (main mechanism)
2) NADH inhibits 3-OH-CoA dehydrogenase (3rd step)
3) Acetyl CoA inhibits thiolase (3rd step)
main difference between mitochondrial and peroxisomal beta oxidation
Aside from location : mitochondria vs peroxisome (glyoxisome in plants) ,
the FADH2 and NADH in peroxisomal β oxidation is recycled without electron transport chain.
What does ω-oxidation do?
Adds a carboxyl group on the omega end of a fatty acid so you can do beta oxidation from both sides
Makes adipate and/or succinate
WHERE IS THE “USEABLE” WATER GENERATED IN THE β-OXIDATION OF FATTY ACIDS?
Electron transport chain
COMPARE (2.5 MARKS) AND CONTRAST (2.5 MARKS) : FATTY ACID MITOCHONDRIAL β-OXIDATION, PEROXISOMAL β-OXIDATION & ω (OMEGA)-OXIDATION.
Aside from location : mitochondria vs peroxisome (glyoxisome in plants) ,
the FADH2 and NADH in peroxisomal β oxidation is recycled without electron transport chain.
omega oxidation takes place in the mitochondria, but adds a carboxyl group to the omega end without affecting the length
WHAT IS SIGNIFICANT ABOUT THE ENTRY OF FATTY ACYL CoA INTO THE MITOCHONDRIAL MATRIX?
Once its in, its only fate is beta oxidation
If in the liver, it may undergo ketogenesis
In well fed liver, what are the sources of acetyl coA and oxaloacetate ?
Acetyl CoA comes from fat, and the oxaloacetate is formed from pyruvaate
In starving liver, where does oxaloacatate come from ?
Gluconeogenic precursors are mobilized to create pyruvate and oxaloacetate.
Adipose tissue is broken down to acetyl coA
Beta oxidation releases some energy, so TCA is not necessary.
Where does the glucose come from during starvation ?
When glycogen stores are used up, anapleurotic steps are taken to produce oxaloacetate.
Oxaloacetate is then exported to make glucose
Where to the ketone bodies come from during starvation ?
Fat deposits are broken down into Acetyl CoA
The Acetyl CoA is then used to make ketones
How is the TCA cycle affected in the liver during starvation ?
It is shut down completely
All gluconeogenic precursors are used to make oxaloacetate, then glucose
Acetyl CoA from fat is used to make ketones
The liver gets all the energy it needs from beta oxidation
Ketone bodies formed by the liver
Acetoacetate
D-β hydroxybutyrate
acetone*
*not used for energy (its a waste product)
What tissues use ketones ?
In starvation, most tissues other than the liver (where it was made) will use ketones
Where are ketones produced ?
The mitochondria of the liver
When are ketones produced ?
Ketones are always being produced, but it happens especially during starvation
Why can liver not use ketones ?
It does not have the 3-ketoacyl CoA transferase
Why are ketones not prominent always ?
Ketones are acidic and will cause acidosis or death
WHY DOES THE MYOPATHIC (MUSCLE-ONLY) TYPE HAVE NORMAL KETOGENESIS BUT FAT(TY ACID) ACCUMULATION IN MUSCLE?
Ketones are produced in the liver
Disabling fat transport in the muscle would not affect ketogenesis
WHERE DOES THE STARVING LIVER GET ITS ENERGY?
The oxidizing steps of beta oxidation produce reducing agents for the electron transport chain
WHY DOES THE BRAIN ADAPT TO USING KETONE BODIES DURING STARVATION NOT USE FATTY ACIDS?
ketones are smaller than fatty acids and polar
They can therefore cross the blood brain barrier
