W5 - Fat Metabolism Flashcards
What are fats usually carried in around the body because they have detergent like properties?
lipoproteins
What are simple lipids
Lipids composed of only FAs, glycerols + alcohols
What are complex lipids
Lipids that contain FAs, glycerols + other groups
What do lipoproteins carry?
TAGs
Cholesterol
Which parts of a lipoprotein are hydrophilic + which are hydrophobic?
Hydrophilic shell
Hydrophobic core
What does the outer layer of a lipoprotein contain?
Monophospholipids
Cholesterol
Protein
There are 4 main lipoproteins in the human body.
What do they carry?
2 are main carries of TAG
2 of cholesterol esters
List the 4 main lipoproteins
Chylomicrons
VLDL (Very low density lipoproteins)
LDL
HDL
HDL or LDL for chylomicrons
ULDL (ultaLDL)
Which is the biggest lipoprotein?
Chylomicrons
What does the chylomicron carry?
90% TAG
Some Cholesterol esters (CE)
% of protein + lipids in chylomicrons
High or low?
Protein = lowest %
Lipids = highest %
Where are chylomicrons made?
Small intestine
What do VLDLs carry?
TAG
Cholesterol esters
Where are VLDLs made?
Liver
What do LDLs carry?
ONLY cholesterol esters
LDLs - considered bad cholesterol
What do HDLs carry?
ONLY cholesterol esters
HDLs - considered good cholesterol
Which lipoprotein has the highest % of protein?
HDL
What are probably the strongest lipid predictor for CV disease?
HDLs
Higher content in blood = ⬇️ risk of CV disease
Quick overview of the consumption + absorption of fats
TAGs broken down by lipase
Packaged into myocells
Transferred into epithelial
Synthesised by chylomicrons
Into lacteal which drains into lymph, then blood + subclavian vein.
== Chylomicrons in circulation
Fat absorption has happened in the postprandial state.
Want to store the fat.
Where do the chylomicrons travel to?
Then what happens?
Extra hepatic tissues
Bv here have LPL on their walls.
= Chylomicrons dock onto this enzyme to be broken so the TAGs can be broken down to release FAs + glycerol.
FAs enter tissues.
Repackaged into TAGs + stored.
What is the chylomicron called once it has lost most of its TAGs when docked onto the lipoprotein lipase in bv walls?
Chylomicron/lipoprotein remnant
Where is the Chylomicron/lipoprotein remnant transported to
Liver
What happens to the Chylomicron/lipoprotein remnant in the liver?
Broken down + reutilised.
What happens to the cholesterol of the Chylomicron/lipoprotein remnant once it has been broken down + reutilised in the liver?
Joins a pool of cholesterol in the liver where has many functions.
1 of which = Bile created
Can also be packaged into LDL to take cholesterol to the other bodys tissues.
How can more cholesterol enter bloodstream?
Low HDL levels
High LDL
What does the liver do with the fat it contains?
Packages it into VLDL
VLDL sent to peripheral tissues so they can store the TAG.
What are the 4 ways of regulating FA utilisation?
Lipolysis of TAG to form FFAs
Re-esterification of FAs or mobilisation from adipose tissue
Transport of ACoA into mit
Availability of FAD + NAD for b-oxidation
In what states can adipocytes in adipose tissue be used?
Post absorptive states + exercise
How is HSL (hormone sensitive lipase) regulated?
By phosphorylation.
What enzyme converts the inactive form of HSL to its active form and how?
Protein kinase
By adding a phosphate group.
What stimulates protein kinase to convert inactive HSL to active HSL?
Ca2+
Adrenaline
= Both i.e from exercise
Growth hormone cortisol (i.e from stress)
When wouldn’t you want HSL in its active form?
Just after eating
Enzyme to convert HSL in its active form to HSL in its inactive form?
Phosphatase
What stimulates phosphatase to convert HSL in its active form to HSL in its inactive form?
Insulin
Why is it difficult to get FAs out of the adipocytes?
Due to re-esterification
Does the glycerol in the adipocyte need to go or can it stay?
Needs to go.
Can’t be reused to make TAG.
How is a fatty acyl-CoA converted back into TG?
By reesterification + the addition of a-glycerol-P
What happens to lipolysis with exercise?
⬆️
What is FA transport across cell membranes dependent on?
Plasma FA conc
What are the functional protein carriers allowing FA transport across cell membranes?
FABP (FA binding protein)
FAT/CD36 (FA translocase)
FATP (FA transport protein)
What happens to the FA once inside the cell?
Becomes fatty-acyl-CoA by Acyl-CoA synthethase enzymes.
Where can the FAs come from when moving from the blood into the interstitial fluid?
Chylomicron
VLDL
Albumin
How do FAs move from the interstitial fluid into the sarcoplasm of a muscle cell?
⬇️ conc grad through FAT/CD36.
What happens to the Fatty-acyl-CoAs in the cell?
Can either:
- be incorporated into lipid pools
OR
- be oxidised by mit for energy
Give an example of a lipid pool in muscles
IMTG droplets
Intramuscular TG
Lipolysis of IMTG, by what enzyme?
Active form of HSL
What is protein kinase stimulated when converting inactive form of HSL to active form for the lipolysis of IMTG?
Ca2+
Adrenaline
AMP
Membranes of the mitochondria in regards to lipid permeability
Outer - permeable to lipids
Inner - IMpermerable to lipids
Where is the CPT 1 located in the mitochondria?
Outer membrane
What does CPT 1 do in the carnitine shuttle?
Attaches carnitine group to acyl-CoA
removes CoA from acyl-CoA
== Acyl-carnitine
What in the mitochondria helps acyl-carnitine move across the inner membrane into the mit matrix?
CACT (Carnitine acyl carnitine translocase)
What must happen once the acyl-carnitine has entered the mit matrix?
How does this happen?
Need to remove carnitine group
Put CoA back on
== By CPT2
=== AcylCoA now ready in mitochondrial matrix
What happens to the AcylCoA once in the mit matrix?
Undergoes b-oxidation
What are the later forms of Acyl CoA as it goes through the b-oxidation cycle in the matrix of the mitochondria before entering the TCA cycle as Acetyl-CoA (ACoA)?
Acyl CoA
2-trans-enoyl CoA
L-3-hydroxyl acyl CoA
3-ketoacyl coA
Which is the rate limiting enzyme in the b-oxidation cycle in the matrix of the mitochondria for Acyl-CoA
3rd enzyme = Beta hydroxy Acyl CoA dehydrogenase (beta HAD)
What happens to plasma FA conc during prolonged exercise?
⬆️ after an initial drop
Why is there an initial drop in plasma FA during prolonged exercise when looking at a graph?
Slow FA mobilisation from adipose tissue
Uptake of FA from working muscles straight away
Why does plasma FA conc increase during prolonged exercise?
Insulin is red. so less glucose in blood
Adrenaline is increased.
Glycerol stores may be depleted.
== ⬆️ HSL = ⬆️ lipolysis = ⬆️ FA in blood
What does increase FA in plasma result in during exercise?
Greater flux = drives a FA oxidation increase
What does an increased FA flux into plasma do to CHO?
⬆️ acetyl-CoA = inhibits PDH + PFK, ⬆️ citrate accumulation
== G-6-P accumulates = glycogenolysis inhibited = ⬇️ con grad for glucose uptake
== ⬇️ CHO oxidation
Which of LDL + HDL has a longer half-life ?
LDL
Lasts 1.5-2 days
How long do chylomicrons VLDLs last in the body?
Few hours
What does damage to the LDL enable?
⬆️ its affinity to bind to a receptor on macrophages.
Taken into macrophage,
How can LDLs be damaged?
Toxins
Free radicals
High glucose
Do macrophages have cholesterol sensors?
No
What does it mean that macrophages don’t have cholesterol sensors?
They keep taking in LDLs
== Changed into a foam cell (bigger than a macrophage)
Can foam cells penetrate bv walls?
yes
What can an accumulation of foam cells on vessel walls cause?
Inflammation which can lead to fatty streaks. –> Atherosclerosis
What can HDL do in regards to the foam cells?
Can dock onto its receptor + remove the excess cholesterol.
Takes cholesterol to liver where used for bile acids
Monounsaturated fats have how many double bonds
1
After FAs have been released from fat cells, what is the name of the protein carrier that transports them in blood?
Albumin
What is lipolysis NOT stimulated by?
Insulin
How are long chain fatty acids transported from the small intestine through the body?
In chylomicrons
Transport of fatty acids across the inner mitochondrial membrane is dependent upon…
Carnitine
What is involved in the transport of short chain fatty acids around the blood
Albumin
Increased glycogenolysis in exercise is likely due to…
Increased AMP
What will inhibition of PFK do to CHO oxidation + glycolysis?
Inhibits it
What effect will a reduction in FAD have on flux through beta oxidation?
Reduce it
