lipid metabolism

Question 1

What are some important types of lipids?

Answer 1

Triacylglycerols for fuel
Glycerophospholipids for membranes
Cholesterol for membranes
~bile salts for lipid digestion and steroid hormones for communication 
Vitamins for vision, growth etc

Question 2

What are triacylglycerols?

Answer 2

Glycerol and 3 fatty acids joined by ester bonds
Variable length
Can be saturated or unsaturated
Efficient form to store energy

Question 3

What are the sources of lipids?

Answer 3

Diet

Carbohydrates in the liver

Question 4

How are triacylglycerols digested?

Answer 4

Gall bladder secretes bile salts to emulsify it into small droplets
Lipases break it down into fatty acids and 2-monoacylglycerols
These form into micelles
Micelles are absorbed by epithelial cells (enterocytes) via passive diffusion
The fatty acids and 2-MGs can be repackaged together with apoproteins, phosholipids and cholesterol in the cells to form nascent chylomicrons

Question 5

What are chylomicrons?

Answer 5

A monolayer of phospholipids with hydrophobic tails pointing inwards to form a sphere
Cholesterol are embedded in which help to stabilise and package it all together
Free triacylglycerols are within the bundle
Apoproteins can be embedded in or sat peripherally to allow the fat to be recognised by the body

Question 6

How do micelles become chylomicrons?

Answer 6

Micelles are taken up by enterocytes
The triacylglycerols are repackaged together in the SER
Packaged proteins from the RER join the triacylglycerols
There is more processing in the golgi body
These are exocytosed from the cell into the lymphatic system to become nascent chylomicrons (as they’re not complete)
Things are added for them to become a mature chylomicron to enter the bloodstream

Question 7

What happens to the chylomicrons after they enter the bloodstream?

Answer 7

Lipoprotein lipase recognises the apoproteins
LPL chews off triacylglycerols from chylomicrons and absorbs them to be used or stored
LPL is produced by adipose, muscle and lactating mammary gland cells
LPL is regulated by insulin
Fatty acids are absorbed by cells and other remnants are taken up by the liver via receptors

Question 8

How are endogenous lipids formed?

Answer 8

Glucose is the source of carbons
Reactions occur in the cytosol
Fatty acids can be stored as triacylglycerols, oxidised as fuel, or used to make membrane components
The difference between digested triacylglycerols and endogenous lipids is that these are packaged w proteins to form VLDL (v low density)

Question 9

How are fatty acids and glycerol synthesised in the liver?

Answer 9

Glycerol is made from dihydroxyacetone phosphate which is a component from glycolysis
Citrate from the TCA cycle can be taken through a complex series of reactions to form fatty acids with glycerol and then triacylglycerols
These are packaged together w other lipids, phospholipids, cholesterol and apoproteins to form VLDLs

Question 10

What happens to VLDLs after they’re made?

Answer 10

Exactly the same as what happens to chylomicrons
However there is a cholesterol high remnant which is converted into IDL and then LDL which contains cholesterol and cholesterol esters
LDL can be returned to the liver to make more VLDL or taken up by other cells needing cholesterol to make membranes/steroid hormones

Question 11

What is fatty acid oxidation?

Answer 11

Fuel source when fasting
Long chain fatty acids are released from adipose tissue stimulated by reduced insulin and increased glucagon
These are taken up by other tissues, e.g. muscle, to produce energy
An example of a pathway is beta-oxidation

Question 12

What is beta-oxidation?

Answer 12

Fatty acids enter tissues via diffusion
They’re activated into fatty acyl CoA using ATP
These are transported to mitochondria and converted into acetyl CoA producing NADH and FADH2
This is repeated til all carbons are converted to acetyl CoA (2C)
Acetyl CoA can enter to the TCA cycle
~source of a lot of energy

Question 13

How can fatty acyl CoA be used?

Answer 13

Used for energy via the beta-oxidation or ketogenssis
Stored as triacylglycerols
Transformed into membrane components, e.g. phospholipids, sphingolipids

Question 14

Why is cholesterol important?

Answer 14

Component of cell membranes
Precursor of bile salts, steroid hormones and vitamin D
Major component of blood lipoproteins e.g. Chylomicrons, VLDL

Question 15

How is cholesterol absorbed?

Answer 15

Enters enterocytes via diffusion
It can’t be fully metabolised so must be regulated by excreting it
Enterocytes can transport excess back into the gut lumen or lose it in the form of bile salts
This can by excreted in faeces
~defects in protein transporting cholesterol out of enterocytes can lead to high cholesterol and CVD

Question 16

How is cholesterol synthesised?

Answer 16

Occurs in cytosol in the liver
Regulated via cholesterol, glucagon and cholesterol lowering drugs to inhibit HMG-CoA reductase and by insulin to activate it
1. Acetyl-CoA is turned into Mevalonate via the activation of HMG-CoA
2. Mevalonate—>Isoprenes
3. Isoprenes(5C)—>Squalene(30C)
4. Squalene—>Cholesterol

Question 17

How do statins combat high cholesterol in blood?

Answer 17

It competitively inhibits HMG Co-reductase

Statins have a higher affinity to bind

Question 18

What happens to cholesterol after it’s secreted by the liver?

Answer 18

Becomes bile salts
~stored in goal bladder, secreted into gut or emulsifies fat
Becomes biliary cholesterol
~secreted into gut or reabsorbed
Becomes cholesterol esters
~packaged in VLDL and transported

Question 19

Why are bile salts useful in the gut in terms of bacteria?

Answer 19

Bacteria uses and modifies them via reconjugation so they are recycled to the liver
Bile salts are charged molecules which aids its transportation and ability to retrieve fats

Question 20

How does cholesterol enter cells?

Answer 20

LDL are endocytosed by LDL receptors
These recognise the apoproteins on the lipoprotein surface
Excess LDL can be endocytosed by macrophages to form a foam macrophages that can sit in the wall of a blood vessel
~inflammation and contribution to atherosclerosis