Lecture 11

Question 1

Fat removal

Answer 1

Fats are oily and hydrophobic therefore don’t like to mix with the cellular contents making it difficult to transport and store them without issues. Fats need to be made into an emulsion for digestion. Fats needs to be carried around the bloodstream within capsules (lipoproteins)

Question 2

Formation of emulsions

Answer 2

Using amphiphilic molecules acts as detergents and they emulsify fats into micelles

Question 3

Bile salts

Answer 3

Fats are emulsified with bile salts which are produced in the liver from cholesterol. They have polar, hydrophilic region that is variable. They are sent to and stored in gall bladder. When a meal with lots of fat is consumed, gall bladder squeezes and contracts, pushing bile salts into the small intestine where they are churned and mixed with fat. Losing bile salts through faeces is the only way to remove cholesterol. Once bile salt mixes with fats, they are reabsorbed in small intestine mucosa. Most is reabsorbed. Some is lost.

Question 4

Fat digestion

Answer 4

Fat is churned with bile salts and while in small intestine lumen, pancreatic lipase acts upon it. FAs and other products are taken up by the mucosa and converted to triglycerols.

Question 5

Gallstones

Answer 5

Common bile duct is blocked preventing bile salts from being moved into small intestine. When that happens, most fat is unable to be reabsorbed causing oily spotting, orange coloured poo and inability to control bowel movements.

Question 6

Orlistat

Answer 6

A weight loss drug prevents fat digestion causing same side effects as gallstones.

Question 7

Olestra

Answer 7

A fat substitute. It passes through the body as we cannot use it. Same properties as cooking fats. All fat soluble vitamins that would be reabsorbed with fat are no longer being absorbed. Supplemented with extra vitamins.

Question 8

Lipoproteins

Answer 8

Phospholipid monolayer with triglycerides and cholesterol in centre. Apo-protein is on external part and labels it as lipoprotein. It may act as enzyme, help cells recognise the type of fat particle is within the protein (docking receptor). Different cells will recognise different lipoproteins by the apo-proteins.

Question 9

chylomicrons

Answer 9

lowest density, biggest lipoproteins. Lots of fat and cholesterol able to be packed. Triglycerols are first packaged into chylomicrons which enter the lymph before reaching the bloodstream and finally tissue/liver.

Question 10

Packing cholesterol

Answer 10

Target cholesterol to pack into lipoproteins, they must be completely hydrophobic and so, they are esterified with FA to remove the OH which is slightly polar/hydrophilic.

Question 11

Chylomicrons in blood

Answer 11

While in circulation, they interact with the enzyme lipoprotein lipase. Which is on the capillary wall. They ‘eat’ the fat out of the chylomicrons and converts it into FAs and glycerol. If a cell needs fat, it will express lipoprotein lipase on surface. Only liver can turn glycerol to G3P therefore if they want to store the fat, they need to steal from glycolysis.

Question 12

Remnants

Answer 12

Chylomicrons with some fat digested out of them, leaving cholesterol rich remnants. Goes to liver where they will get endocytosed and liver will repack chylomicron remnants with any fat the liver made.

Question 13

Liver import/export

Answer 13

Chylomicrons remnants are repackaged with any fats and cholesterol made by the liver. They are exported back into the blood as VLDL particles.

Question 14

VLDL

Answer 14

Any cells that wants fat expresses lipoprotein lipase at capillary wall surface, digests fat and whatever is leftover goes to liver. If they take enough fat, it becomes an LDL. If a small amount is taken, it becomes an IDL. LDLs are mostly filled with cholesterol.

Question 15

Extra function of LDL

Answer 15

Having so much cholesterol relative to fat makes it a good cholesterol deliverer. Any cell that wants cholesterol expresses LDL receptor at cell surface. When LDL passes by, it is endocytosed and use cholesterol.

Question 16

Fat and cholesterol delivery steps

Answer 16

1. Fat is consumed in food
2. In small intestine, fat is churned up with bile salt to form emulsion
3. Emulsion is acted upon by pancreatic lipases in small intestine lumen which turns fat to FA and glycerol.
4. FAs and glycerol can be absorbed across the mucosa of small intestine
5. As it moves through mucosa, they are repackaged as chylomicrons.
6. Chylomicrons move through lymph to blood where cells needing fat express lipoprotein lipase that digests fats leaving a VLDL.
7. VLDL travels to liver.
8. Liver may use VLDL cholesterol for making bile salts or package cholesterol and fats made in liver as VLDLs
9. VLDLs travel in blood where cells needing fat express lipoprotein lipase and takes some fat. This forms LDLs
10. Cholesterol in LDL may be needed by cells which express LDL receptors and take cholesterol
11. Remnants return to liver for repackaging.

Question 17

Cell cholesterol dynamics

Answer 17

Nearly every cell can make it’s own cholesterol. To inhibit cholesterol production, statins can be used. They target the first enzyme in cholesterol biosynthesis which joins acetates. This enzyme is highly regulated by insulin, cholesterol levels, genes, enzyme degradation, circadian rhythms. Statins increases absorption of cholesterol in blood, decreasing [LDL]blood.

Question 18

Negative impact of LDLs

Answer 18

Decreasing blood [LDL] and increasing blood [HDL] good. In circulation, they are prone to oxidation and when they are, they become a target for macrophages. They take up ox-LDL without control becoming a foam cell. Creates an inflammatory environment that encourages plaque formation.

Question 19

HDLs

Answer 19

Produces mostly by liver. Thin phospholipid disks that travel around circulation and find any unwanted cholesterol to recycle in the liver.

Question 20

CETP

Answer 20

While HDL returns to liver, if they encounter CETP, it allows HDL to give cholesterol to VLDL. Not good as more cholesterol is retained in circulation. VLDL donates some fat to HDL which takes it back to liver. Makes no biological sense. But, when CETP is inhibited, you die.

Question 21

Ways to decrease blood cholesterol

Answer 21

Decrease cholesterol consumption

Decrease absorption from gut (phytosterols)

Decrease bile salt reabsorption

Best to inhibit HMG-CoA reductase via statins

Question 22

Cholesterol flux

Answer 22

Total cholesterol in body ~140g, ~1g cholesterol enters body via diet (0.5g absorbed)

~18g bile salts secreted into gut/day. 17.5g reabsorbed, 0.5g lost.

Decrease in intake causes increase in endogenous cholesterol synthesis. Cholesterol is important for maintaining the structural integrity of membranes and receptor/enzymatic activity.

Question 23

Membrane with saturated FAs vs unsaturated FA

Answer 23

Membrane is crystalline. Solid at room temp for saturated FA. Unsaturated FA = kinks which makes their membranes crystalline, more fluid and more permeable. Need balance between saturated and unsaturated fats for perfect permeability. Cholesterol is inserted between phospholipids to achieve balance.

Question 24

trans-fats

Answer 24

When breaking off 2C in beta oxidation, in trans fats there is a double-bond preventing the separation of alpha-C and beta-C. An enzyme shifts the double bond in the correct place before it is hydrated, O2 then beta alpha 2C chunk is broken off. Affects LDL:HDL by increasing LDL and puts you at risk of CVD. Not natural food product, makes things spreadable.