Lipids Flashcards
Discuss the process of fat absorption
- Large triglyceride droplets are obtained from the diet
- They are then emulsified by bile salts in the intestine into smaller lipid particles = increase SA = greater area for enzymes to work e.g. pancreatic lipase- breaks down into monoglycerides and free fatty acids
- These can then enter the epithelial cells of the small intestine from the lumen in micelles (incorporation into micelles is facilitated by bile salts)
- Here they reform into triglycerides (monoglycerides and fatty acids recombine)
- They then aggregate and become coated with lipoproteins = form chylomicrons
- Chylomicrons can travel through lacteals (the lymphatic vessels of the small intestine which absorb digested fats) and into the bloodstream
What are lipoproteins?
Lipids and protein complexes that are needed to transport lipids around the body
As lipids are hydrophobic- can’t travel in the blood, so need a hydrophilic coating = protein
more lipid = less dense
more protein = more dense
What are the 5 classes of lipoproteins?
- Chylomicrons- biggest- main component = triglycerides = least dense
- Very low density lipoproteins (VLDL)- Main component = triglycerides, slightly more dense than above
- Low density lipoproteins (LDL)- “bad cholesterol’ - lots of cholesterol- tries to deposit around the body
- Intermediate density lipoprotein (IDL)- Main component = cholesterol
- High density lipoproteins (HDL)- “Good cholesterol”- mainly protein = most dense, takes cholesterol out of tissue and back to the liver
What is known as good cholesterol?
High density lipoproteins (HDL)
What is known as bad cholesterol?
Low density lipoproteins (LDL)
Describe the exogenous and endogenous cholesterol pathways (like exam q)
EXOGENOUS
- Lipids (cholesterol and triglycerides) from the diet are absorbed in the GI tract- ileum (intestine) and are assembled into chylomicrons
- The chylomicrons can then travel in the bloodstream to peripheral tissues e.g. adipose tissues
- In these peripheral tissues, chyomicrons release their fats and TG is hydrolysed by lipoprotein lipase to glycerol and free fatty acids. These are taken up into the tissue to provide energy
- After, they have unloaded their fats, chylomicrons are smaller and are known as chylomicron remnants- they are empty HDL.
- Chylomicron remnants containing cholesteryl esters then travel to the liver and the apoE segment binds to a remnant receptor (LDL receptors). They are then endocytosed and releases any cholesterol and free fatty acids into liver.
- Cholesterol is then stored in the liver and oxidised to bile acids or enters the endogenous pathway
ENDOGENOUS
- Cholesterol arriving from the diet (15%) (as in pathway above) or liver (85%) and newly synthesised triglycerides are re-packaged as VLDLs. Inbetween meals, they enter the bloodstream and travel to peripheral tissues e.g. muscle and adipose tissue
- Triglycerides are hydrolysed in tissues by lipoprotein lipase to monoglycerides (glycerol) and free fatty acids (fatty acids are taken up into the cell)
- After unloading, VLDL becomes much smaller but retain cholesteryl esters = now known as IDLs
- These bind to LDL receptors- cells recognise apoprotein AP0B100 and are taken up into hepatocytes. They are then broken down by hepatic lipase into LDLs
- LDLs have relatively high cholesterol content and minimal TG and fatty acid content. Some cholesterol is deposited in tissues as these circulate for membranes/steroid hormones/etc
- Leftover cholesterol, is returned to the plasma and then liver for tissues = reverse cholesterol transport via LDL receptors.
- cholesterol can also be esterified with long chain fatty acids in HDL to VLDL or LDL by cholesteryl ester transferase
Reverse cholesterol transport:
- If there is too much cholesterol in peripheral tissues, the ABCA1 receptor is activated (on peripheral tissue)
- Pre-beta HDl (protein-rich, disc shaped particle that is empty of cholesterol) then interacts with this receptor and collects the cholesterol to be returned to the liver. Causes HDL shape to change.
- This prevents over-deposition of cholesterol leading to atherosclerosis.
- Lecithin cholesterol acetyltransferase (LCAT) enzyme esterifies cholesterol to esters and are then transferred by CTEP enzyme back to the liver so cholesterol can be excreted.
What is the LDL receptor pathway?
This pathway is important for lipid and cholesterol uptake into the liver
- All nucleated cells have LDL receptors - but there is an increased expression on hepatocytes
- LDL binds to these receptors= receptor-mediated endocytosis
-LDL is taken up into a coated vesicle - These vesicles have a decrease in pH levels (7–>5) = LDL lipoprotein dissociates from the LDL receptor
- The vesicle pinches apart into 2 smaller vesicles- 1 contains the receptor and 1 contains the LDL lipoprotein
- The vesicle containing the lipoprotein fuses with a lysosome- enzymes lead to release of cholesterol into cytosol= used for its function in membranes, steroids hormones, bile acids
- The vesicle containing the receptor are recycled back onto the cell surface- vesicle fuses with cell membrane = exocytosis of receptor to be used again
LOOK AT DIAGRAM IN ORANGE BOOK
Discuss the process of reverse cholesterol transport
- Excess cholesterol from cells is taken back to the liver for excretion
- We make HDL in the liver and small intestine= pre-beta HDL (not yet mature) (is disc shaped and free from cholesterol)
- It then takes up cholesterol from tissues. This causes its shape to change
- LCAT (lecithin cholesterol acyltransferase) enzymes esterifies cholesterol to cholesterol esters = HDL molecules become spherical
- Cholesterol Estes are transferred by CTEP (cholesterol ester transferase protein) enzyme
- picks up triglycerides
- HDL back to liver so cholesterol can be excreted = is recycles back to pre-beta HDL to be reused
What are lipid levels like in dyslipidaemia?
High total cholesterol, LDL and triglycerides
Low HDL
What are the recommended lipid levels?
<5mmol/L Total cholesterol
<3mmol/L LDL
What is the treatment aim when reducing lipid levels?
Aim for a greater than 40% decrease in non-HDL cholesterol
What is the difference between primary and secondary dyslipidaemia?
Primary = 60%
- Is a combination of diet and genetics
Diet:
High saturated fat
Inactive
Overweight
Smoker
Large waist circumference
Genetics:
There are 5 inherited conditions
Secondary (40%)
- Has an underlying cause
- Disease e.g. diabetes, liver disease, hypothyroidism, renal failure
or drug e.g. thiazide-like diuretics, loop, b-blockers, Ciclosporin
What are the inherited conditions that cause dyslipidaemia?
FAMILY HYPERCHOLESTERAEMIA:
- Inherited high cholesterol levels from birth
- Caused by a mutation in LDL receptors, Apob or PCSK9
- Cholesterol can increase above 20mmol/L
FAMILIAL COMBINED HYPERLIPIDAEMIA:
- inherited
- high cholesterol and triglyceride levels- raised by 20-30 years old
- increased in VLDL
TYPE 3 HYPERLIPIDAEMIA:
High cholesterol and triglyceride
caused by mutations in Ap0E
POLYGENIC HYPERCHOLESTRAEMIA:
- More than 1 gene is changed
>12 genes have been linked to high cholesterol
PRIMARY HYPERTRIGLYCERIDAEMIAL
- Lipoprotein lipase deficienct- can’t hydrolyse triglycerides to glycerol and fatty acids
LYPOSOMAL ACID LIPASE DEFICIENCY
What are the signs of hyperlipidaemia?
- Corneal arcus- lipid deposits forming a white ring around the iris
- Tendon xanthomas- cholesterol deposited into the skin causes raised bumps around joints/tendons
- Patches around they eyes- yellow deposits of cholesterol
What are the non-pharmacological treatments for high cholesterol/dyslipidaemia?
- Dietary modifications:
Decreased sat and trans fat
Increase mono or polyunsaturated fats
Oily fish twice a week
Plant sterols and stanols- decrease cholesterol absorption from gut e.g. benacol
High fibre - Weight loss- BMI <25
- Smoking cessation
- Physical activity- 30 mins 5 x a week
- Decrease alcohol intake
