Lecture 6 Flashcards
Which parts of the lipid are hydrophillic and hydrophobic?
Head of the lipid - Polar and so hydrophillic
Tail of the lipid - non polar and so hydrophobic
What is meant by an unsaturated and a saturated fat?
Saturated - no double bonds (stearic acid)
Unsaturated - Has double bond(s) (linoleic acid) has a cis double bond (if trans bond turns into a trans fat)
How are triglycerides formed?
Through dehydration synthesis, from fatty acids and glycerol
Why are phospholipids important?
They are integral to the cell membrane and lipoproteins
What can cholesterol be metabolised to?
- Steroid hormones
- Bile acids
- Vitamin D
How are cholesterol esters formed and where are they stored?
- Formed when there is an excess of cholesterol through an enzymatic reaction of cholesterols polar head turning it from a hydroxyl group to an ester group
- Stored as cytosolic lipid droplets
What is the reaction needed to change cholesterol esters back to cholesterol?
Cholesteryl ester —-> cholesterol
- using cholesterol esterase and water
- as well as cholesterol it produces fatty acids
What are the main sources of cholesterol?
- food such as eggs, meat and cheese
- the liver
How are lipids that are insoluble in an aqueous environment transported through the human body?
- Through the macromolecular complex called a lipoprotein
- They have an inner hydrophobic core made up of esterified cholesterol and triglyclerides
- They have an outer hydrophillic core that consists of unesterified cholesterol (because of its OH group), phospholipids and apolipoprotein
What are the types of different lipoproteins?
- Chylomicrons
- Very low density lipoproteins (VLDL)
- Low density lipoproteins (LDL)
- High density lipoproteins (HDL)
What are the key facts about chylomicrons?
- They are the largest type of lipoprotein
- They form in the intestine from dietary lipids, they then enter the bloodstream
- Their outer core consists of phospholipids, cholesterol and apolipoproteins
- Their inner core consists of triacylglycerols and cholesteryl esters
What are the key facts about low density lipoproteins (LDL)?
- Consists mainly of cholesterol, which it delivers to peripheral tissues
- LDL receptors on the peripheral cells/ tissues bind to the LDL via apoprotein B100 (ApoB100)
- The LDL is internalised and the cholesterol is released into the cell
- This is the BAD cholesterol
What are the key facts about High density lipoprotein (HDL)?
- HDL is the smallest lipoprotein
- It mainly consists of apoproteins
- HDL collects excess cholesterol from peripheral tissue and returns it to the liver
- HDL is also produced by the liver
- This is the GOOD cholesterol
What are the highest percentage composition components of each of the lipoproteins?
- Chylomicron - triglycerides (98%)
- LDL - cholesterol (60%)
- HDL - Protein (50%)
What are the lipid metabolic pathways?
The exogenous pathway and the endogenous lipid metabolism
What happens during the exogenous metabolism?
- liver produces bile acids and cholesterol and they are combined with the dietary lipids that then all transported to the small intestine
- form the small intestine the chylomicrons are produced
- the chylomicrons are then transported in the blood through the capillaries transporting different products to muscle and adipose cells
- a chylomicron remnant emerges from the capillaries and binds back with the liver where it is metabolised
What happens during endogenous lipid metabolism?
- liver produced VLDL which travels through the capillaries and after supplying tissue with products emerges as IDL
- IDL can bind specifically to the liver to be metabolised or it can be made into LDL
- the LDL can then travel and bind to specific receptors on peripheral tissues or it can bind to the liver to be metabolised
What are the functions of all the lipoproteins?
Chylomicrons - Transport dietary lipids to the liver and other tissues
VLDL - Gets produced by the liver and as they circulate in the tissues they give up their triacylegylcerol and become LDLs which are taken up by tissues
HDL - Transport cholesterol from the tissues back to the liver
What is the LDL metabolism?
- When the LDL docks with an LDL receptor it makes the lipoprotein-receptor complex which then undergoes endocytosis
- Once inside the cell the LDL gets degraded and cholesterol enters the cytoplasm
- Excessive accumulation of this cholesterol can lead to atherosclerosis
What is the HDL metabolism?
- Essential for removing excess cholesterol from cells
- Transporter moves cholesterol from the cytosolic leaflet to the extracellular leaflet where it can diffuse into the HDL
- Defects in the genes of the transporter causes tangier disease characterised by accumulations of cholesterol in tissues and a high risk of heart attack
How are triglycerides digested?
- They are first emulsified [The breaking down of large fat globules to small ones]
- They then undergo enzymatic hydrolysis via lipase enzymes
What happens during emulsification?
- The fat droplet gets a ‘soapy layer’ that consists of bile salts and phosphatidyl choline (lecithin) and a pancreatic lipase starts to digest the fat droplet
- The digestion of the fat droplet causes micelle formation (lots of smaller fat droplets)
What are the different lipases that are involved in the enzymatic hydrolysis of lipids in the human body?
- Lingual lipase
- Gastric lipase
- Pancreatic lipase
- Intestinal lipase
What is the major site of lipid digestion?
The small intestine
Which lipase is the most active in the lipid metabolism?
Pancreatic lipase
What does pancreatic lipase actually do?
It hydrolysed the fatty acids in positions 1 and 3 of the triacylglyerol producing a monoglyceride and free fatty acids
Why are fatty acids so important to us as humans?
- They can go on to produce membrane lipids that are a key part of the phospholipid bilayer of a cells membrane
- They can also undergo Beta oxidation with the production of FADH2 and NADH to make Acetyl CoA which can then enter into the citric acid cycle, eventually producing ATP
Where are drugs mostly metabolised?
In the liver
What often happens during the drug metabolism?
- Metabolism often increases the drugs polarity which facilitates its excretion via the kidneys
- The toxicity of the drug reduces (not always though)
Where do all of the reactions that make up the drug metabolism happen?
They occur in the Hepatic Microsomal Enzyme System (MES)
What are the 2 routes a drug can take when getting metabolised by the liver?
It can be broken down into reactive metabolites (these can lead to the covalent modification of cellular macromolecules leading to toxicity)or stable metabolites (these just get excreted)
What is a cytochrome P450?
The Cytochrome P450s are a family of enzymes containing heme as a cofactor that function as monooxgenases
What is the role of cytochrome P450?
- Helps during the synthesis of steroid hormones, cholesterol and vitamin D
- Drug metabolism
- Electron transport chain
What happens if the Cytochrome P450 enzymes become inhibited?
There will be too much of the drug accumulating in the body that could become lethal, the drug will find it very hard to be metabolised and excreted
