Lipids Flashcards
Functions of lipids
Phospholipids & cholesterol - cell membranes
TG = key energy store
Steroids and fatty acids play regulatory roles as hormones, vitamins and bile acids
Cellular energy - short-term storage
ATP (and other phosphate bonds) Redox agents (NADH, FADH2) Ionic transmembrane gradients H+ across mito memb, Na+ across Plasma Membrane All of the above are labile
Limit on ATP stored
Some energy is stored intracell as creatine phosphate
Carbohydrate as energy
Sugars are absorbed from gut into blood stream
Sugars absorbed by liver and stored as glycogen
Via hepatic portal vein
Also sugars stored throughout body as glycogen:
Glucose spike leads to insulin
Glycogen is broken down into glucose when more is needed
No glycogen in brain: it needs glucose or ketone bodies from plasma constantly
Citric acid cycle
A-CoA + Oxalo-acetic acid -> Citric acid (6C)
Citric acid + O2 -> Oxalo-acetic acid + CO2 + ATP
Fatty Acid Synthesis
Acetyl-CoA + ATP + e- (ATP) -> fatty acid + CO2 + CoA
Fatty Acids
Simple straight C chain + COOH 16-20Cs
50% have double bonds
Cholesterol
Essential component of cell membranes
precursor of bile acids, steroid hormones and vitamin D
Sources: from diet OR made in liver
A major emphasis on recycling
Bile salts
Endogenous pathway
Cholesterol esters
75% of plasma cholesterol is esterified
Broken down by lipase to free cholesterol & FA
Acetyl-Coenzyme A
Main energy production precursor
Cannot be transported in plasma
Ketone
“Ketone bodies” are 3 soluble chemicals
Made from acetyl-CoA during fasting
By liver
Last for only 5 hours
During fasting, major energy source
Acetoacetic acid & beta-hydroxybutyric acid
Acetone is a waste product
Made spontaneously by decarboxylation
eliminated by kidney
Kink(veg)
Lowers melting temperature
Fats
Saturated fats are bad
- Increase LDL
Trans unsaturated fats are bad
Cis unsaturated fats are either Monounsaturated Polyunsaturated Health information on these changes but they are probably good for you Lower melting temperature b/c of kink
Exogenous Pathway
From gut to liver (and to periphery)
Diet and packaged into chylomicrons in small intestine
Endogenous Pathway
From liver to periphery
Peripheral lipids stored in adipose & muscle
Endogenous = made by the body
Lipid from liver packaged into VLDL
Reverse Cholesterol Transport
From periphery to liver
Occurs when lipid supplies in liver are being exhausted
HDL in blood indicates reverse path activity
Bile production
From liver into gut (and gall bladder)
- Bile released into cystic duct
Cholesterol converted into bile acids
- Bile is necessary to digest fats in diet
- Emulsifies fats
Most bile acids are reabsorbed by gut
- Returned to the liver and recycled
Lipoprotein lipase
Metabolises TG -> fatty acids + glycerol
Because TG cannot go through cell membrane
Cell surface-linked enzyme in capillary walls
In order to remove triglycerides from VLDL and to move the TG across the capillary membrane, TG must first be metabolised via lipoprotein lipase
Lipoprotein particles
In plasma
Soluble and carry lipids
Apolipoproteins
Proteins in LP particles that can hold lipids
Lipid identified by density
Lipid is much less dense than protein
TG are very low density
Cholesterol is midway between TG and protein
LDL
LDL contents get incorporated into atheromas
LDL in blood may be “storage” for cholesterol that “cannot be stored elsewhere”
Excess LDL accumulates in atheromas
Left over LDL absorbs endogenous TG from VLDL from liver
HDL
Increased HDL -> lower CV risk
lipid transport from fat cells to liver
VLDL
Signifies risk of atheroma
Used to transport endogenous cholesterol and TG from Liver to adipose and muscle
After TG is removed by periphery from VLDL, leaves over IDL
IDL
Results from VLDL losing TG to periphery
IDL will become LDL
Chylomicrons
Not usually associated with CV risk
Normally high after fat-containing meals
Carries lipids from gut to periphery
For exogenous lipids
Hypercholesterolaemia
High fasting levels of plasma cholesterol
Increased risk of arteriosclerosis
HDL reduces risks
Due to a combination of environmental and genetic factors
Statins
Drugs used to treat hypercholesterolaemia
Block endogenous cholesterol synthesis
By Blocking HMG-CoA Reductase
The entry step into cholesterol synthesis
Metabolic syndrome
Group of risk factors that occur together, leading to increased risk for CAD, stroke, and type 2 diabetes
Main causes
Insulin resistance
Central obesity
Waist circumference
Endothelial injury due to
raised LDL
‘toxins’ eg cigarette smoke
hypertension
haemodynamic stress
Endothelial injury causes
platelet adhesion, PDGF release, VSMC proliferation and migration
insudation of lipid, LDL oxidation, uptake of lipid by VSMC and macrophages
migration of monocytes into intima
Stimulated VSMC produce matrix material
Foam cells secrete cytokines causing
further VSMC stimulation
recruitment of other inflammatory cells
