Post absorption processing of lipids Flashcards
what are some roles of fats
energy store
incorporation into the cell membrane (phospholipids and cholesterol)
precursors for prostaglandins, leukotrienes and thromboxane
what are the 4 uses of cholesterol
bile salts
membranes
vit D
steroid hormones
name 5 steroid hormones
androgens (testosterone) oestrogens progesterones mineralocorticoids (aldosterone) glucocorticoids (cortisol)
what are the real names of w-3 and w-6
linoleic acid (6) DHA/EPA (3)
what is the role of w-3 and w-6
fatty acids are precursors for both inflammatory and anti-inflammatory molecules
describe the pathway of turning linoleic acid (w-6) into arachidonic acid
linoleic acid
y-linoleic acid (GLA)
dihomo-y-linoleic acid (DGLA)
arachidonic acid
what can DGLA turn into
1-series
prostaglandins
thromboxanes
what can AA turn into and what affects does aspirin have
aspirin increases turning AA into lipoxins
aspirin decreases 2-series prostaglandins and thromboxane
can also turn into 4-series leukotrienes
what can DHA/EPA (w3) turn into and what affect does aspirin have on it
3-series protoglandins and thromboxanes
aspirin increases turning into protectins and resolvins
5-series leukotrienes
what are chylomicrons and how do they enter the subclavian vein
produced from lipids in diet
formed in intestinal epithelial cells and release into the lymph
enter circulation via thoracic duct and into the subclavian vein
do chylomicrons pass from GI tract to liver
no
what are the two ways in which fatty acts arrive at peripheral tissue
in chylomicrons or VLDL
from adipose tissue
what releases fatty acids from chylomicrons and VLDLs in peripheral tissue
lipoprotein lipase
how do fatty acids get to adipose tissue
triaglycerols broken down by hormone sensitive lipase
fatty acids released into blood
transported to tissues bound to albumin
does he brain receive fatty acids
no as fatty acids can’t cross the blood brain barrier
describe the process of oxidation of fatty acids
activation to fatty acyl CoA in cytosol
First step requires energy – ATP to AMP – priming step (cf glycolysis – phosphorylation)) – attached to CoA
This occurs in cytosol, then FA-CoA needs to be transported into mitochondria
If over 12C use carnitine transport –
3 steps – FA CoA released from CoA, attached to carnitine. Occurs on outer mit memb
Fatty acyl carnitine transferred across inner mit memb by carnitine acylcarnitine translocase – FA-carnitine transported in exchange for free carnitine
FA transferred back to CoA
This transfer is a controlled step – malonyl CoA is early metabolite in FA synthesis pathway – so prevents cycling
what is the specific role of carnitine
transports fatty acids across the inner mitochondrial membrane
describe the process of B oxidation of fatty acids
spiral process
each turn releases 1 acetyl CoA producing NADH and FADH2
what happens to the products of the B oxidation of fatty acid
NADh and FADH2 are oxidised in the electron transport chain
acetyl CoA enters the krebs cycle producing more NADH
what is the overall product of the B oxidation of fatty acids and what type of process is this
108 ATP from each molecule of palmitoyl CoA
completely aerobic
what produces more ATP oxidation of glucose or b oxidation of palmitoyl CoA
36 from oxidation of glucose but 108 from the other but this is totally dependant on oxygen
how is b oxidation controlled
regulated by amount of fatty acids present in the mitochondria which is controlled by the concentration of malonyl CoA
ie regulation of substrate availability
how is malonyl CoA produced
formed y acetyl CoA carboxylase in first step of fatty acid synthesis
what inhibits carnitine acyl-transferase-1
high concentrations of malonyl CoA
what are ketone bodies formed from and where does this process occur
excess acetyl CoA
mitochondria of liver cells under fasting or uncontrolled diabetes
what are ketone bodies used for
released into the blood and are oxidised to produce energy in peripheral tissues including the brain tissue
what do high levels of ketones cause and give examples
high levels of ketone bodies acetoacetate & beta hydroxybutyrate in blood affect pH, create ketoacidosis – this can be fatal – leads to coma and death
why is cholesterol good and bad
needed as vital part of cell membrane
precursor to many molecules
high levels implicated in CVD and AD
what are the two sources of cholesterol and give examples
from diet such as egg(yolk) liver, meat
synthesis in mainly liver and intestine
what effect does plant sterols have on cholesterol uptake
inhibits uptake in the gut which helps lower plasma cholesterol
describe cholesterol uptake from LDL via receptor mediated endocytosis
LDL binds to receptors on cell surface, LDL enters cells via cathrin coated pit and into vesicle then broken down by lysosome into cholesterol which is then repackaged
what are the 4 steps of cholesterol biosynthesis
acetyl CoA to mevalonate (C6)
mevalonate to phosphorylated isoprene units (C5) - activation
polymerise 6 isoprene units to form c30 chain (squalene)
cyclisation to form ring structure (lanosterol) then cholesterol
where does biosynthesis of cholesterol occur in the body
in cytosol and smooth endoplasmic reticulum
how is synthesis of cholesterol controlled
by adjusting the activity or amount of HMG CoA reductase
high levels of cholesterol inhibit synthesis
insulin increases synthesis whereas glucagon inhibits
how can you affect the enzyme of HMG CoA reductase to affect levels of cholesterol
controlled of transcription of the enzyme (mRNA synthesis) - inhibited by high cholesterol - stimulated by insulin rate of degradation of enzyme -increased by high cholesterol
what is SREBP and what does it do
– sterol regulatory binding protein. When cholesterol levels in the ER membrane fall, it sets off a chain of reactions which cause the release of a protein SREBP from the membrance. This protein moves to the nucleus, binds to a sterol resonse elment on the DNA coding for certain genes, including HMG CoA reductase, and the LDL receptor ie stops more production of cholesterol
how do humans get rid of cholesterol
cannot be broken down and only can be excreted in faeces via bile salts
excess lipids are commonly associated with what diseases
coronary heart disease
strokes
alzheimers
steatohepatitis which leads to cirrhosis and hepatic carcinoma
what is the uk target for cholesterol levels
5mM for healthy or less
4mM or less for those at risk
what are the good vs the bad fats
mono/polyunsaturated fats are good
bad are saturated fats, trans fats and cholesterol
what is the disease difference in high levels of HDL vs LDL
high saturated fats and cholesterol in diet causes increased risk of atherosclerosis and CHD
HDL involved in returning cholesterol from peripheral tissues to liver and decrease risk of atherosclerosis
what is tangier disease
lack of HDL which increases risk of coronary disease
what is atherosclerosis and how does it form
inflammatory response
damage to endothelial cells allows LDLs access to subintimal space
LDL become oxidised and are internalised by macrophages - foam cells
accusation of foam cells create bulge in vessel wall ie atherosclerotic plaque
fibrous collagen cap formed
plaque may restrict blood flow and cause angina in coronary vessels
describe the link between cholesterol levels and alzheimer’s
Possession of the APOE4 allele (a form of lipoprotein involved in in cholesterol/lipid transport) increases the risk of developing Alzheimer’s disease
Most studies suggest that increased plasma cholesterol levels correlate with increased risk
High cholesterol diets in animal models cause accumulation of Aβ peptide (the main protein involved in plaques seen in diseased brain)
Some (but not all) studies report a link between statin therapy and decreased incidence of Alzheimer’s disease
what does accumulation of fats in the liver lead to
inflammation and fibrosis which leads to hepatitis
what is the difference between alcoholic and non-alcoholic steatohepatitits
AS - Metabolism of large amounts of alcohol disturbs the balance of fatty acid synthesis and oxidation, inhibiting fatty acid oxidation and activating excess triglyceride synthesis (caused by high NADH levels)
non-AS Insulin resistance leads to increased insulin secretion - this stimulates fatty acid synthesis
