Post absorption processing of lipids

Question 1

what are some roles of fats

Answer 1

energy store
incorporation into the cell membrane (phospholipids and cholesterol)
precursors for prostaglandins, leukotrienes and thromboxane

Question 2

what are the 4 uses of cholesterol

Answer 2

bile salts
membranes
vit D
steroid hormones

Question 3

name 5 steroid hormones

Answer 3

androgens (testosterone) 
oestrogens
progesterones 
mineralocorticoids (aldosterone) 
glucocorticoids (cortisol)

Question 4

what are the real names of w-3 and w-6

Answer 4

linoleic acid (6)
DHA/EPA (3)

Question 5

what is the role of w-3 and w-6

Answer 5

fatty acids are precursors for both inflammatory and anti-inflammatory molecules

Question 6

describe the pathway of turning linoleic acid (w-6) into arachidonic acid

Answer 6

linoleic acid
y-linoleic acid (GLA)
dihomo-y-linoleic acid (DGLA)
arachidonic acid

Question 7

what can DGLA turn into

Answer 7

1-series
prostaglandins
thromboxanes

Question 8

what can AA turn into and what affects does aspirin have

Answer 8

aspirin increases turning AA into lipoxins
aspirin decreases 2-series prostaglandins and thromboxane
can also turn into 4-series leukotrienes

Question 9

what can DHA/EPA (w3) turn into and what affect does aspirin have on it

Answer 9

3-series protoglandins and thromboxanes
aspirin increases turning into protectins and resolvins
5-series leukotrienes

Question 10

what are chylomicrons and how do they enter the subclavian vein

Answer 10

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

Question 11

do chylomicrons pass from GI tract to liver

Answer 11

no

Question 12

what are the two ways in which fatty acts arrive at peripheral tissue

Answer 12

in chylomicrons or VLDL

from adipose tissue

Question 13

what releases fatty acids from chylomicrons and VLDLs in peripheral tissue

Answer 13

lipoprotein lipase

Question 14

how do fatty acids get to adipose tissue

Answer 14

triaglycerols broken down by hormone sensitive lipase
fatty acids released into blood
transported to tissues bound to albumin

Question 15

does he brain receive fatty acids

Answer 15

no as fatty acids can’t cross the blood brain barrier

Question 16

describe the process of oxidation of fatty acids

Answer 16

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

Question 17

what is the specific role of carnitine

Answer 17

transports fatty acids across the inner mitochondrial membrane

Question 18

describe the process of B oxidation of fatty acids

Answer 18

spiral process

each turn releases 1 acetyl CoA producing NADH and FADH2

Question 19

what happens to the products of the B oxidation of fatty acid

Answer 19

NADh and FADH2 are oxidised in the electron transport chain

acetyl CoA enters the krebs cycle producing more NADH

Question 20

what is the overall product of the B oxidation of fatty acids and what type of process is this

Answer 20

108 ATP from each molecule of palmitoyl CoA

completely aerobic

Question 21

what produces more ATP oxidation of glucose or b oxidation of palmitoyl CoA

Answer 21

36 from oxidation of glucose but 108 from the other but this is totally dependant on oxygen

Question 22

how is b oxidation controlled

Answer 22

regulated by amount of fatty acids present in the mitochondria which is controlled by the concentration of malonyl CoA
ie regulation of substrate availability

Question 23

how is malonyl CoA produced

Answer 23

formed y acetyl CoA carboxylase in first step of fatty acid synthesis

Question 24

what inhibits carnitine acyl-transferase-1

Answer 24

high concentrations of malonyl CoA

Question 25

what are ketone bodies formed from and where does this process occur

Answer 25

excess acetyl CoA mitochondria of liver cells under fasting or uncontrolled diabetes

Question 26

what are ketone bodies used for

Answer 26

released into the blood and are oxidised to produce energy in peripheral tissues including the brain tissue

Question 27

what do high levels of ketones cause and give examples

Answer 27

high levels of ketone bodies acetoacetate & beta hydroxybutyrate in blood affect pH, create ketoacidosis – this can be fatal – leads to coma and death

Question 28

why is cholesterol good and bad

Answer 28

needed as vital part of cell membrane precursor to many molecules high levels implicated in CVD and AD

Question 29

what are the two sources of cholesterol and give examples

Answer 29

from diet such as egg(yolk) liver, meat | synthesis in mainly liver and intestine

Question 30

what effect does plant sterols have on cholesterol uptake

Answer 30

inhibits uptake in the gut which helps lower plasma cholesterol

Question 31

describe cholesterol uptake from LDL via receptor mediated endocytosis

Answer 31

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

Question 32

what are the 4 steps of cholesterol biosynthesis

Answer 32

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

Question 33

where does biosynthesis of cholesterol occur in the body

Answer 33

in cytosol and smooth endoplasmic reticulum

Question 34

how is synthesis of cholesterol controlled

Answer 34

by adjusting the activity or amount of HMG CoA reductase high levels of cholesterol inhibit synthesis insulin increases synthesis whereas glucagon inhibits

Question 35

how can you affect the enzyme of HMG CoA reductase to affect levels of cholesterol

Answer 35

``` controlled of transcription of the enzyme (mRNA synthesis) - inhibited by high cholesterol - stimulated by insulin rate of degradation of enzyme -increased by high cholesterol ```

Question 36

what is SREBP and what does it do

Answer 36

– 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

Question 37

how do humans get rid of cholesterol

Answer 37

cannot be broken down and only can be excreted in faeces via bile salts

Question 38

excess lipids are commonly associated with what diseases

Answer 38

coronary heart disease strokes alzheimers steatohepatitis which leads to cirrhosis and hepatic carcinoma

Question 39

what is the uk target for cholesterol levels

Answer 39

5mM for healthy or less | 4mM or less for those at risk

Question 40

what are the good vs the bad fats

Answer 40

mono/polyunsaturated fats are good | bad are saturated fats, trans fats and cholesterol

Question 41

what is the disease difference in high levels of HDL vs LDL

Answer 41

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

Question 42

what is tangier disease

Answer 42

lack of HDL which increases risk of coronary disease

Question 43

what is atherosclerosis and how does it form

Answer 43

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

Question 44

describe the link between cholesterol levels and alzheimer's

Answer 44

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

Question 45

what does accumulation of fats in the liver lead to

Answer 45

inflammation and fibrosis which leads to hepatitis

Question 46

what is the difference between alcoholic and non-alcoholic steatohepatitits

Answer 46

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