metabolic pathways and ATP production

Question 1

synthesis of 3-isopentenyl pyrophosphate in the cytoplasm from acetyl CoA (5 steps)

Answer 1

2 acetyl CoA → acetoacetyl CoA (via B-ketothiolase, producing CoA); acetoacetyl CoA + acetyl CoA → HMG-CoA (via HMG-CoA synthase, requiring water and producing CoA); HMG-CoA → mevalonate (via HMG-CoA reductase, using 2 NADPH molecules and 2H+, and producing 2 NADP+ and CoA); sequential phosphorylation at 3’ and 5’ OH (3 ATP by kinases); decarboxylation (requiring CO2 and Pi) to form 3-isopentenyl pyrophosphate

Question 2

what is the significance of mevalonate in cholesterol synthesis

Answer 2

control point - regulated by negative feedback to lower cholesterol

Question 3

what does mevalonate regulate and how

Answer 3

regulates HMG-CoA reductase via end-product inhibition

Question 4

besides cholesterol, what also regulates mevalonate

Answer 4

bile

Question 5

synthesis of squalene in the cytoplasm from 3-isopentenyl pyrophosphate (5 steps)

Answer 5

3-isopentenyl pyrophosphate → 6-isopentenyl pyrophosphate (via isomerase); → dimethylallyl pyrophosphate (via isomerase); dimethylallyl pyrophosphate + isopentenyl pyrophosphate → geranyl pyrophosphate (via geranyl transferase, producing PPi); geranyl pyrophosphate + isopentenyl pyrophosphate → farnesyl pyrophosphate (15C; via geranyl transferase, producing PPi); 2x farnesyl pyrophosphate + NADPH → squalene (30C; via squalene synthetase, producing 2PPi, NADP+ and H+)

Question 6

as squalene is 30C, how many isopentenyl pyrophosphate molecules are required to synthesise 1 molecule

Answer 6

6

Question 7

synthesis of cholesterol in the ER from squalene

Answer 7

cyclicisation and demethylation to lanosterol (multiple intermediates, via squalene monoygenase then by squalene epoxide lanosterol-cyclase); 19 stages (reduction and 3 demethylations) to form cholesterol

Question 8

what is significant about lanosterol

Answer 8

4C ring structure

Question 9

what happens when cholesterol is stored

Answer 9

acylated at C3

Question 10

in the synthesis of bile salts or steroid hormones, what is cholesterol converted to, and by what

Answer 10

precursor pregnenolone by desmolase

Question 11

what are the 5 classes of steroid hormone

Answer 11

progestogens, glucocorticoids, mineralcorticoids, androgens, oestrogens

Question 12

what is the form of bile salts

Answer 12

micelles (hydrophilic face away from triacylglycerols and hydrophobic face them)

Question 13

give two examples of bile salts

Answer 13

glycocholate, taurocholate

Question 14

how is cholesterol converted into vitamin D3

Answer 14

7-dehydrocholesterol converted to vitamin D3 via UV and hydroxylation

Question 15

what is calcitriol involved in

Answer 15

Ca2+ metabolism

Question 16

what does vitamin D3 deficiency cause

Answer 16

rickets

Question 17

what transports cholesterol when aqueous

Answer 17

lipoproteins

Question 18

3 components of lipoproteins

Answer 18

phospholipid monolayer, cholesterol, apoproteins

Question 19

what is the function of apoproteins

Answer 19

allow particle to be recognised by tissue

Question 20

what is inside a lipoprotein

Answer 20

cholesterol esters, triacylglyerols

Question 21

what are cholesterol esters synthesised from

Answer 21

cholesterol and acyl chain via LCAT catalysed reaction, or from fatty acyl CoA via ACAT catalysed reaction

Question 22

function of hedgehog signalling protein in embryogenesis

Answer 22

limit diffusion within tissue to allow for successful limb formation

Question 23

what are micelles absorbed by

Answer 23

enterocytes in small intestine to be resynthesised

Question 24

5 types of lipoproteins

Answer 24

CM, VLDL, IMDL, LDL, HDL

Question 25

LDL vs HDL

Answer 25

LDL: “bad”, increase % cholesterol esters, prolonged elevation causing atherosclerosis, transport fatty acids as triacylglycerols; HDL: “good”, take cholesterol from tissue and deliver for use or disposal, lowering % cholesterol esters

Question 26

function of chylomicrons (CM)

Answer 26

transport dietary fats in blood and enter via lymphatics

Question 27

what do chylomicrons encounter on capillary endothelial cells

Answer 27

lipoprotein lipase

Question 28

what does lipoprotein lipase do

Answer 28

hydrolyses triacylglycerols to glycerol (to liver for gluconeogenesis) and fatty acids (for B-oxidation)

Question 29

what do sufferers of familial hypercholesterolaemia (FH) lack

Answer 29

functional LDL receptors to mediate endocytosis

Question 30

consequence of FH (dominant)

Answer 30

LDL deposit in arteries leading to occlusion and myocardial infarction (worse if homozygous)

Question 31

5 common mutations in FH

Answer 31

LDLR not synthesised (promoter, frameshift or indel), LDLR not transported, LDLR doesn’t bind to LDL (N-terminus), complex doesn’t cluster in vesicle, LDL not released

Question 32

2 methods of controlling FH

Answer 32

resins in intestine lower LDL and increase HDL, HMG-CoA reductase inhibitors (statins) prevent production of cholesterol