Fatty Acid Synthesis

Question 1

fatty acid synthesis definition

Answer 1

the formation of fatty acids from acetyl CoA and NADPH, catalysed by fatty acid synthases

Question 2

benefits of fatty acid synthesis

Answer 2

able humans to store excess carbohydrate and protein energy, preventing energy wastage

Question 3

differences in chemistry and mechanics of fatty acid synthesis and oxidation

Answer 3

chemically they are the reverse

mechanistically the processes are different

Question 4

where are fatty acids synthesised?

Answer 4

cytosol of the liver

Question 5

where are they stored + as what?

Answer 5

TAGs in adipose tissue

Question 6

stages of fatty acid synthesis

Answer 6

1. acetyl-CoA and a bicarbonate ion, and ATP to form malonyl CoA and ADP + Pi- catalysed by acetyl- CoA carboxylase
2. intermediates linked to ACP, acyl carrier protein- acetyl-CoA to acetyl-ACP and malonyl-CoA to malonyl ACP catalysed by acetyl transacylase and malonyl transacylase respectively
3. acetyl-ACP and malonyl-ACP condensed form acetoacetyl-ACP and carbon dioxide and ACP, catalysed by B-ketoacyl-ACP synthase
4. acetoacetyl-ACP + NADPH reduced to form D-B-hydroxybutyryl-ACP catalysed by B-ketoacyl-ACP reductase
5. D-B-hydroxybutyryl-ACP dehydrated to A,B-trans-butenoyl-ACP with release of water, catalysed by B-hydroxyacyl-ACP dehydratase
6. a,B-transbutenoyl-ACP reduced to butyryl-ACP using NADPH and catalysed by enoyl-ACP reductase

Question 7

what happens next?

Answer 7

after the first pass through the cycle, the subsequent passes add more malonyl-ACP molecules, elongating the fatty acid chain by 2 each time

Question 8

last stage of palmitate synthesis

Answer 8

after the 7th reduction cycle, palmitoyl-ACP is converted to palmitate using H2O and is catalysed by palmitoyl-thioesterase

Question 9

energy cost of one molecule of palmitate

Answer 9

8 acetyl-CoA, 7ATP, 14 NADPH, 6H+

Question 10

produced

Answer 10

palmitate, 8 CoA, 6 H2O, 14 NADP, 7 ADP, 7Pi

Question 11

How is fatty acid synthesis different to oxidation?

Answer 11

1. elongation by a 3 carbon unit malonyl CoA, whereas oxidation is degradation into 2 carbon units acetyl- CoA
2. intermediates linked to ACP, not CoA
3. reductant NADPH as opposed to oxidants NAD+ and FADH
4. enzymes joined in a single polypeptide chain FAS, not separate
5. takes place in the cytosol, not the mitochondria

Question 12

What is FAS?

Answer 12

fatty acid synthase, multifunctional dimeric enzyme, where each monomer is a multi-catalytic peptide

7 different enzymatic activities with a phosphopantetheine binding domain

Question 13

Where is acetyl-CoA normally found and why is this a problem?

Answer 13

within the mitochondria

it cannot pass through the highly impermeable inner membrane

Question 14

Explain how this is overcome

Answer 14

1. instead citrate is exported from the mitochondria via the tricarboxylate transporter into the cytosol
2. ATP-citrate lyase then catalyses the addition of CoA-SH along with ATP to form OAA and acetyl-CoA

Question 15

3 ways fatty acid synthesis is regulated

Answer 15

allosteric

covalent- hormonal

covalent- intracellular

all at acetyl-CoA carboxylase

Question 16

explain allosteric regulation

Answer 16

acetyl-CoA carboxylase is activated by citrate

inactivated by long chain fatty acyl-CoA

Question 17

explain covalent hormonal regulation

Answer 17

too much glucose, insulin is secreted which activates protein phosphatase 2A, which dephosphorylates acetyl-CoA carboxylase to activate it

glucagon and adrenaline stimulate PKA, which phosphorylates the active enzyme to inactivate it- more lipids used for energy as less needed for storage

Question 18

explain covalent intracellular regulation

Answer 18

AMP forms AMPK which phosphorylates the enzyme

Question 19

what form are fatty acids stored in?

Answer 19

triacylglycerols

Question 20

stages of fatty acid esterification

Answer 20

1. fatty acyl-CoA and glycerol-3-phosphate form lysophophatidic acid, catalysed by glycerol-3-phosphate acyltransferase
2. lysophosphatidic acid + fatty acyl-CoA forms phosphatidic acid, catalysed by acylglycerol-3-phsophate acyltransferase
3. phosphatidic acid, loss of Pi by phosphatidic acid phosphatase forms diacylglycerol
4. fatty acyl-CoA + diacylglycerol forms triacylglycerol, catalysed by diacylglycerol acyltransferase