Exam 3 Lipid Metabolism I part a

Question 1

what is the major source of carbon for FA synthesis?

Answer 1

dietary carbohydrates (carbs we eat is converted into FAs)

Question 2

FA synthesis occurs primarily in _ but also _

Answer 2

primarily in liver but also in adipose tissue

Question 3

FA synthesis requires coordination between _ and _ reactions

Answer 3

cytosolic and mitochondrial reactions

Question 4

what is the precursor of FA synthesis?

Answer 4

Acetyl CoA (2 carbon molecule)

Question 5

what is phase I in FA synthesis

Answer 5

cytosolic entry of Acetyl CoA (made in the mito matrix but needed in cytoplasm)

Question 6

what is phase II in FA synthesis

Answer 6

generation of malonyl CoA (a 3 carbon molecule, from 2 carbon acetyl CoA, that is a substrate catalyzed by FA synthase)

Question 7

what is phase III in FA synthesis

Answer 7

FA chain formation (7 reactions catalyzed by FA synthase)

Question 8

how do we get acetyl coA into the cytosol?

Answer 8

1. citrate synthase catalyzes acetyl coA with OAA into citrate (in mito matrix) and citrate is trasported out

Question 9

what happens when citrate is trasported to the cytosol?

Answer 9

citrate lyase converts citrate back into acetyl coA and OAA.

Question 10

what happens to the products of citrate lyase?

Answer 10

acetyl coA is used for FA synthesis and OAA is reduced to malate by malate dehydrogenase

Question 11

how do we regenerate OAA?

Answer 11

1. cytosolic malate is converted into pyruvate which is transported into the mito
2. malate transported to mito and oxidized into OAA by malate dehydrogenase

Question 12

what is the RLS of FA synthesis

Answer 12

acetyl coA (2-C) converted into malonyl coA (3-C)

Question 13

what is the rate limiting enzyme of FA synthesis

Answer 13

acetyl coA carboxylase (ACC)

Question 14

where do we get the 3rd carbon from to make malonyl coA?

Answer 14

CO2

Question 15

ACC uses ATP and _ as cofactor

Answer 15

biotin

Question 16

malonyl coA is a substrate for FA Synthase (FAS) and acts like its regulator how?

Answer 16

inhibits carnitine acyltransferase (RLS in FA degradation)

we want to go foward with malonyl coA so inhibits degradation of FA since we want synthesis

Question 17

how do we accomplish phase III, FA chain formation?

Answer 17

2-C units from malonyl coA are sequentially added to growing fatty acyl chain in 7 rxns to form palmitate (16:0)

Question 18

FAS complex is present where?

Answer 18

in cytoplassm

Question 19

FAS is a large _ complex

Answer 19

multi-enzyme

Question 20

FAS is composed of _ arranged in _ to _ conformation

Answer 20

2 identical dimers arranged in head to tail conformation

Question 21

Each monomer, of the dimer of FAS, has _ enzyme activities and an _ protein

Answer 21

7 enzymatic activities and an acyl carrier protein (ACP)

Question 22

what is the purpose of ACP having a flexible arm?

Answer 22

Function is to pick a substrate and take it to one of the 7 enzymes and then takes product (substrate) forfmed to the next enzyme in chain

Question 23

Stoichiometry:

1 acetyl coA + 7 malonyle coA + 14 NADPH + 14 H+ =

Answer 23

palmitate + 14 NADP+ + 8 CoA + 6 H2O

Question 24

why does FA synthesis use NADPH?

Answer 24

accessory component that helps in reduction

Question 25

what are the sources of NADPH?

Answer 25

malic enzyme yields 1 molecule of NADPH and PPP yields 2-12 molecules of NADPH

Question 26

what is the cycle of FAS?

Answer 26

condensation, reduction, dehydration, reduction (repeated 6x more)

Question 27

what are the 3 enzymes of FA synthesis regulation?

Answer 27

1. ATP citrate lyase (phase I)
2. acetyl coA carboxylase (phase II and RLS)
3. FA synthase (phase III)

Question 28

how is ATP citrate lyase stimulated/induced?

Answer 28

1. stimulated by phosphorylation

2. gene expression induced by glucose/insulin (high glucose/high insulin want to convert into storage FA form)

Question 29

how is ATP citrate lyase counteracted/negated?

Answer 29

1. induction of gene expression counteracted by polyunsaturated FAs (PUFAs)
2. induction of gene expression counteracted by leptin (H that senses fat content in body)

Question 30

ACC is inactive _, active _

Answer 30

inactive dimer, active polymer

Question 31

ACC allosteric reguolation?

Answer 31

1. citrate activates

2. long chain FAs (palmitate) inactivate

Question 32

ACC phosphorylation?

Answer 32

phosphorylation = inactivated

1. epinephrine activates PKA
2. glucagon activates PKA
3. AMP activates AMP kinase (energy sensor)

Question 33

ACC dephosphorylation?

Answer 33

dephosphorylation = activation

1. insulin activates protein phosphatase

Question 34

ACC induction?

Answer 34

gene expression up-regulated by high carb/low fat diet

Question 35

what increases allosteric effect activity in regulation of FAS?

Answer 35

presence of phosphorylated sugars ie G6P/G1P

Question 36

what induces gene levels in regulation of FAS?

Answer 36

1. insulin and glucocorticoid hormones INCREASES synthesis

2. high carb/low fat diet INCREASES synthesis

Question 37

what represses gene levels in regulation of FAS?

Answer 37

1. high fat diet and STARVATION lowers synthesis

2. high PUFA suppresses synthesis