38 Fatty Acid Synthesis

Question 1

what is the storage mechanism for excess glucose?

Answer 1

lipid biosynthesis

Question 2

what structure is the major site for lipid biosynthesis?

Answer 2

the liver to care for its membrane and exported out into the blood to the adipose to be stored and this is done under an insulin signal; remember that fats are oxidized under glucagon and they are formed during insulin

Question 3

where are the FAs synthesized?

Answer 3

in the cytosol

Question 4

what provides the reducing equivalents in FA synthesis?

Answer 4

NADPH

Question 5

what is the starting material for FA synthesis?

Answer 5

acetyl CoA

Question 6

How are the FAs synthesized? meaning through the addition of this incrementally?

Answer 6

by the incremental addition of 2 carbon units from acetyl CoA leading to the predominance of even numbered FA chains

Question 7

since we know that acetyl CoA is the starting material for FA synthesis and that it begins in the cytosol, how can this happen?

Answer 7

Acetyl CoA is formed in the mitochondrial matrix but cannot cross the inner mitochondrial membrane

Acetyl CoA condenses with oxaloacetate (OAA) to form citrate (first reaction of the TCA cycle)

Citrate is transported out of the mitochondrion

Question 8

where is acetyl CoA formed again?

Answer 8

in the mitochondrial matrix but cannot cross the inner mitochondrial membrane

Question 9

what converts pyruvate to acetyl CoA under normal conditions?

Answer 9

pyruvate dehydrogenase

Question 10

what converts pyruvate to OAA under normal conditions?

Answer 10

pyruvate carboxylase and used more frequently when Acetyl CoA is being produced more and citrate is produced and if liver is okay on energy then TCA activity is halted and citrate builds up and so it can leave become cleaved by citrate lyase to produce acetyl CoA

Question 11

what is the number one user for carbs?

Answer 11

the brain

Question 12

in terms of the TCA, is OAA favored or less favored?

Answer 12

less favored because there is a malate OAA that has a positive delta G that favors malate and so less OAA under times when the TCA cycle is not running very fast and this is why pyruvate carboxylase is important

Question 13

what enzyme is necessary for fat/cholesterol synthesis?

Answer 13

citrate lyase

Question 14

what are the two pathways where NADPH is produced?

Answer 14

in the PPP and conversion of malate to pyruvate

Question 15

what is the first enzyme of the PPP?

Answer 15

G-6-P dehydrogenase

Question 16

why is malic enzyme important to note?

Answer 16

Malic enzyme is a key enzyme to have on the “need to know list. If a patient has a problem with NADPH production (Pentose Phosphate pathway), malic enzyme is also a producer of NADPH and can help make up for that deficiency – in liver.

Question 17

what is the function of Malonyl CoA?

Answer 17

primarily for FA synthesis, so once here the pathway is committed to FA synthesis

Question 18

what is palmitate derived from in relation to fatty acid synthase complex?

Answer 18

malonyl CoA to a growing acyl chain

Question 19

what is fatty acid synthase?

Answer 19

a single multifunctional protein with 7 different enzyme activities in a single polypeptide chain which forms a homodimer

Question 20

what protein cofactor is also needed for the fatty acid synthase complex?

Answer 20

Acyl Carrier Protein (ACP) which contains phosphopantetheine, a prosthetic group very similar to coenzyme A

Question 21

in the fatty acid synthase complex, where does the malonyl CoA attach?

Answer 21

to the -SH on ACP

Question 22

what are the 5 stages in FA synthesis?

Answer 22

loading
condensation
reduction 
dehydration
reduction

Question 23

what does the ACP (Acyl Carrier Protein) do?

Answer 23

it carries the Acyl for the fat

Question 24

T/F, fatty acid synthesis requires Malonyl CoA?

Answer 24

true

Question 25

two main takeaways for FA synthesis?

Answer 25

loading phase through acetyl CoA and then Malonyl CoA used for elongation

Question 26

why is NADPH a critical factor in fatty acid biosynthesis? or what would happen if it is deficient and its effect on fatty acid biosynthesis

Answer 26

trouble making fat
trouble with membranes
trouble with adipose storage

Question 27

how many times does the FA synthesis cycle continue?

Answer 27

this cycle is repeated 7 times forming palmitate (16 carbon chain) which uses malonyl ACP each time

Question 28

in the final reaction of the FA synthesis what happens?

Answer 28

you have the cleavage of palmitoyl ACP by a thioesterase to release the free fatty acid and so palmitate is rapidly converted to palmitoyl CoA by acyl CoA synthetase

Question 29

in terms of elongation of fatty acids besides palmitate like stearate (C18:0) and oleate (18:1) how and where does this happen?

Answer 29

The elongation and desaturation enzymes are localized to the cytoplasmic face of the endoplasmic reticulum

The elongase uses fatty acyl CoA as substrate and extends the chain two carbons at a time using malonyl CoA condensation followed by reduction, dehydration and reduction using NADPH in analogous fashion to FA synthase.

Question 30

since human desaturates can not introduce double bonds in a saturated fat past carbon 10 what positions can they saturated at?

Answer 30

C5, C6 and C9 examples being palmitic acid to palmitoleic acid (16:1, Δ9) and stearic acid to oleic acid (18:1, Δ9)

Question 31

what are the limitations to where humans cannot place double bonds?

Answer 31

between carbon 10 and the ω-carbon (terminal methyl group)

Question 32

what is an important precursor for the production of arachidonic acid?

Answer 32

linoleic acid and so this can be modified through use of desaturase and elongation to produce the arachidonic acid