Lipid Lecture

Question 1

Where does synthesis of fatty acids occur?

Answer 1

Liver

Question 2

Where and how are fatty acids stored (summary)?

Answer 2

as triglycerides in adipose tissue

Question 3

What enzyme is integral to the first stage of fatty acid synthesis?

Answer 3

acetyl CoA carboxylase

Question 4

What enzyme is integral to the second stage of fatty acid synthesis?

Answer 4

fatty acid synthase

Question 5

What is required for fatty acid synthesis?

Answer 5

Cytosolic acetyl CoA (exported from mitochondria as citrate) and NADPH (pentose PP and malate to pyruvate reaction)

Question 6

A high insulin/glucagon ratio induces synthesis of:

Answer 6

Pyruvate dehydrogenase,
Malic enzyme,
and citrate lyase

Question 7

The pentose phosphate pathway starts with ____ and creates ____, which is necessary for lipid synthesis.

Answer 7

Glucose-6-phosphate,

NADPH

Question 8

Malic enzyme converts ___ to ___.

Answer 8

Malate to pyruvate

Question 9

Acetyl CoA carboxylase requires ____, which is a B vitamin.

Answer 9

Biotin

Question 10

Acetyl CoA converts ___ to ____.

Answer 10

Acetyl CoA to Malonyl CoA

Question 11

What regulates acetyl CoA carboxylase?

Answer 11

Palmitoyl CoA inhibits, and citrate activates, phosphorylation inactivates
insulin indirectly activates by activating phosphatase

Question 12

Phosphatase is regulated by ___.

Answer 12

insulin activates it

Question 13

The fatty acid synthase complex ___(action)___. It is __#___ protein(s) with # different enzymatic activities and an ______. It is a ____ of identical polypeptides arranged head to tail.

Answer 13

sequentially adds 2 carbon units from malonyl CoA to the growing fatty acid chain.
It is one protein with 7 different enzymatic activities and an acyl-carrier protein
It is a dimer of identical polypeptides arranged from head to tail.

Question 14

After __#__ cycles of synthase activity, a final ________ occurs.

Answer 14

6 cycles of synthase activity precede a final thioesterification to palmitate

Question 15

Components of each cycle of the fatty acid synthase complex

(There is one for the steps and one for the enzymes)
(One of the steps in the cycle is the last in one and first in the other)

Answer 15

1. Condensation
2. Reduction
3. Dehydration
4. Reduction
5. “Scoot over” (Transacetylation)
6. Malonyl Transacylase
7. beta ketoacyl synthase
8. Ketoacyl reductase
9. dehydratase
10. enoyl reductase

Question 16

Acyl groups of FA synthase are transferred as ____ on the ______ residue of _____ or the ___ of a ___ residue.

Answer 16

thioesters,
phosphopantetheinyl,
acyl carrier protein,
-SH,
Cys

Question 17

What is the balanced equation of fatty acid synthesis?

Answer 17

8 acetyl CoA + 7 ATP + 14 NADPH + 14 H+ —> Palmitate + 8 CoASH + 7 ADP + 7 Pi + 14 NADP+

Question 18

What is the difference between fatty acid synthesis and fatty acid oxidation?

Answer 18

Fatty acid synthesis requires ACP as acyl group carrier, NADPH as an electron donor and malonyl-CoA as a 2 carbon donor.
Fatty acid oxidation uses CoA as acyl carrier, FAD and NAD+ as electron acceptors, acetyl-CoA as 2 carbon product

Question 19

What regulated fatty acid synthesis?

Answer 19

Acetyl-CoA carboxylase is activated by citrate and insulin/phosphatase and deactivated through phosphorylation and inhibited by palmitoyl CoA

Fatty acid synthesis is activated by a high insulin/glucagon ratio and transcription factos (USF’s or upstream regulatory factors, SREBPs or sterol response element binding protein, and ChREBP or carbohydrate responsive element binding protein)

Inhibition of carnitine palmitoyltransferase or CPTI by malonyl CoA (prevents simultaneous oxidation and synthesis of fatty acids)

Question 20

Palmitate can be modified to form other FAs through ____.

Answer 20

Elongation, desaturation, formation of triacylglycerol, formation of phospholipids and sphingolipids, and formation of prostaglandins from linoleic acid

Question 21

Where does elongation of fatty acids occur?

Answer 21

In the endoplasmic reticulum (by fatty acid elongase)

Question 22

What is a common product of fatty acid elongation?

Answer 22

Stearic acid

Question 23

What is the difference between the mechanism of elongation and fatty acid synthesis?

Answer 23

The fatty acyl chain is attached to coenzyme A instead of ACP

Question 24

Where does the desaturation of fatty acids occur?

Answer 24

In the endoplasmic reticulum

Question 25

What are the steps of desaturation of fatty acids (by enzyme required)?

Answer 25

1. NADH-cyt b5 Reductase
2. Cytochrome b5
3. Desaturase

Question 26

What is required for the desaturation of fatty acids?

Answer 26

Molecular oxygen, flavoprotein with FAD as a prosthetic group (NADH-cyt b5 reductase), Iron (cytochrome b5, desaturase because active site has iron atoms coordinated to histidine)

Question 27

What are the steps of the synthesis of triacylglycerols?

Answer 27

1. Glycerol from the liver using glycerol kinase and ATP, or glucose to DHAP using NADH
2. Glycerol-3-P
3. Phosphatidate
4. Diacylglycerol
5. Triacylglycerol
6. Blood VLDL in the liver or to adipose stores

Question 28

What are the fates of triacylglycerols?

Answer 28

Adipose stores or blood VLDL if it goes to the liver (using ApoB-100)

Question 29

Insulin stimulates _______ of triglycerides

Answer 29

adipose storage

Question 30

Adipose tissue lacks ____.

Answer 30

glycerol kinase

Question 31

What causes the release of fatty acids from adipose triglycerides?

Answer 31

Phosphorylated hormone sensitive lipase is active and breaks down triacylglycerols in adipose tissue

Question 32

Phospholipid synthesis requires ____ or vitamin __.

Answer 32

Inositol

B8

Question 33

Respiratory distress syndrome occurs when there is failure to __________ in lung surfactant.

Answer 33

to produce enough phosphotidylcholine

Question 34

Draw the pathway for phospholipid synthesis

Answer 34

1 G-3-P + RCO-CoA to R’CO-CoA to phosphatidate and CoA to CDP-diacylglycerol using CTP and releasing PPi to phosphatidyl inositol using inositol and producing CMP

Mechanism II uses a head group (Serine) that reacts with CTP to form CDP-serine then that reacts with diacylglycerol

Question 35

What is the role of phospholipase A2?

Answer 35

It cleaves a C2 fatty acid (that tends to be unsaturated like arachidonate) by phospholipase A2 for prostaglandin synthesis

Question 36

What are sphingolipids used for?

Answer 36

They are important for myeline sheaths on nerve cells and they are the antigenic determinants for the ABO blood group

Question 37

How are sphingolipids formed?

Answer 37

serine and palmitoyl CoA created a sphingosine, which creates ceramid through the addition of fatty acyl to an amino group. Ceramide is converted to sphingomyelin using phosphatidyl choline, which produces diacylglycerol.

Gangliosides and cerebrosides have sugar head groups on ceremide

Question 38

Gangliosides and cerebrosides have _____. (during sphingolipid production)

Answer 38

Sugar head groups on ceremide