Chapter 28 & 29- Lipid Biosynthesis

Question 1

What is fatty acid biosynthesis?
What enzyme does it?
How does it stop

Answer 1

Occurs in cytosol
Requires multiple biochemical reactions
FA are synthesized by a multienzyme complex
Fatty acid synthase (FAS) does this
FA chain length is increased by addition of 2 carbon units derive from acetyl CoA

Elongation stops with formation of palmitate

Slide 2-3

Question 2

What is the citrate shuttle?

Answer 2

Slide 4
Going from mitochondrion to cytoplasm
Citrate crosses membranes then turns to oxaloacetate then to malate then pyruvate then cross the membrane to mitochondria and convert to oxaloacetate

Question 3

In FA biosynthesis, what does acetyl CoA carboxylase catalyze?

Answer 3

Acetyl CoA carboxylase catalyzes the first and rate limiting step of FA biosynthesis

Slide 5

Question 4

What is the structure of fatty acid synthase?

Answer 4

Slide 6
ACP- Acyl Carrier Protein (tethers the growing fatty acid chain to Fatty acid synthase)
Acetyl CoA 
Malonyl CoA
Palmitate

Multifunctional enzyme complex

Question 5

How do you load fatty acid synthase with the substrates acetyl CoA and malonyl CoA?
Slides 7-8

Answer 5

Acetyl CoA- uses acetyl transacase (AT) to produce β-ketoacyl synthase or acetyl

Malonyl CoA- uses malonyl transacetylase (MT) to produce malonyl-ACP

Question 6

What are the 5 steps using fatty acid synthase to create 2 carbons?
Their enzymes?
Slides 9-13

Answer 6

1. Condensation- β-ketoacyl synthase (KS)
2. Reduction- β-ketoacyl reductase (KR)
3. Dehydration- β-hydroxyacyl dehydratase (HD)
4. Reduction- enoyl reductase (ER)
5. Translocation- Acetyl transacylase (AT)

Question 7

How do you start round two of fatty acid biosynthesis with fatty acid synthase from carbons 4 to 6?

Answer 7

Malonyl CoA -> malonyl-ACP (priming reaction) catalyzes by malonyl transacylase (MT)
Condensation (KS)- butyryl group is condensed to malonyl ACP

Then repeat:
Reduction
Dehydration
Reduction
Translocation

End with 6 carbon fatty acid

Question 8

What is palmitate and how does it group from fatty acid biosynthesis?

Answer 8

Free palmitate is released from fatty acid synthase complex (ACP) by hydrolysis
ACP-palmitate + H2O -> free palmitate

Slide 15-16

Question 9

Where does elongation of fatty acids occur?

Answer 9

Endoplasmic reticulum

Adds 2 carbons at a time

Question 10

What is fatty acid desaturation?

Answer 10

Introduction of cis double bonds
Catalyzed by desaturase enzymes

Location of double bind is specific for each desaturase

Slide 18

Question 11

What two desaturases do humans lack?

Answer 11

Humans lack Δ12 and Δ15
Therefore linoleate and α-linolenate are considered essential fatty acids and must be consumed in the diet
(Our body cannot synthesize them and we need the desaturases)

Slide 19

Question 12

What is cholesterol synthesis?

Answer 12

Synthesized mainly by the liver

Functions:
Structural component of membranes
Precursor of bile salts, steroid hormones, & vitamin D

27 carbons, all C-atoms of cholesterol come from acetyl CoA
Synthesized in the cytosol and ER

Slide 20-21

Question 13

What are the four stages of the synthesis of cholesterol?

Answer 13

3 acetyl CoA -> mevalonate (occurs in cytosol and ER) slide 23
Mevalonate -> activated isoprene
Activated isoprene -> squalene
Squalene -> cholesterol

Slide 22

Question 14

What are the 2 fates of cholesterol?

How is it transported?

Answer 14

Primarily synthesized in liver, then,

Hepatocyte plasma membrane
Or
Exported from blood to tissues
Slide 24

Cholesterol is transported by lipoproteins (complexes of proteins and lipids) they also carry triacylglycerol
Slide 25

Question 15

Out of chylomicrons, very low density lipoproteins (VLDL), Leo density lipoproteins (LDL), and high density lipoproteins (HDL), which ones carry triacylglycerols and which carry cholesterol?

Answer 15

Transport triacylglycerols- chylomicrons and VLDL

Transport cholesterol- LDL and HDL

Slide 26

Question 16

How is cholesterol synthesis regulated?

Answer 16

Balance between synthesis and dietary uptake

Regulated by intracellular cholesterol levels
HMG-CoA reductase goes up when cholesterol is low

Slides 27-28

Question 17

What is familial hypercholesterolemia?

Answer 17

Very high circulating cholesterol levels
Severe atherosclerosis
Defective LDL receptor
Cholesterol - not cleared from blood -> atherosclerotic plaques

Slides 29-30

Question 18

What is glycerolipid synthesis?

Answer 18

Triacylglycerols and phospholipids are synthesized from a common pathway

Acyltransferase catalyze the sequential attachment of fatty acids to glycerol backbone (ester bond)

Slides 31-33

Question 19

What is the synthesis of phosphatidylcholine?

Answer 19

CDP- choline pathway (all tissues)
Cytidine diphosphate
Slide 34

Methylation pathway (liver)
Can go from phosphatidylethanolamine to phopshatidylcholine or phosphatidylethanolamine to phosphatidylserine by phosphatidylserine synthase

Slide 35-36

Question 20

What is phosphatidylethanolamine synthesized by decarboxylation of phosphatidylserine?

Answer 20

Slide 37

Done by phosphatidylserine decarboxylase