Lipid Metabolism pt. 2

Question 1

What are the sites of lipid synthesis?

Answer 1

-all tissues synthesize lipids
-qualitatively major sites:
-liver
-adipose tissue
-mammary gland (lactating)

Question 2

Explain the major site in humans; the liver.

Answer 2

-triacylglycerol synthesized from glucose (and fructose)
-most triacylglycerol comes from the diet
-TG synthesized when:
very low fat diet or very high carbohydrate diet
-released by liver as VLDL
-taken up by adipose tissue- lipoprotein lipase

Question 3

Review B-oxidation

Answer 3

-takes place in mitochondria
-two carbon “units” removed as acetyl-CoA from fatty acyl-CoA
-Acetyl-CoA oxidized
-forms NADH and FADH2

Question 4

Is lipid synthesis an opposite of B-oxidation?

Answer 4

No!

Question 5

What are the similarities between FA synthesis and B-oxidation?

Answer 5

-built by addition of 2-carbon units to growing fatty acids
-similar intermediates are formed

Question 6

What are the differences between FA synthesis and B-oxidation?

Answer 6

-FA synthesis is in the cytoplasm
-acetyl-CoA gets out of the mitochondria:
condenses with OAA to form citrate (citrate synthase reaction), then transported out (tricarboxylate carrier) and then is cleaved by citrate lyase
-involves malonyl-CoA, which is a three carbon intermediate not involved in fatty acid oxidation

Question 7

What is acetyl-coA carboxylase?

Answer 7

1st step in fatty acid synthesis from cytoplasmic acetyl-CoA, adds one carbon onto acetyl coA at the expense of 1 ATP to make malonyl-coA

Question 8

What are the two steps of fatty acid synthesis:

Answer 8

7 acetyl-CoA + 7ATP + 7CO2 –> 7 Malonyl-CoA + 7ADP + 7Pi (acetyl-CoA carboxylase)
then:
Acetyl-CoA + 7 malonyl-CoA + 14 NADPH (from PPP) + 14H+ –> palmitate + 7CO2 + 8CoA + 14NADP+ 6H2O
(fatty acid synthase complex)

Question 9

Explain fatty acid synthase,
acyl carrier protein
and use of NADPH

Answer 9

-enzymes of FA synthesis in the form of a multi-enzyme complex
-intermediates are link to them, a component of fatty acid synthase
-the electron donor (oxidation uses NAD+ and FAD as electron acceptors)

Question 10

What is the structure of fatty acid synthase?

Answer 10

-dimer of two 240 kDa proteins (huge)
-function independently
-each consists of 7 enzyme activities and ACP

Question 11

Overview of Fatty acid synthesis.

Answer 11

Starts with 1 acetyl-CoA and malonyl-CoA, releases CO2, double bonds are reduced using NADPH
Gets released once you reach 16 carbons

Question 12

How is acetyl-CoA carboxylase regulated?

Answer 12

-allosteric regulator- citrate
-regulation by : phosphorylation/dephosphorylation
phosphorylated (inactivated) by glucagon, AMPK
dephosphorylated (activated) by insulin (this from polymerizes)

Question 13

How is acetyl-CoA allosterically regulated by citrate?

Answer 13

-dephosphorylated from highly activated with no citrate
-citrate partly overcomes inhibition due to phosphorylation, which will decrease the activity

Question 14

What are the 3 products of eicosanoid synthesis?

Answer 14

-prostaglandins
-thromboxanes
-leukotrienes

Question 15

Explain the actions of anti-inflammatories.

Answer 15

NSAIDS:
-inhibit cyclooxyrgenase
-aspirin covalently, all others are reversible
-decrease prostaglandins and thromboxanes
Steroids (glucocorticoids):
-decrease expression of PLA2 and COX
-decrease leukotrienes

Question 16

What are the 3 precursors for triacylglycerol and phospholipids?

Answer 16

-glycerol 3-phosphate
- fatty acyl-CoA
Phospholipid needs headgroup (serine choline, etholamine)

Question 17

What is a triacylglycerol?

Answer 17

three fatty acids esterfied to a glycerol backbone

Question 18

What is a triacylglycerol?

Answer 18

three fatty acids esterifed to a glycerol backbone

Question 19

What are the two sources of glycerol-3-phosphate?

Answer 19

glycolysis: glycerol 3-phosphate dehydrogenase
glycerol: glycerol kinase

Question 20

How is fatty acyl-CoA formed?

Answer 20

fatty acid + CoASH + ATP –> fatty acyl-CoA + AMP + Phi (fatty acyl-CoA synthetase)

Question 21

How is phosphatidic acid synthesized?

Answer 21

glycerol 3-phosphate + 2 fatty acyl-CoAs –> diacylglycerol 3- phosphate + 2 CoASHs
-diacylglycerol 3-phophate is more commonly called phosphatidic acid

Question 22

Explain phosphatidic acid in lipid synthesis.

Answer 22

Phosphatidic acid:
Attachment of head groups make phospholipids
Phosphatidic acid phosphatase removes a phosphate group, creating diacylglycerol, with acyl transferase and another fatty acyl-CoA can become a triacylglycerol

Question 23

Go over cholesterol synthesis mechanism in notes

Answer 23

done

Question 24

What is a statin?

Answer 24

inhibit HMG-CoA reductase, prevent heart attacks and lower cholesterol

Question 25

What is progesterone synthesis?

Answer 25

-precursor for all steroids
-cholesterol is a precursor for steroid synthesis and bile acid synthesis

Question 26

What is cholestyramine and how does it work?

Answer 26

-first drug shown to lower cholesterol
-binds to bile acids
-increases bile acid excretion
-increases conversion of cholesterol to bile acids which lowers the amount of circulating cholesterol