Exam 4 L1: Lipid Metabolism

Question 1

Explain what happens in the fed state to the rate limiting enzymes of lipid metabolism

Answer 1

Fed State: INSULIN

Activate Acetyl CoA Carboxylase (turning acetyl coA into Fatty Acyl-coA… eventually making TAGs)

Inhibit Carnitine Palmitoyltransferase I

Increase production of cholesterols from acetyl coA

Question 2

Explain what happens to the rate limiting enzymes in lipid metabolism during the fasted state

Answer 2

Fasting State: EPI

Activates carnitine palmitoytransferase I (which takes fatty acyl-coAs and transports them into mitochondria where they are turned into acetyl coA)

Then HMG-CoA synthase is activated to turn the acetyl coA into ketone bodies (for brain functions)

Question 3

During the fed state:

Fatty acids are transported as part of ___ or ____

Answer 3

During the fed state:

dietary TAGs are packaged as chylomicrons in the small intestine and enter the blood stream

synthesized TAGs enter the blood stream after being turned into “low density lipoproteins” in the liver

Question 4

During the fasted state:

FAs are transported bound to ____

Answer 4

During the fasted state,

FAs are transported bound to albumin

TAGs are mobilized as fatty acids in the blood stream as “free fatty acids” but are essentially bound to albumin

Then the liver can make ketone bodies to supply energy for the brain

Question 5

What fatty acid is the product of FA synthesis?

Which fatty acids are the omega 3 essential FA’s?

Which fatty acid is a precursor of prostaglandin?

Answer 5

Palmitic is the product of FA synthesis

Linoleic and Linolenic are the omega 3 essential FAs

Arachidonic is the precursor of the prostaglandins

Question 6

“Free fatty acids” in the plasma are____-

Answer 6

“Free fatty acids” in the plasma are bound to serum albumin and are circulated in the blood stream

Question 7

The equation for Fatty Acid Biosynthesis:

what is it? (remember, essentially, acetyl coA and malonyl coA are going to Palmitate)

Answer 7

Question 8

Explain the role of Acetyl coA Carboxylase in the DeNovo biosynthesis of fatty acids

Answer 8

Question 9

Fatty acid biosynthesis requires:

1.

2.

3.

4.

5

Answer 9

Fatty acid synthesis requires:

1. acetyl groups - transported by citrate from the mitochondria into the cytoplasm
2. acetyl-coA carboxylase (rate limiting enzyme)
3. biotin - carrier of activated CO2
4. Fatty Acid Synthase Complex
5. NADPH

Question 10

All carbons are derived ultimately from _____

Most ______ derive from _____ metabolism

Answer 10

All carbons are derived ultimately from acetyl coA

Most acetyl-coAs derive from carbohydrate metabolism

Question 11

Citrate:

Stimulates _______ biosynthesis

Transports _____

Allosterically activates _____-

Answer 11

Citrate stimulates fatty acid biosynthesis

Citrate transports acetyl groups from mitochondria

Citrate allosterically activates acetyl coA carboxylase

Question 12

Citrate is the carrier of _____ from the ____ to the ____

Answer 12

Citrate is the carrier of acetyl groups from the mitochondria to the cytoplasm

Question 13

If there is an abundance of citrate, what does that mean?

Answer 13

Abundance of citrate means the TCA cycle is in robust activity, and additional acetyl coA can be converted and ultimately stored as TAGs

Question 14

Explain the citrate shuttle

Answer 14

Essentially, the citrate shuttle transports citrate from the mitochondrial matrix to the cytosol.

Then citrate is used to make acetyl coA and oxaloacetate.

The acetyl coA goes onto Fatty Acid synthesis.

The oxaloacetate is regenerated into pyruvate, and in that process we form NADPH we gets utilized in fatty acid synthesis as well.

Question 15

What is the rate limiting enzyme in Fatty Acid Biosynthesis?

What rxn does that enzyme catalyze?

What is the cofactor for that enzyme?

Answer 15

Acetyl CoA Carboxylase:

• Rate-Limiting Enzyme in Fatty Acid Biosynthesis
• Catalyzes the formation of malonyl-coA from acetyl-coA
• Biotin, a cofactor, serves as a carrier of activated CO2

Question 16

Acetyl coA carboxylase rxn:

Acetyl coA + HCO3- + ATP ———->

Malonyl CoA + H20 + ADP + Pi

What are the activators and inactivators of acetyl CoA carboxylase?

Answer 16

Activators: Citrate and Insulin and Biotin

Inactivators: Palmitoyl CoA (end product inhibition) and Glucagon and Epi (promoting phosphorylation of the enzyme)

Question 17

What is the product of the reaction synthesized by acetyl coA carboxylase?

What is the physiological significance of that product?

Answer 17

Product of acetyl coA carboxylase rxn: Malonyl coA

Malonyl CoA is the only physiological inhibitor of the rate limiting enzyme in fatty acid oxidation (carnitine palmitoyltransferase I)

Malonyl coA is also a key regulator of fatty acid oxidation and ketone body formation

Question 18

Regulation of Acetyl CoA Carboxylase; SHORT TERM

allosteric activator and allosteric inhibitor

hormonal activator and hormonal inhibitor

Answer 18

SHORT TERM regulation of Acetyl coA carboxylase:

allosteric activator: citrate

allosteric inhibitor: palmitoyl coA and AMP

Hormonal activator: insulin (promotes dephosphorylation)

Hormonal inhibitor: glucagon and epi (promotes phosphorylation)

Question 19

LONG TERM regulation of acetyl coA carboxylase:

Increased Enzyme Synthesis due to ….

Decrease Enzyme Synthesis due to….

Answer 19

Long Term Regulation of Acetyl CoA Carboxylase:

Increased Enzyme Synthesis: high carb diet, insulin, thyroid hormone, fat free diet

Decreased Enzyme Synthesis: high fat diet, fasting, glucagon

Question 20

The Fatty Acid Synthase Complex :

catalyzes the formation of ____ from _____

Answer 20

The fatty acid synthase complex:

Catalyzes the formation of fatty acids (e.g. palmitate) from 1 Acetyl-CoA + 7 Malonyl CoA

Question 21

Make sure you know the stoichiometry of the following eqn:

Acetyl CoA (2C’s) + 7 Malonyl CoA (21C’s) + 14 NADPH + 14 H+ ———>

Answer 21

Acetyl CoA (2C’s) + 7 Malonyl-CoA (21 C’s) + 14 NADPH + 14 H+ —————–>

Palmitate (16 C’s) + 7 Co2 + 14 NADP+ + 8 CoA + 6 H20

Question 22

The fatty acid synthase complex catalyzes ____ reaction cycles

Answer 22

Fatty acid synthase complex catalyzes seven reaction cycles (approximately)

Question 23

Name the steps of the fatty acid synthase complex (just give the general name for the steps)

Answer 23

Fatty Acid Synthase Complex Rxns

1. Condensation
2. Reduction
3. Dehydration
4. Reduction

Question 24

Now explain each step in the fatty acid synthase complex

Answer 24

FIRST: acetyl coA gets added to an Acyl carrier protein, and so does malonyl coA to form butyryl ACP and malonate

Then during the condensation rxn: ace

Question 25

What is the product of fatty acid biosynthesis?

What are the fates of that substance?

Answer 25

product of fatty acid biosynthesis: palmitate

Palmitate can then be elongated or desaturated

Ultimately, they are esterified to TAGs, phospholipids, and cholesterols

Question 26

Regulation of the Fatty Acid Synthase Complex:

Short Term:

• Activator is _______

Long Term:

Answer 26

Regulation of FAS Complex:

Short Term:

Allosteric activator is Fructose 1, 6-bisphosphate

Long Term:
Increased E Synthesis: High carb diet, insulin, fat free diet

Decreased E Synthesis: Glucagon, High fat diet, fasting

Question 27

PRARs promote _____

Answer 27

PRARs promote TAG deposition