Lipid Metabolism

Question 1

What kind of synthesis uses acetyl-coA to build up fatty acids?

Answer 1

De novo fatty acid synthesis

Question 2

Where does fatty acid synthesis occur?

Answer 2

in the cytoplasm while acetyl-coA is in the mitochondria

Question 3

How is Acetyl-coA shuttled out of the mitochondria?

Answer 3

through citrate

Question 4

Fatty acid synthesis:
starts with what, which adds...
where does it occur?
What molecule does it use?
hows it regulated?

Answer 4

Starts with acetyl-coA that adds 2C units to a growing fatty acid chain. Happens in liver and adipose. Uses NADPH. Regulated by acteyl-coA carboxylase.

Question 5

What is fatty acid synthesis regulated by and how does it work?
How is it activated?
How is it deactivated?

Answer 5

Regulated by acetyl-CoA carboxylase.
Deactivated by phosphorylation by AMP activated kinase or glucagon signaling (low energy situation) or epinephrine signaling (high energy mobility situation).
Activated by high (citrate) and by dephosphorylation by insulin signaling (high energy situation)

Question 6

How are triglycerides synthesized and why?

Where does glycerol come from and what is it reduced to?

Answer 6

fatty acids > triglycerides for storage. Glycerol comes from glycolysis dehidroxyacetone phosphate which is reduced to glycerol-3-phosphate. 3 fatty acids added in a stepwise fashion to position 1, 2, then 3.

Question 7

If the process of triglyceride synthesis stopped after adding position two, what would happen?

Answer 7

Diaglycerol phosphate would be produced and can be used for membrane lipid synthesis.

Question 8

where does triglyceride synthesis occur? What are they stored in and how are they transported out to the rest of the body, as what compound?

Answer 8

happens in liver and adipose. stored in adipose and in liver it is transported ot the rest of the body by very low density lipoprotein (VLDL)

Question 9

Lipolysis step 0a
What is important about this?
How is it regulated and what is it called?

Answer 9

hormone sensitive lipase/monoacyglycerol lipase - main control point, regulated by insulin and epinephrine.

Question 10

Lipolysis step 0b
Name?
Wheres it occur?
What cant cross mitochondrial membrane and how do we get it into mitochondria?

Answer 10

fatty acyl CoA synthetase
activation reactions happen in the cytosol but further happen in mitochondria.
Fatty acyl CoA cant cross mitochondria, we use the Carnitine shuttle.

Question 11

How does the carnitine shuttle work?

Answer 11

take CoA and put it on a carnitine which is able to go through translocase (pulls fatty acid into mitochondria). Translocase shuttles fatty acids in and free carnitines back out so It can grab another fatty acid and bring it in.

Question 12

Lipolysis step 1Whats it called?
What occurs here?
Where is fatty acyl-coA located?

Answer 12

Acyl-coA DehydrogenaseBeta oxidation - need to oxidize the molecule twice so we use FAD, a double bond type of oxidation. In mitochondria

Question 13

Lipolysis step 2
What is it called?
What happens when we add water?

Answer 13

Enoyl-coA HydrataseWhen we add water, We have oxidized the carbon so we get a reduced molecule of FADH2.

Question 14

lipolysis step 3

Answer 14

3-hydroxyacyl-coA dehydrogenase

Question 15

lipolysis step 4

Products go where?

Answer 15

Thiolase

Back to step one, to TCA cycle, and to ketone bodies

Question 16

Lipolysis/Lipogenesis control

What is the function of Citrate?

Answer 16

Feed forward regulation of ACC - high energy

Goes towards Lipogenesis

Question 17

Lipolysis/Lipogenesis control
What is the function of AMP?
What is ACC?

Answer 17

Activates AMP - activated protein Kinase phosphorylation activates HSL, inhibits ACC, low energy
Goes towards Lipolysis

Question 18

Lipolysis/Lipogenesis control

What is the function of Insulin?

Answer 18

Activates protein phosphatase 2A
Dephosphorylation inhibits HSL, activates ACC
Goes towards lipogenesis

Question 19

Lipolysis/Lipogenesis control

Function of Epinephrine?

Answer 19

Activates Protein Kinase A, phosphorylation activates HSL, inhibits ACC
Goes towards Lipolysis

Question 20

Lipolysis/Lipogenesis control
function of Glucagon?

Answer 20

Activates protein kinase A
phosphorylation activates HSL, inhibits ACC
Goes towards Lipolysis

Question 21

Lipolysis/Lipogenesis control
Function of Malonyl-coA
What does it prevent?

Answer 21

Feed forward regulation of ACC (lipogenesis) blocks CPT1, prevents both sides from being active at the same time

Question 22

What is the problem we will see if all we have is Acetyl-CoA if TCA cycle doesn’t run fast enough?

Answer 22

Using up free CoA to get Acetyl CoA so every time we complete one of these steps we get a free co A that gets added to get acetyl Co A. The TCA cycle is what gets out free CoA back. If we don’t have oxygen, TCA cycle will be messed up. CoA is also used in lipid synthesis.
We need to have sufficient oxygen and glucose.

Question 23

Acetyl-CoA oxidation requires glucose

If we have low glucose, what happens to Acetyl-CoA?

Answer 23

Run out of glycogen > start gluconeogenesis (oxaloacetate drops bc gluconeogenesis doesnt replish it, TCA does), wont deplete it much bc we have gluconeogenic AA so we will use oxaloacetate but also produce it so the TCA cycle can run, can still get free coA back

Question 24

What happens if we have very low glucose level?

Answer 24

run out of gluconeogenic substrates so we will shift to gluconeogenesis, we run out of oxaloacetate and the TCA cycle stops so we no longer get free coenzyme A back.

Question 25

When are ketone bodies formed?

Answer 25

When oxaloacetate/free HS-coA have been depleted.

Question 26

What uses up oxaloacetate?

Answer 26

gluconeogenesis

Question 27

Free HS CoA is used up when utilizing what?

Answer 27

used up by utilizing fat or ketogenic AA

Question 28

What does ketogenesis regenerate and what tissues does it supply energy to?

Answer 28

Regenerates free HS-coA and supplies energy to tissues, especially the heart and brain through ketone bodies

Question 29

What happens if we cant get free conenzyme A back?

Answer 29

start building up acetyl-CoA so glycolysis, beta oxidation, and oxaloacetate production is turned off. As ketone bodies build up in the system, we will get ketosis and then keto acidosis (dropping pH of the blood). If TCA cycle turns off, this is the only way to get our free Co enzyme A back.

Question 30

What is used as an energy source when glucose is very low?

Answer 30

Ketone bodies

Question 31

How are ketone bodies produced?

Answer 31

liver oxidizes fatty acids which produces ketone bodies as long as those tissues have enough glucose left

Question 32

why dont we just use fatty acids as energy source?

Answer 32

They cant get across the blood brain barrier

Question 33

Normal ketone body serum vs ketosis serum

Answer 33

0.1 mM vs greater than 0.5mM

Question 34

What balances production as ketone production increases?

Answer 34

ketonuria

Question 35

What increases due to ketone production becoming dysregulated

Answer 35

ketone serum concentration can raise significantly leading to acidosis

Question 36

What does ketoacidosis lead to?

Answer 36

reduced serum pH (<7.35) and can be measured by significant ketouria

Question 37

7 y/o beagle with polyuria, and weight loss
Renal Glucose is 300 mg/dl and renal ketone bodies are greater than 3 mM
What is the diagnosis?

Answer 37

Diabetes mellitus two
Oxidation of acetyl-CoA requires sufficient gluconeogenic substrates to keep oxaloacetate in the liver high enough. In diabetes mellitus, there is plenty (too much) of glucose around but it cant get into cells. Cells react as though they are starving and burn stored fat producing ketone bodies.