Lipid Metabolism

Question 1

The major source of carbon for fatty acid synthesis is dietary _______

Answer 1

Carbohydrates

Question 2

Where does fatty acid synthesis primarily occur? Where else can it occur?

Answer 2

Primarily in the liver

Can also occur in adipose tissue, brain, and kidneys

Question 3

TF: Fatty acid synthesis requires coordination between cytosolic and mitochondrial reactions

Answer 3

TRUE

This is because fatty acids are activated in the cytosol and must be transported into the mitochondria by being converted to fatty acyl CoA and fatty acyl carnitine.

Question 4

What molecule is used as the precursor for fatty acid synthesis?

Answer 4

Acetyl-CoA (a 2 carbon molecule)

Question 5

What are the 3 main phases of fatty acid synthesis? Make sure to note which enzymes are in each phase

Answer 5

Phase I: Cytosolic entry of acetyl coA via ATP Citrate Lyase- made in the mito matrix but needed in the cytoplasm

Phase II: Generation of Malonyl CoA via Acetyl CoA Carboxylase- RATE LIMITING!
-acetyl coA is carboxylated to malonyl coA. Most important substrate in FA synthesis.

Phase III: Fatty Acid Chain Formation via Fatty Acid Synthase- Fatty acid synthase catalyzes 7 reactions that incorporate Acetyl Coa and malonyl Coa into palmitate, the 16 carbon fatty acid.

Question 6

Which molecule from the TCA cycle can be used in the synthesis of fatty acids?

Answer 6

Citrate

Note Acetyl CoA can as well

Question 7

During fatty acid synthesis, oxaloacetate and acetyl coA combine to form citrate within the mitochondria. Citrate then leaves the mitochondria and is broken back into oxaloacetate and acetyl coA by what enzyme?

Answer 7

ATP Citrate Lyase

Question 8

During fatty acid synthesis, acetyl coa is now in the cytosol and is turned into malonyl coA by what enzyme? What is important about this part of fatty acid synthesis?

Answer 8

Acetyl CoA Carboxylase converts Acetyl CoA into Malonyl CoA in the cytoplasm

This is the rate limiting step

Question 9

What is Malonyl CoA used for in fatty acid synthesis?

What is important about Malonyl coA in terms of regulation of fatty acid metabolism?

Answer 9

It is a substrate for Fatty Acid Synthase

It also prevents FA synthesis and degradation from occurring simultaneously by inhibiting the Carnitine Acyltransferase enzyme (which is the rate limiting enzyme for FA degradation)

Question 10

Describe the protein Fatty Acid Synthase in terms of its composition.

Answer 10

It is a large enzyme that has 2 identical dimers that are arranged in a head to tail fashion.

Question 11

What molecule is required from the PPP in order for fatty acid synthesis to occur?

Answer 11

NADPH, note that we need 14 of these to make a 16 carbon fatty acid (2 NADPH for every 2 carbons added)

Question 12

What are the 2 sources of NADPH?

Answer 12

Malic enzyme: gives 1 molecule of NADPH when it converts malate to pyruvate

PPP: 12 molecules of NADPH

Question 13

What are the 3 most important enzymes found in Fatty Acid Synthesis?

Answer 13

1. ATP Citrate Lyase (phase I)
2. Acetyl CoA Carboxylase (phase II)
3. Fatty Acid Synthase (phase III)

Question 14

What are the 2 allosteric regulators of Acetyl CoA Carboxylase and which increases its function and which decreases it?

Answer 14

Citrate (+)

Long Chain Fatty Acids (Ex. Palmitate) (-)

Question 15

What are the 4 phosphorylating/Dephosphorylating factors that affect Acetyl CoA Carboxylase? Which are activating and which are inhibiting?

Answer 15

Phosphorylating (Inhibits):
Epinephrine (-)
Glucagon (-)
AMP (-)

Dephosphorylating (+):
Insulin (+)- by activating protein phosphatase

Question 16

What type of diet would upregulate Acetyl CoA Carboxylase? *Hint: remember that this enzyme is the rate limiting enzyme used to make fatty acids and essentially store fat

Answer 16

A high carb, low fat diety

Question 17

During Fatty Acid Synthesis, fatty acid synthase lengthens the fatty acid chain. The Smooth endoplasmic reticulum and Mitochondria have different carbon donors for this chain. What are the carbon donors for each?

Answer 17

Smooth Endoplasmic Reticulum uses Malonyl CoA as a carbon donor

Mitochondria uses Acetyl CoA as a carbon donor

Question 18

What enzyme is used to desaturate (make double bonds) in fatty acids? Where does this occur?

Answer 18

Acyl CoA Desaturases

Only occurs in the SER

Question 19

What are the 4 desaturases humans have? This means that fatty acids with double bonds beyond carbon __ and ___ cannot be synthesized in humans.

Answer 19

∆4, ∆5, ∆6, and ∆9

Humans cannot synthesize double bonds beyond carbons 9 and 10

Question 20

Humans ingest w-3 and w-6 fatty acids in order to meet their dietary needs. What is the main w-3 and w-6 precursors we ingest?

Answer 20

Linolenic Acid (w-3) *longer word is w-3
Linoleic Acid (w-6) *shorter word is w-6

Question 21

What are Linolenic and Linoleic used as precursors to make?

Answer 21

Linolenic (w-3) is used to make Eicosapentanoic acid (EPA) and Docosahexanoic acid (DHA)

Linoleic (w-6) is used to make Arachidnonic Acid- the precursor for prostaglandins, leukotrienes, and thromboxane

Question 22

Pound for pound, TAGS contain about _____ times as much energy as carbs

Answer 22

6.75

Question 23

How man calories are found in TAGS? How many in glucose?

Answer 23

100,000 calories

40 in glucose

Question 24

What is the order in which our body will degrade our macromolecules?

Answer 24

Carbs- checking account
TAGs- savings account
Proteins- 401K (Do not touch unless absolutely needed)

Question 25

Where is glycerol kinase found?

Answer 25

It is the only found in the liver during fatty acid synthesis into DAGs anbd TAGs

Question 26

Compare and contrast TAG synthesis in the liver and in adipose tissue.

Answer 26

Liver:
Glucose and Acetyl coA are both used to form DAGs and TAGs, which form VLDL, which is transported in the blood to adipose tissue

Adipose Tissue:
Receives chylomicron VLDL and breaks it down to fatty acids and reforms TAGs for storage in adipose tissue.
*Note that insulin upregulates this process

Question 27

What are the 3 main lipases used to breakdown TAGs?

Answer 27

Hormone Sensitive Lipase (HSL)
Lipoprotein Lipase (LPL)
Monoacylglycerol Lipase (MAG Lipase)

Question 28

Describe the function of Glucagon and Epinephrine during hunger and exercise in terms of how they affect fatty acid mobilization from adipocytes.

Answer 28

Glucagon and Epinephrine stimulate GPCR, which activates Adenylate cyclase. This increases cAMP which activates Protein Kinase A, which phosphorylates Perilipin to activate it. Perilipin activates Hormone Sensitive Lipase, which degrades DAGs into fatty acids.

Question 29

Describe the function of Insulin during the fed state in terms of how they affect fatty acid mobilization from adipocytes.

Answer 29

Insulin activates the RTK receptor, which activates protein phosphatase, which dephosphorylates and inactivates Hormone Sensitive Lipase, therefore preventing the breakdown of TAGs/DAGs

Question 30

What is the function of Perilipin?

Answer 30

To inhibit lipolysis AKA breakdown of fat. This is a target for obesity treatment since if you knock this out it is extremely easy to lose weight.

Question 31

Once fatty acids are translocated into the mitochondria, what are they used for?

Answer 31

Beta Oxidation to generate:
Acetyl CoA
FADH2
NADH

Question 32

What are the 4 stages of beta-oxidation?

Answer 32

Oxidation- Acyl CoA Dehydrogenase (ACAD)- forms FADH2
Hydration
Oxidation
Thiolysis

Question 33

What are the 4 types of ACADs? Which one is mostly associated with inherited defects?

Answer 33

Short, medium, long, very long chain Acyl CoA Dehydrogenase

Medium Acyl CoA Dehydrogenase (MCAD)

Question 34

How do peroxisomes utilize fatty acids?

Answer 34

Use fatty acids to make hydrogen peroxide (H2O2)

Question 35

What are 3 molecules that give rise to ketone bodies? Where are they produced?

Answer 35

Acetoacetate
Beta-Hydroxybutyrate
Acetone

Produced in the liver only