Lipid Metabolism: FA Synthesis

Question 1

What are the functions of lipids?

Answer 1

They provide:

• fuel stores
• structural components for LIPID MEMBRANE
• signaling molecules for transduction pathways for growth)

Question 2

What are the FA derivatives?

Answer 2

glycerolipids, glycerophospholipids, sphingophospholipids

Question 3

What is the major source for FA synthesis and why?

Answer 3

Dietary carbohydrates are the largest source for FA synthesis because of its ability to upregulate the transcription of proteins for FA synthesis through INSULIN RELEASE

Question 4

Where does FA synthesis occur for the most part?

Answer 4

In the liver

Secondarily: adipose tissue, brain, kidney, mammary glands

Question 5

What are the overall steps in FA synthesis?

Answer 5

1. ) Cytosolic entry of Acetyl-CoA
2. ) Generation of Malonyl-CoA
3. ) FA Chain formation (7 Rxns via FA Synthase)

Question 6

What is the rate-limiting step of FA synthesis?

Answer 6

Acetyl CoA Carboxylase–> the carboxylation of acetyl-CoA to Malonyl CoA

Question 7

What are the key regulators of the rate-limiting step for Acetyl CoA Carboxylase?

Answer 7

(+) CITRATE, INSULIN

(-) GLUCAGON, EPINEPHERINE, PUFA, HIGH AMP, PALMITATE

Question 8

Is Acetyl CoA Carboxylase (anabolic state) phosphorylated or not phosphorylated to be activated?

Answer 8

De-phosphorylated

Question 9

What does ATP Citrate Lyase do? What are the regulators of it?

Answer 9

ATP Citrate lyase splits citrate–> OAA + Acetyl-CoA

Regulators:
(+) glucose, insulin
(-) PUFA, Leptin**

Question 10

What happens to OAA after ATP Citrate Lyase splits Citrate?

Answer 10

OAA will become Malate:

Malate–> OAA (Malate Dehydrogenase) (malate-kg-transporter)
Malate–> Pyruvate + NADPH (Malic Enzyme)

Question 11

Where is the NADPH produced from?

Answer 11

It is produced from the:
Pentose Phosphate Pathway (2-12 NADPH produced)
Malic Enzyme (converts Malate–> Pyruvate) (1 NADPH)

NADPH necessary for FA Synthase activity

Question 12

What are the substrates for Acetyl CoA Carboxylase?

Answer 12

CO2, ATP, Biotin

Question 13

Random but IMPORTANT: Is Malonyl CoA an inhibitor or activator of the rate-limiting enzyme in FA degradation- Carntitine Acyl Transferase I/ Carnitine Palmitoyl Transferase I?

Answer 13

**INHIBITOR

Question 14

Describe the structure of FA Synthase Complex

Answer 14

Multi Enzyme Complex:

• 2 identical dimers
• 7 enzymes/ dimer
• Acyl Carrier Proteins

Question 15

FA Synthesis Stoichiometry

Answer 15

1 Acetyl CoA + 7 Malonyl CoA + 14NADPH + 14 H+ –> Palmitic Acid + 14 NADPH+ + 8CoA + 6H20

Question 16

FA Synthase- overall rxn flow

Answer 16

1. ) condensation
2. ) reduction
3. ) dehydration
4. ) reduction

Question 17

What does Leptin do? What structural part of the body does it regulate? How does it regulate?

Answer 17

Leptin is a hormone released from the adipocytes that gives signals to the hypothalamus on the levels of fat storage. It regulates the satiety as well as FA synthase–> decreases FA Synthesis.

Question 18

How are FAs longer than 16 chains made?

Answer 18

They are created in the mitochondria or Smooth Endoplasmic Reticulum

Question 19

For longer chain FA synthesis, past 16-Chains, what compound is used for SER vs. Mitochondria?

Answer 19

SER- Malonyl CoA

Mitocondria- Acetyl CoA

Question 20

Where does desaturation of FAs occur? What are the limitations of the human metabolism for FA Desaturation?
Which enzymes do we have?

Answer 20

FA Desaturation occurs:
Smooth Endoplasmic Reticulum

Human limitations: Can’t go past C-9
Acyl CoA Desaturases of Humans: 4,5,6 and 9