Lipid Metabolism II

Question 1

Describe the energy storage of the body

Answer 1

• blood has 40 Kcal of glucose
• 600 Kcal of glycogen in the liver and muscle
• 24,000 kCal of protein in the muscle
• 100,000 kCal in TAGs

TAGS have 6.75 times as much energy as carbs (glycogen)

Question 2

Describe the structure of Triacylglycerol including the various sources of TAGs

Answer 2

Glycerol backbone with 3 fatty acid chains.

can get TAGs from diet (from intestinal cells)
De novo TAG in both hepatocytes and adipocytes

Question 3

Describe the mobilization of fatty acids from adipocytes in detail (Hunger phase)

Answer 3

In a state of hunger, glucagon and epinephrine are released and go to stimulate a GPCR which leads to a release of cAMP from adenylate cyclase, activating Protein kinase A.

Protein kinase A activates Perilipin via phosphorylation which activates ATGL(adipose triglyceride lipase) that takes the TAG to a DAG

Protein kinase A is also able to phosphorylates HSL (hormone sensitive lipase) that takes the DAG to MAG

MAG lipase takes the MAG to a glycerol and fatty acid form

Question 4

Describe the mobilization of fatty acids from adipocytes in a fed state.

Answer 4

In a fed state, you are getting your fatty acids from your diet so you do not need to make any more. SOOO the insulin receptor triggers the protein phosphatase which dephosphorylates and inactivates HSL Which does not allow the DAGs to get to the MAGs

Question 5

What is a perilipin

Answer 5

family of proteins that coat lipid droplets in adipocytes and muscle cells

This coating helps to regulate the amount of lipid breakdown molecules get in due to decreased physical access

Question 6

How are perilipins regulated?

Answer 6

regulated by PKA that phosphorylates HSL that promotes lipolysis

Question 7

What happens if there is an over expression of perilipin 1? What about a knock out?

Answer 7

Overexpression inhibits lipolysis and the knockout does not inhibit

Question 8

Describe the permeability of the outer and inner mitochondrial membranes

Answer 8

Outer membrane is NOT permeable to fatty acids

Inner membrane is NOT permeable to FaCoA

Question 9

Briefly describe the phases of Fatty acid breakdown including the locations

Answer 9

Phase 1 is the activation of fatty acids and occurs in the cytosol

Phase II is Beta oxidation and occurs in the matrix

Question 10

Describe phase I of fatty acid activation

Answer 10

First reaction in any FA metabolism and occurs INSIDE The cytoplasm

Uses Acyl CoA synthetase

Traps fatty acids in the cells

Makes it metabolically active

Is irreversible because of PPi hydrolysis

Question 11

Describe the translocation into the mitochondrial matrix

Answer 11

Carnitine is able to go the the cytoplasmic side where Acyl CoA acts with carnitine acyltransferase I to make acyl carnitine

acyl carnitine is able to translocate through to the matrix and carnitine acyltransferase II is able to spit out an Acyl CoA with the help of CoA

Question 12

Describe phase II of lipid breakdown

Answer 12

Beta oxidation phase has 4 steps

1. oxidation via the acyl CoA dehydrogenase (ACAD)
2. Hydration via the enoyl CoA hydratase
3. Oxidation via 3-hydroxyacyl CoA dehydrogenase
4. Thiolysis via Acetyl CoA Acetyltranferase

This repeats until the entire fatty acid is broken down

Question 13

What is the function of ACAD

Answer 13

Acyl CoA dehydrogenase is involved in the first step of beta oxidation and oxidizes the beta carbon to produce FADH2 and trans-enoyl-CoA. FADH2 enters the ETC to generate 2 ATP

Question 14

What is the function of enoyl CoA hydrates?

Answer 14

Involved in the second step of B oxidation

Uses water to saturate the alkene to form B hydroxy acyl CoA

Question 15

What is the function of B hydroxy acyl CoA dehydrogenase?

Answer 15

Involved in the third step of B oxidation and oxidizes carbon to form ketoacyl CoA and NADH which is able to enter the ETC to generate 3 ATP

Question 16

What is the function of acyl CoA acyl transferase (ketothiolase)

Answer 16

involved in the fourth step of beta oxidation and attaches a sulfur of the coA to a ketone formed from cleavage of acetyl CoA from fatty acyl chain which is shortened by 2 C’s.

Question 17

Describe what the 4 main steps generate

Answer 17

FIRST(step): ACAD that oxidizes the fatty acid releases FADH2 that takes the electrons to the CoQ enzyme of the ETC

THIRD: B hydroxy acyl CoA dehydrogenase releases NADH during its oxidation reaction. The NADH delivers its electrons to Complex 1 of the ETC

FOURTH: acetyl CoA is released which is able to enter the TCA cycle

Question 18

Given that the number of reaction cycles that are required in order to break down palmitic acid in Beta oxidation,,
What is the amount of ATP that would be gained from
1. FADH2
2. NADH
3. Acetyl CoA
Total ATP and the net ATP

Answer 18

• 2 ATP are formed from FADH2
• 3 ATP are formed from NADH
• 8 acetyl CoA are formed (because two are made in the seventh step; 6+2=8)

FADH2 yields 14 ATP 
NADH yields 21 ATP 
Acetyl CoA yields 96 ATP 
Total is 131 ATP but w ATP are used in the activation of palmitate, which means 
NET= 129

Question 19

Describe the links that are present between lipid and carbohydrate oxidation

Answer 19

1. acetyl CoA is formed from the fatty acids enters the TCA cycle
2. Acetyl CoA combines with OAA to form citrate BUT if the level of carbs is low, then the level of OAA will also be low
   - “Fats burn in the flame of carbohydrates”

Question 20

Describe what happens to excess unused acetyl CoA

Answer 20

condenses to form ketone bodies

Question 21

Who are ketone bodies?

Answer 21

Water soluble and acidic compounds that are produced only in the liver
-provide energy for peripheral tissues during fasting and brain during starvation

Question 22

Describe what happens to the body during fasting and starvation

Answer 22

Fatty acids will be broken down and increase the amount of acetyl CoA that will be able to go to the TCA cycle and the fatty acid derivatives can be used to make ketone bodies that provide energy for the rest of the body during times of fasting and starvation

Question 23

Describe the formation of ketone bodies in detail

Answer 23

two acetyl CoA molecules combine to make acetoacetyl CoA

Another acetyl CoA is added to form 3-hydroxy-3-methyl-glutaryl CoA with the help of water

acetyl CoA is removed to form acetoacetate

acetoacetate is broken down into acetone and D-3-hydroxy-butyrate (this step oxidizes NADH to NAD+)

Question 24

Describe how 2 acetyl CoA are able to be derived from acetoacetate

Answer 24

CoA transferase takes Acetoacetate to acetoacetyl CoA with the help of succinylcholine CoA (yields succinate)

Thiolase adds another CoA to create 2 acetyl CoA molecules

Question 25

Describe the connection of the various pathways (fatty acid synthesis and degradation and the CAC) between various cells in the body

Answer 25

Fat cells take their TAGs to form glycerol and fatty acids.

These are able to travel through the blood from the fat cells and into the liver. The glycerol is able to be taken into glucose and back into the blood. The fatty acids are changed into acetyl CoA which can be made into ketone bodies.

These ketone bodies and the glucose can travel through the blood and to the cardiac muscle, renal cortex, and brain where it is made into acetyl CoA and into the CAC to make CO2 and H20

Question 26

Describe Diabetic Ketoacidosis

Answer 26

Glucose is not able to get into the liver or adipose tissue so the OAA levels drop and CAC slows which releases fatty acids to form ketone bodies.

The blood PH drops (because ketone bodies are acidic)

Coma and death result