Exam 4 L2: TAG Degradation

Question 1

Explain what Glucagon and Epi do overall to lipid metabolism

Think: this means ____ state, so TAGS will be ______

Answer 1

Glucagon and Epi: think fasted state

TAGs will be mobilized into Fatty Acyl-CoA’s by the enzyme HSTL.

Then through beta oxidation, the fatty acyl CoA’s will be turned into Acetyl CoA by carinitine palmitoyltransferase I (rate limiting enzyme).

Then acetyl-coA can be turned into ketone bodies by an enzyme present only in the mitochondria: HMG-COA synthase

Question 2

Triacylglycerols:

• Account for ____ of dietary fat

(Glycerol>>>>> Glucose)

• FAs account for ____ of biologically available energy
• Dietary TAG consumption should be less than ____ total calories
• Most of the TAG-FA’s is ____

Answer 2

TAGs:

Account for 90-95% of dietary fat

FAs account for 95% of biologically available energy

Dietary TAG consumption should be less than 30% of total calories

46% of TAG-FAs is oleic acid (18:1)

Question 3

When there is a need for substrates for energy production (ATP) fatty acids are mobilized from _______

Answer 3

When there is a need for substrates for energy production (ATP) fatty acids are mobilized from adipose tissue TAGs

Question 4

HSTL is activated by ______

_____ is phosphorylated at the same time. This is necessary for HSTL to translocate to the surgace of fat droplet and hydrolyze TAGs

(Explain what HSTL does)

Answer 4

HSTL: activated by cAMP-dependent protein kinase A.

HSTL takes TAGS and clips them into glycerol (which can go to gluconeogenesis) AND Fatty Acids, which become “free fatty acids” within the bloodstream and bind to albumin.

Perilipin is phosphorylated at the same time; this is necessary for HSTL to translocate to surface of fat droplet and hydrolyze TAGs.

Question 5

Explain insulin vs epinephrine’s effects on HSTL

Answer 5

Think about this intuatively

Insulin is an inhibitor of HSTL (we already have enough energy available why would we start to breakdown TAGs)

Epinephrine is an activator of HSTL. We need energy, so we will breakdown TAGs

Question 6

_____ is a major activator of HSTL

____ is also an activator of HSTL

_____ and ____ are permissive. That means they don’t activate the enzyme but their presence is needed for normal function.

______ and ____ inhibit HSTL activity

Answer 6

Epinephrine is a major activator of HSTL

ATCH is also an activator of HSTL

Thyroid hormone and adrenal cortical hormones are permissive.

Prostaglandins (PGE) and insulin inhibit HSTL (called “anti-lipolytic”

Question 7

Fates of the Products of TAG Breakdown:

Released FAs:

• Enter the ____
• Bind to ____
• Are carried to ___
• For ___ and ___

Released glycerol:

• Is transported to the ___ and ___

Glycerol kinase phosphorylates glycerol to glycerol-3-P, which can be used in _____

Answer 7

Fates of the Products of TAG Breakdown:

Released Fatty Acids: Enter the bloodstream, bind to albumin, are carried to muscle, liver, etc, for beta oxidation and energy production

Released Glycerol: is transported to liver and kidney, glycerol kinase phosphorylates it into glycerol-3-P, which can be used in gluconeogenesis

Question 8

Epinephrine ______ HSTL and mobilizes ______ from _____

Answer 8

Epinephrine activates HSTL and mobilizes fatty acids from adipose tissue TAGs

Question 9

Mobilization of Fatty Acids from Adipose Tissue Influences what pathways?

Answer 9

Mobilization of FAs from Adipose TAGs influences:

• Fatty acid oxidation
• Ketone body formation
• Fatty acid biosynthesis
• Glycolysis (muscle)
• Gluconeogenesis (liver)

Question 10

Epinephrine activates HSTL, which then breaks down TAGs into glycerol and FA’s:

What happens to the following processes:

Fatty Acid Biosynthesis

Beta-Oxidation of FA’s

Ketone Body Formation

Glycolysis

Gluconeogenesis

Answer 10

Fatty Acid Biosynthesis: INHIBIT

Beta Oxidation of FA’s : Increased

Ketone Body Formation: Increased

Glycolysis: Inhibit

Gluconeogenesis: Increased

So it inhibits both fatty acid biosynthesis and glycolysis

And it increases beta-oxidation of fatty acids, ketone body formation, and gluconeogenesis

Question 11

Where does Beta-Oxidation of Fatty Acids occur?

Answer 11

Beta-Oxidation of fatty acids occurs in the mitochondria

Question 12

What is the MAJOR energy-producing (ATP-producing) pathway in the body?

Answer 12

Mitochondrial Beta-Oxidation of Fatty Acids

Question 13

What are good users of fatty acids:

1.

2.

3.

4.

Answer 13

Good users of fatty acids:

1. Liver
2. Kidney cortex
3. Heart.
4. Skeletal Muscle

Question 14

Tissues that do not or cannot use FA’s as energy:

1.

2.

3.

4.

5.

Answer 14

RBCs

Brain

Nervous System

Adrenal Medulla

Lens

ALL cannot use FA’s as energy sources

Question 15

Stoichiometry check:

Using 1 Palmitoyl CoA…. how many acetyl coA’s do you synthesize, and how many ATP do you get?

The complete oxidation of palmitate yields ____ ATP

Answer 15

1 Palmitoyl CoA (16 carbon molecule)

uses 7 FAD, 7 NAD+, 7 CoA’s and some water to form

8 Acetyl Co-A’s and 106 ATP’s

Question 16

Each cycle of beta-oxidation generates:

___ Acetyl-CoA

__ NADH

__ FADH2

Answer 16

Each cycle of beta-oxidation generates

1 Acetyl CoA

1 NADH

1 FADH2

Question 17

How do the long chain fatty acids get into the mitochondria for beta oxidation?

Inhibition of this transport results in:

1.

2.

Answer 17

Carnitine transports long chain fatty acids into the mitochondrial matrix for beta-oxidation

Inhibition of this transport results in:
- Inhibition of Fatty Acid Oxidation

• Decreased Production of ATP

Question 18

Explain the functions of CPT-1 and CTP-II

Answer 18

CPT-1: takes fatty acyl group and transports the acyl group onto carnitine within the mitochondria inner layer (making acylcarinitine)

Then, a translocase brings it into the mitochondrial matrix where CPTII can transport the acyl group from acylcarnitine back onto CoASH so that it can undergo beta oxidation

Question 19

What is the only known inhibitor of CPT-1?

Answer 19

The only known inhibitor of CPT-I is malonyl coA

This makes sense because malonyl coA is a sign that fatty acids are being synthesized, so energy is up, you wouldn’t need to break down FA’s for beta oxidation

Question 20

When the liver is actively synthesizing FAs… a concurrent decrease in beta-oxidation is due to…

Answer 20

Inhibition of translocation between cellular compartments

Inhibition of CPT1 by malonyl coA

Question 21

Malonyl coA is the product of the rxn catalyzed by _____, the rate limiting step in FA biosynthesis

Increased Malonyl CoA _____ CPT-I and ____ beta oxidation of fatty acids

Decreased Malonyl CoA ____ fatty acid oxidation

Answer 21

Malonyl CoA is the product of the reaction catalyzed by Acetyl-CoA Carboxylase, the rate limiting enzyme in fatty acid biosynthesis

Increased Malonyl-CoA inhibits CPT-1 and inhibits Beta oxidation of fatty acids

Decreased Malonyl coA increases fatty acid oxidation

Question 22

For Beta Oxidation of Fatty Acids, what are the four general steps?

Answer 22

1. oxidation
2. hydration
3. oxidation
4. cleavage (by the enzyme thiolase)

Question 23

Deficiency of _________ accounts for as much as 10% of sudden infant death syndrome (SIDS)

Answer 23

Deficiency of medium chain FA-CoA dehydrogenase

Question 24

Ketone bodies are formed in the ____ when there is a high rate of ______

Answer 24

Ketone bodies are formed in the liver mitochondria when there is a high rate of beta oxidation of fatty acids

Question 25

Explain how ketone bodies are synthesized from acetyl coA in liver mitochondria

Answer 25

Acetoacetyl-coA plus an acetyl-coA are added together by HMG Co-A Synthase to create HMG-CoA

Then that gets turned into acetoacetate and finally beta-hydroxybutarate

Question 26

Explain what happens during ketone body utilization

Answer 26

Ketone bodies are made in liver, NOT used by liver

In tissues where ketone bodies are used, thiophorase transfers coA from succinyl coA onto acetoacetate, making acetoacetyl coA

Question 27

The rate limiting enzyme in ketone biosynthesis is mitochondrial _______

The key enzyme in UTILIZATION of ketone bodies is ______, which transfers CoA from succinyl coA onto acetoacetate

Answer 27

The rate limiting enzyme in ketone biosynthesis is mitochondrial HMG-CoA Synthase (this is found only in the liver)

The key enzyme in the utilization of ketone bodies is Thiophorase, which transfers CoA from succinyl coA onto acetoacetate. Thiophorase is NOT found in the liver.

Question 28

Epi will ______ the mobilization of FA’s from TAG

Insulin will _____ the mobolization of FA’s from TAG

Answer 28

Epi will INCREASE the mobolization of FA’s from TAG

Insulin will inhibit it

Question 29

Citrate and Insulin _______ to FA synthesis via the enzyme acetyl-coA carboxylase

Glugacon and Epi _____ the beta-oxidation of fatty acids to form ketone bodies via the enzyme ___

Answer 29

Citrate and insulin increase FA synthesis via the enzyme acetyl coA carboxylase

Glucagon and Epi (need energy) will INCREASE the beta oxidation of fatty acids by activating CPT-1

Question 30

Glucagon and Epi will _____ fatty acid biosynthesis

Answer 30

Glucagon and Epi will inhibit synthesis of fatty acids because you NEED energy (want to break them down)

This is due through inhibition of acetyl coA carboxylase

Question 31

The only known inhibitor of CPT-1 is _____

Which is the product of ____

Therefore insulin indirectly ______

Answer 31

The only known inhibitor of CPT-1 is malonyl coA

Which is the product of the rate limiting enzyme in fatty acid biosynthesis (acetyl coA carboxylase)

Therefore, insulin (which promotes fatty acid biosynthesis) will indirectly inhibit (downstream) beta oxidation of fatty acids