Metabolism 7

Question 1

Define acylglycerol.

Answer 1

Compounds in which one or more of the three OH groups of glycerol is
esterified.

Question 2

Describe triacylglycerols.

Properties of TAGs are determined by the fatty acids that they contain: Describe oils and fats.

Hydrophilic/Hydrophobic/ampipathic?

Do they form micelles?

Answer 2

-All three OH groups are esterified to fatty acids.
-At least two of the three substituent groups are usually different.
Asymmetric – R and R’’ are not equivalent.

-Properties of TAGs are determined by the fatty acids that they contain.
Oils - liquid at RT.
Fats- solid at RT.

Triacylglycerols are hydrophobic and do not form stable micelles.

Question 3

Define lipases.

How much of dietary fat and energy do they account for?

How much of TAG-FA is oleic acid? How much is unsaturated?

Answer 3

Lipases – enzymes that hydrolyze TAGs to glycerol and three fatty acids.

• Account for 90-95% dietary fat.
• Glycerol becomes Glucose
• Fatty acids account for 95% of biologically available energy.
• Dietary TAG consumption should be less that 30% of total calories.
• 46% of TAG-FA is oleic acid (18:1)
• 50% of TAG-FA is unsaturated.

Question 4

Describe Diacylglycerols and Monoacylglycerols.

Answer 4

also exist in small amounts as metabolic

intermediates.

Question 5

What is the rate limiting enzyme in lipid metabolism?

Answer 5

acetyl CoA carboxylase

Slide 4

Question 6

What happens in the lipid metabolism cycle when there is a need for ATP?

Answer 6

When there is a need for (ATP), fatty acids are mobilized from adipose tissue
triacylglycerols by the action of hormone-sensitive triacylglycerol lipase (HSTL).

Question 7

Describe Hormone-sensitive triacylglycerol lipase (HSTL/HSL)

What effect will epinephrine have?
Adrenocorticotropic hormone (ACTH)?
Insulin
Prostaglandins?
Thyroid hormones and adrenal cortical hormones?

Answer 7

Epinephrine is a major activator of HSTL via protein kinase A (PKA)-mediated
phosphorylation, which is cAMP-dependent.

Adrenocorticotropic hormone (ACTH) is also an activator of HSTL.
Insulin inhibits HTSL activity by dephosphorylation (and is therefore
antilipolytic).

Prostaglandins (PGE) is also antilipolytic.

Thyroid hormones & adrenal cortical hormones are permissive.

Although they do not activate the enzyme, their presence is required for normal
activity

Question 8

Draw a diagram of Synthesis and Degradation of Triacylglycerols by Adipose Tissue.

(Start with glucose from the liver and VLDL-TAG from the liver then outline their pathways).

What effect will insulin/epinephrine have?

Answer 8

(Slides # 8 and 9)

p 6

Question 9

Describe the role of perilipin.

What activates it? What does it do? What process is dependent upon its activity?

Answer 9

coats the surface of fat droplets and must be phosphorylated by PKA in order for HSTL to translocate to the surface of the fat droplet.

Question 10

Describe the fates of the products of TAG breakdown. Where do released fatty acids go?

Answer 10

1. Enter the circulation.
2. Bind to albumin.
3. Are carried to muscle, liver, etc.
4. For beta-oxidation and energy production.

Question 11

Describe the fates of the products of TAG breakdown. Where do released glycerol go?

Answer 11

1. Is transported to liver and kidney.
2. Glycerol kinase phosphorylates glycerol to glycerol 3-phosphate, which can be used in gluconeogenesis.

Slide 12, p 7

Question 12

Mobilization of fatty acids from adipose tissue triacylglycerols leads to increased circulating levels of fatty acids. These processes influence the activity of fatty acid oxidation, ketone body formation, fatty acid biosynthesis, glycolysis (muscle), and
gluconeogenesis (liver).

Describe how.
(Effect of epinephrine)

Answer 12

fatty acid oxidation- increase

ketone body formation- increase

fatty acid biosynthesis- decreased

glycolysis (muscle) -inhibits

gluconeogensis (liver) - increase

p 8

Question 13

What is the effect of fatty acyl CoA on acetyl CoA carboxylase?

Answer 13

Fatty acyl CoA’s (e.g. palmitoyl-CoA) allosterically inhibit acetyl-CoA
carboxylase, the rate-limiting enzyme in fatty acid biosynthesis.

Question 14

How does a rise in fatty acids affect beta oxidation?

How do fatty acids affect the production of malonyl-CoA? Explain. (Hint: What reaction does malonyl CoA play an important role in?)

Answer 14

A rise in fatty acids provides increased substrates for beta-oxidation of fatty
acids.

In addition, since fatty acids inhibit fatty acid biosynthesis (a), they inhibit the
production of malonyl-CoA, the only physiological inhibitor of carnitine palmitoyl
transferase-1 (the rate-limiting enzyme of beta-oxidation). A reduction of malonyl-CoA
increases fatty acid oxidation.

Question 15

How will increased beta oxidation of fatty acids affect the production of ketone bodies?

Answer 15

Increased beta-oxidation of fatty acids leads to increased formation of ketone bodies
in the liver.

Question 16

How will ATP change in tissues that metabolize fatty acids? What effect will this have on glycolysis and why?

Answer 16

In tissues that metabolize fatty acids, ATP will increase, and the increased ATP
production will inhibit glycolysis by inhibiting PFK-1.

The increased ATP production (c) can be used in part for gluconeogenesis.

Question 17

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

Answer 17

Mitochondrial fatty acid metabolism is the major energy-producing
(ATP-producing) pathway in the body.

Mitochondrial fatty acid metabolism generates considerable
(ATP). The ATP is formed as a result of the metabolism of NADH,
FADH

Mitochondrial beta-Oxidation of fatty acids is the major enrgy-producing (ATPproducing)
pathway in the body.

Question 18

Mitochondrial fatty acid metabolism is the major energy-producing
(ATP-producing) pathway in the body.

What are good users of fatty acids?

Answer 18

liver
kidney cortex
heart
skeletal muscle

slide 16

Question 19

Name some tissues that do not or cannot use fatty acids as an energy source.

Answer 19

Red blood cells
Brain
Nervous System
Adrenal Medulla
Lens

slide 7

Question 20

What is the equation and stoichiometry for the beta oxidation of fatty acids? (Use palmitate as an example).

How many ATP does the complete oxidaiton of palmitate yield?

Answer 20

Palmitoyl-CoA + 7 FAD + 7 NAD+ + 7 CoA + 7 H2O —–>
8 Acetyl-CoA + 7 FADH2 + 7 NADH + 7 H+

The complete oxidation of palmitate yields 106 ATP.

Question 21

What 3 things does each cycle of B oxidation generate?

How are fatty acids degraded?

Answer 21

1 Acetyl-CoA
1 NADH
1 FADH2

Fatty acids are degraded by the sequential removal of two-carbon units.
In each cycle, FADH2, NADH and Acetyl-CoA are produced. FADH2 & NADH are reoxidized by the electron transport chain; this process is accompanied by the production of ATP. The acetyl-CoA can be metabolized by the citric acid cycle; additional ATP is
produced in this process.

Question 22

What does carnitine do?

What happens if it is inhibited?

Answer 22

Carnitine transports long chain fatty acids into the mitochondrial matrix so they
can be degraded by beta-oxidation. Inhibition of fatty acid transport inhibits fatty acid oxidation, and decreases production of ATP.

p 11, slide 21/22

Question 23

Regulation of Carnitine Palmityoltransferase-I:

What is the only known inhibitor of this enzyme?

What leads to inhibition of CPT-1? Conversely, what may activate it?

Answer 23

The only known Inhibitor of
carnitine palmitoyltransferase is malonyl-CoA, the product of the rate-limiting enzyme
in fatty acid biosynthesis, acetyl-CoA carboxylase.

Factors that favor the activation of acetyl-CoA carboxylase and the production of malonyl-CoA lead to the inhibition of
CPT-I and beta-oxidation of fatty acids.

Factors that inhibit acetyl-CoA carboxylase lead to reduced levels of the CPT-I inhibitor (malonyl-CoA); hence CPT-I and fatty acid
oxidation will be activated.

Question 24

What is the difference between primary and secondary carnitine deficiency disorders?

Answer 24

Primary (defect in carnitine transporter);

secondary (defect in CPT-II or CPT-I).

Question 25

There are separate acylCoA
dehydrogenases for long,
medium, and short chain
fatty acids (LCAD, MCAD,
SCAD).

What can MCAD deficiency sometimes account for?

Answer 25

MCAD deficiency accounts
for some cases described as
“Reye-like” syndrome or
“sudden infant death
syndrome.”

p 12

Question 26

Describe the pathway of fatty acid B oxidation.

Answer 26

p 12, slide 25

Question 27

Where and when are ketone bodies formed?

Show/draw a flow chart.

Answer 27

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

1) TAC to free fatty acids -lipolysis in adipose tissue
2) blood (free fatty acids)
3) liver (Acyl-CoA beta oxidized to Acetyl CoA which through keogenesis ketone bodies are made… Acyl-CoA can also undergo esterification to acylglycerols and acetyl-CoA can undergo CAC, CO2 produced)

p 13

Question 28

Draw the pathway for formation of ketone body biosynthesis.

Where does this take place? What is rate limiting enzyme?

Answer 28

p 14

Ketone Biosynthesis: The rate-limiting enzyme in ketone biosynthesis is the
mitochondrial enzyme, HMG-CoA synthase. It is found only in liver.

Question 29

What is the key enzyme in ketone body utilization?

Show pathway.

Answer 29

Ketone Utilization: The key enzyme in ketone body utilization is the
acetoacetate:succinyl-CoA CoA transferase enzyme which transfers CoA from
succinyl CoA to acetoacetate. This enzyme is not found in liver.

slide 28, p 14

Question 30

Ketone bodies are formed in the liver; they are used by other tissues for energy production. Show how used in liver, blood, and extrahepatic tissues.

Answer 30

p 15

Question 31

The Regulation of Ketone Body Formation Is Related to the
Regulation of Fatty Acid Mobilization and Beta-Oxidation.

Show how through flow chart.

Answer 31

Slide 33-35

p 16