Fatty Acid Oxidation

Question 1

What are the two most common disorders of fatty acid oxidation?

Answer 1

Carnitine deficiency and MCAD deficiency

Question 2

True or false: all fatty acids need to be acylated (by fatty acyl co-a synthetase) to get into mitochondrial intermembrane space.

Answer 2

False. Only long-chain fatty acids do; short- and medium-chain fatty acids can diffuse across the mitochondrial membrane.

Question 3

What inhibits carnitine acetyltransferase 1 and carnitine palmitoyltransferase 1?

Answer 3

Malonyl co-a. Think about it: malonyl co-a is a product in the synthesis of fatty acids, so it makes sense that something that signals fatty acid synthesis should inhibit the fatty acid breakdown pathway (otherwise it would be a futile cycle).

Question 4

In the mitochondria, fatty acids can _____________.

Answer 4

be broken down via beta oxidation to produce acetyl co-a that generates NADH, FADH2, and GTP

Question 5

Very long chain fatty acids must first be _________________ before going into the mitochondria.

Answer 5

degraded in peroxisomes

Question 6

Hormone-sensitive lipase is active when ____________.

Answer 6

phosphorylated (because glucagon and epinephrine activate adenylyl cyclase and activate the protein kinase that phosphorylates hormone-sensitive lipase)

Question 7

Acetyl co-a carboxylase is inhibited when ___________ (a covalent modification).

Answer 7

phosphorylated by the effects of epinephrine and glucagon binding; insulin activates a phosphatase that breaks the phosphate group off and activates this enzyme

Question 8

Carnitine acetyltransferase binds acetyl groups to fatty acids, which can then ______________.

Answer 8

pass through the inner mitochondrial membrane (carnitine acetyltransferase is in the outer mitochondrial membrane)

Question 9

Carnitine deficiency leads to massive accumulation of ________________.

Answer 9

fat within the cytosol of hepatocytes

Question 10

Trace the beta oxidation pathway.

Answer 10

Cis acyl co-a (in mitochondria)
(Acyl co-a dehydrogenase) –generates a trans double bond
Trans acyl co-a
(Enoyl co-a hydratase) – adds H2O across the double bond
3-Hydroxyacyl co-a
(Beta-hydroxy-co-a-dehydrogenase) – oxidizes OH to O=
3-Ketoacyl-co-a
(Thiolase) – breaks off oxidized group
Acetyl co-a

Question 11

One molecule of palmitoyl acid can produce _________.

Answer 11

131 molecules of ATP

Question 12

Odd-numbered chains require ____________.

Answer 12

an extra step that adds a carboxyl group to the three-carbon remainder that ultimately gets put into the TCA cycle at succinyl co-a

Question 13

Describe Zellweger syndrome.

Answer 13

deficiency in peroxisomal beta-oxidation enzymes, similar to X-linked adenoleukodystrophy

Question 14

______________ is characterized by increased urinary excretion of carnitine esters, hypoglycemia, low levels of ketones during fasting state, and sleepiness.

Answer 14

Acyl co-a dehydrogenase deficiency (the most common disorder of beta-oxidation)

Question 15

Beta-oxidation is regulated at the level of _______________.

Answer 15

carnitine acyltransferase

Question 16

Ketone bodies are produced in the __________ in the presence of excess _____________.

Answer 16

liver; acetyl co-a

Question 17

What happens to ketone bodies?

Answer 17

The liver does not have the enzyme to reconvert beta-hydroxybutyrate to acetyl-co-a, but the brain and muscles do. As such, ketones diffuse out to the peripheral tissues and are reconverted to acetyl co-a.

Question 18

Why do those with T1DM produce ketones?

Answer 18

Lack of insulin leads to activation of hormone-sensitive lipase which creates more fatty acids. The excess fatty acids undergo beta-oxidation and produce excess acetyl co-a, which then leads to ketone conversion.

Question 19

Qualitatively, what are the four steps of beta-oxidation?

Answer 19

Dehydrogenation
Hydration
Dehydrogenation
Cleavage

Question 20

More than ________ percent of fatty acids in the body are stored as triglycerides.

Answer 20

90

Question 21

Carnitine palmitoyl transferase is inhibited by ______________.

Answer 21

malonyl co-a (a signal of fatty acid synthesis)

Question 22

What is produced by the four-step beta oxidation pathway?

Answer 22

1 FADH2
1 NADH
1 Acetyl co-a

Question 23

Medium-chain fatty acyl dehydrogenase deficiency has been associated with ___________.

Answer 23

SIDS

Question 24

Describe the process of ketogenesis.

Answer 24

During fatty acid oxidation, the elevated acetyl co-a and NADH lead to inhibition of pyruvate dehydrogenase and activate pyruvate carboxylase (producing oxaloacetate for gluconeogenesis). Additionally, the excess acetyl co-a favors ketone synthesis.

Question 25

Trace the ketone synthesis pathway.

Answer 25

Acetyl co-a
(Thiolase)
Acetoacyl co-a
(HMG synthase) 
HMG co-a
(HMG co-a lyase) 
Acetoacetate
(3-hydroxybutyrate dehydrogenase) –produces NADH

Question 26

Ketones are the primary fuel source in ____________.

Answer 26

the cardiac muscle and renal cortex

Question 27

In order to use ketones, tissues must have ___________ to initiate conversion of 3-hydroxybutyrate to acteyl co-a.

Answer 27

thiophorase

Question 28

The primary regulated step in fatty acid oxidation is ______________, while ___________ is the rate-limiting step.

Answer 28

hormone-sensitive lipase; CAT-1

Question 29

Propionyl co-a will be found in ___________.

Answer 29

oxidation of odd-numbered fatty acids