FA Oxidation and Ketone Bodies

Question 1

FA oxidation occurs where?

Answer 1

in mitochondria

Question 2

True or false? Long-chain FAs can’t enter the mitochondria without transport mechanisms. Medium and short-chain FAs can enter by diffusion.

Answer 2

true

Question 3

Medium-chain and short-chain FAs are more water soluble. They are not incorporated into ____. They enter the portal blood and are transported primarily to the ____ where they enter by _____.

Answer 3

chylomicrons; liver; diffusion

Question 4

In the mitochondria, medium and short-chain FAs are activated to ___-___ for beta-oxidation

Answer 4

acyl-CoAs

Question 5

FA binding proteins in the plasma membrane aid in the transport of long-chain FAs from ___ in the blood

Answer 5

albumin

Question 6

Long-chain FAs enter the mitochondria as fatty _____

Answer 6

acylcarnitines

Question 7

A fatty acyl-CoA synthase on the ___ mitochondrial membrane produces acyl-CoAs which enter the mitochondrial ____-membrane space

Answer 7

outer; inter

note: CPT I catalyzes this reaction

Question 8

_____ are transported across the mitochondrial inner membrane in exchange for “free” _____ by cranitittine:acylcarnitine translocase

Answer 8

acylcarnitines; carnitine

Question 9

Inside the mitochondria, the acyl-CoA is “____” by CPT II

Answer 9

“regenerated”

Question 10

Beta-oxidation of long-chain acyl-CoAs is a series of 4 reactions repeated cyclically. Each cycle produces how many acetyl-Coa, FADH2, NADH, and acyl-CoA

Answer 10

acetyl-CoA: 1
FADH2: 1
NADH: 1
acyl-CoA: one reduced in length by 2 carbons

Question 11

Since the 4 reactions of beta-oxidation occur inside the mitochondria, the reduced cofactors are substrates for ____ ____, and the acetyl-CoA is a substrate for the ____ ____

Answer 11

oxidative phosphorylation; TCA cycle

Question 12

Each of the 4 reactions in beta-oxidation is catalyzed by a number of enzymes which have various specificities for chain length. For the following acyl-CoA dehydrogenase, give the light of chain it prefers.
VLCAD
LCAD
MCAD
SCAD

Answer 12

VLCAD: prefers C12 to C24
LCAD: C12 to C16
MCAD: C6 and C8
SCAD: C4>C6>C8

Question 13

The major control of beta-oxidation is exerted at which enzyme?

Answer 13

CPT I

Question 14

CPT I is inhibited by ____-___

Answer 14

malonyl-CoA

Question 15

Malonyl-CoA is the produce of ___-___ carboxylase and is the substrate for FA ____

Answer 15

acetyl-CoA; synthesis

Question 16

Acetyl-CoA carboxylase is stimulated (malonyl-CoA is produced) in what situation?

Answer 16

when insulin predominates

Question 17

Acetyl-CoA carboxylase is inhibitied (malonyl-CoA concentration decreases) in what situation?

Answer 17

when glucagon predominates

Question 18

How do odd-numbered FAs go through Beta-oxidation?

Answer 18

1. at the final stage, one molecule of acetyl-CoA and one molecule of propionyl-CoA are produced
2. propionyl-CoA is converted to succinyl-CoA

Question 19

____-___ is a gluconeogenic precursor, and thus the only part of a FA which can result in the net synthesis of glucose

Answer 19

Succinyl-CoA

Question 20

Oxidation of unsaturated FAs have to be handled differently because the double bonds are in the ____ configuration and may involve an ___-numbered carbon

Answer 20

cis; odd

Question 21

Unsaturated FAs are oxidized with help from two enzymes. What are they?

Answer 21

1. enoyl-CoA isomerase

2. 2,4-dienoyl-CoA reductase

Question 22

Where does oxidation of very long chain FAs (C24-C26) occur?

Answer 22

peroxisomes

note: called “modified” beta-oxidation

Question 23

What are the products of very long chain FA “modified” beta oxidation?

Answer 23

acetyl-CoA and a fatty acyl-CoA reduced by 2 carbons

Question 24

The acyl-CoA oxidation in modified beta oxidation is not linked to cofactor ____

Answer 24

reduction; means no energy is provided by this step

Question 25

The peroxisomal oxidation (modified beta oxidation) proceeds until the acyl-CoA is about ___ carbons long

Answer 25

8

Question 26

The octanoyl-CoA and the acetyl-CoA produced by peroxisomal oxidation are transported to the ____ for further oxidation

Answer 26

mitochondria

Question 27

True or false? animals do not produce branched-chain fatty acids

Answer 27

true

Question 28

The most common long-chain branched FA is a degradation product of ____

Answer 28

chlorophyll

Question 29

long-chain branched FAs are oxidized where?

Answer 29

peroxisomes

Question 30

What are the products of long-chain branched FA oxidation?

Answer 30

1. CO2 2. propionyl-CoA 3. acetyl-CoA

Question 31

In regards to w-oxidation of FAs, the w-carbon is the terminal ___ group of the FA

Answer 31

methyl

Question 32

w-oxidation occurs where? requires what?

Answer 32

occurs in ER | requires cytochrome P450, O2, and NADPH

Question 33

The w-CH3 group is oxidized first to an ____ and then to a ____ ___

Answer 33

alcohol; carboxylic acid note: produces a dicarboxylic acid

Question 34

The w-oxidation pathway is though to function to produce more water-soluble compounds from water insoluble FAs. The products may be oxidized as ___-chain FAs or they can be ___

Answer 34

medium; excreted

Question 35

Ketone bodies are formed from ___-___ from FA oxidation

Answer 35

acetyl-CoA

Question 36

Name the 3 ketone bodies

Answer 36

acetoacetate, beta-hydroxybutyrate; acetone

Question 37

The ketone bodies are synthesized in ____ ____

Answer 37

liver mitochondria

Question 38

___-___ is an intermediate in the ketone body pathway

Answer 38

HMG-CoA

Question 39

The liver mitochondrial HMG-CoA synthase is an isozyme restricted to the mitochondria and functions only in what?

Answer 39

synthesis of ketone bodies

Question 40

The cytosolic HMG-CoA synthase of many cells is the isozyme of ____ synthesis

Answer 40

cholesterol

Question 41

Ketone bodies are utilized by peripheral tissues for energy - primarily the ___ and ____

Answer 41

muscle and brain note: the enzymes are mitochondrial

Question 42

The ___ only produces ketone bodies, and the ___ ___ only utilizes ketone bodies

Answer 42

liver; peripheral tissue

Question 43

Only liver mitochondria contain the enzymes specific for the synthesis of ketone bodies. What are they?

Answer 43

1. mitochondrial HMG-CoA synthase | 2. HMG-CoA lyase

Question 44

Peripheral tissues (muscle and brain) express the enzyme specific for utilization of ketone bodies. What is it?

Answer 44

acetoacetate: succinyl-CoA transferase

Question 45

True or false? ketone bodies are formed in the liver only when the liver is supplied with high concentrations of FAs

Answer 45

true

Question 46

Where do the FAs used to synthesize ketone bodies come from?

Answer 46

lipolysis of adipose tissue

Question 47

In what individuals is ketone body production usually seen?

Answer 47

starving or uncontrolled type 1 diabetes

Question 48

After an over night fast, the concentration of ketone bodies in the blood is on the order of ____ mM. After a 2 day fast? After 40 days of starvation?

Answer 48

overnight: 0.05 2 days: 2mM 40 days: 7mM

Question 49

____ is derived from the spontaneous, non-enzymatic decarboxylation of acetoacetate

Answer 49

acetone

Question 50

The amount of FAs provided to the liver is under the control of ____ and ____

Answer 50

insulin and glucagon

Question 51

This is the most common genetic disease of lipid metabolism (1/15000). It is associated with non-ketotic hypoglycemia upon fasting, fatty infiltration of liver, and short chain dicarboxylic acids in urine

Answer 51

MCAD (medium-chain acyl-CoA dehydrogenase) deficiency

Question 52

In regards to MACD, non-ketotic hypoglycemia upon fasting may be deadly in an overnight fast of which individuals?

Answer 52

children

Question 53

In regards to MACD, Fatty acids which cannot be oxidized are assembled into ____ which exceed the ability of the liver to secrete as ___

Answer 53

TAG; VLDL

Question 54

In regards to MACD, the short chain dicarboxylic acids in the urine arise from where?

Answer 54

w-ocidation of medium and short chain fAs which can't be oxidized by beta-oxidation

Question 55

What is the treatment of MACD?

Answer 55

avoid fasting

Question 56

In this disorder of lipid oxidation, insufficient FAs are delivered into the mitochondria. Symptoms include non-ketotic hypoglycemia due to decreased energy for gluconeogenesis

Answer 56

carnitine deficiency

Question 57

In this disorder of lipid oxidation, symptoms include non-ketotic hypoglycemia due to decreased beta-oxidation, hepatomegaly with fatty infiltration, increased plasma carnitine. It can be overcome by medium-chain FAs

Answer 57

CPT I deficiency

Question 58

This disorder of lipid oxidation can be described by a rare genetic deficiency of a component required for peroxisomal oxidation of branched-chain FAs. Its associated with serious neurological issues.

Answer 58

Refsum disease

Question 59

How is Refsum disease treated?

Answer 59

by reducing phytanic acid from diet (restrict dairy and meat)

Question 60

This disorder of lipid oxidation is due to eating the unripe fruit of the akee tree, which contains hypoglycin - It is a potent inhibitor of acyl-CoA dehydrogenase. Symptoms are non-ketotic hypoglycemia

Answer 60

Jamaican vomitting sickness note: one case reported a blood glucose concentration of 3 mg/dl