Ch 22 - Oxidation Of Fatty Acids: Ketogenesis

Question 1

Each step in fatty acid oxidation involves _______________, is catalyzed by separate enzymes, utilizes ____ and _____ as coenzymes, and generates ATP.

Answer 1

Acyl-CoA derivatives

NAD+ and FAD

Question 2

It is an aerobic process, requiring the presence of oxygen.

Answer 2

Fatty acid oxidation

Question 3

_____________ is a characteristic of starvation and of diabetes mellitus and leads to increased ketone body production by the liver (ketosis).

Answer 3

Increased fatty oxidation

Question 4

Because gluconeogenesis is dependent upon fatty acid oxidation, any impairment in fatty acid oxidation leads to _________.

Answer 4

Hypoglycemia

Question 5

This occurs in various states of CARNITINE DEFICIENCY, or deficiency of essential enzymes in fatty acid oxidation, for example _______________ or inhibtion of fatty acid oxidation by poisons, for example ___________.

Answer 5

Carnitine palmitoyltransferase

Hypoglycin

Question 6

Oxidation of fatty acids occurs in ___________.

Answer 6

Mitochondria

Question 7

Fatty acids are transported in the blood as ______________.

Answer 7

Free fatty acids

Question 8

Free fatty acids (FFAs) also called __________ or _________ are fatty acids that are in the UNESTERIFIED STATE.

Answer 8

Unesterified (UFA) or nonesterified (NEFA) fatty acids

Question 9

In plasma, longer chain FFA are combined with _______ and in the cell they are attached to a FATTY ACID BINDING PROTEIN so that in fact they are never really “free”.

Answer 9

Albumin

Question 10

____________ are more WATER-SOLUBLE and exist as the UNIONIZED ACID or as a FATTY ACID ANION.

Answer 10

Shorter chain fatty acids

Question 11

Fatty acids are activated before being _________.

Answer 11

Catabolized

Question 12

True or False:

Fatty acids must be first converted to an active intermediate before they can be catabolized.

Answer 12

True

Question 13

This is the only step in the complete degradation of a fatty acid that requires energy from ATP.

Answer 13

Fatty acids are activated before being catabolized

Question 14

In the presence of ATP and coenzyme A, the enzyme ____________ catalyzes the conversion of a fatty acid to an “active fatty acid” or ____________ using one high-energy phosphate and forming AMP and PPi.

Answer 14

Acyl-coA synthetase (thiokinase)

Acyl-CoA

Question 15

The PPi is hydrolyzed by ___________ with the loss of a further high-energy phosphate ensuring that the overall reaction goes to completion

Answer 15

Inorganic pyrophosphatase

Question 16

Found in the endoplasmic reticulum, peroxisomes and inside and on the outer membrane of mitochondria

Answer 16

Acyl-CoA synthetases

Question 17

Long-chain fatty acids penetrate the inner mitochondrial membrane as _____________.

Answer 17

Carnitine derivatives

Question 18

Is widely distributed and is particularly abundant in muscle.

Answer 18

Carnitine (B-hydroxy-y-trimethylammonium butyrate)

Question 19

True or False: Long-chain acyl-CoA cannot penetrate the inner membrane of mitochondria.

Answer 19

True

Question 20

Located in the outer mitochondrial membrane, transfers long-chain acyl group from CoA to carnitine forming __________ and releasing CoA.

Answer 20

Carnitine palmitoyltransferase-I

Acylcarnitine

Question 21

Acylcarnitine is able to penetrate the inner membrane and gain access to the B-oxidation system of enzymes via the inner membrane exchange transporter _________________.

Answer 21

Carnitine-acylcarnitine translocase

Question 22

The acyl group is then transferred to CoA so that acyl-CoA is reformed and carnitine is liberated. This reaction is catalyzed by ____________ which is located on the inside of the inner membrane

Answer 22

Carnitine palmitoyltransferase II

Question 23

In the ____________, two carbons at a time are cleaved from acyl-CoA molecules starting at the CARBOXYL END.

Answer 23

B-oxidation pathway

Question 24

The two-carbon units formed are acetyl-CoA thus __________ forms eight acetyl-CoA molecules.

Answer 24

Palmitoyl-CoA

Question 25

The B-oxidation cycle generates ________ and _______.

Answer 25

FADH2 and NADH

Question 26

Several enzymes known collectively as __________ are found in the mitochondrial matrix or inner membrane adjacent to the respiratory chain.

Answer 26

Fatty acid oxidase

Question 27

In the process, large quantities of the reducing equivalents FADH2 and NADH are generated and are used to form ATP by _____________.

Answer 27

Oxidative phosphorylation

Question 28

The first step is the removal of TWO hydrogen atoms from the 2(a) and 3(b) carbon atoms, catalyzed by __________ and requiring ______. This results in the formation of 🔼2-trans-enoyl-CoA and FAD.

Answer 28

Acyl-CoA dehydrogenase FAD

Question 29

The reoxidation of FADH2 by the respiratory chain requires the meditation of another flavoprotein termed _____________.

Answer 29

Electron-transferring flavoprotein

Question 30

Water is added to saturate the double bond and form 3-hydroxy-acyl-CoA, catalyzed by _______________.

Answer 30

🔼2-enoyl-CoA hydratase

Question 31

The 3-hydroxy derivative undergoes further dehydrogenation on the 3-carbon cataylzed by _______________ to form the corresponding 3-ketoacyl-CoA compound. In this case, _____ is the coenzyme involved.

Answer 31

L (+) - 3-hydroxyacyl-CoA dehydrogenase NAD+

Question 32

Finally, 3-ketoacyl-CoA is split at the 2,3-position by _________ forming acetyl-CoA and a new acyl-CoA two carbons shorter than the original acyl-CoA molecule.

Answer 32

Thiolase (3-ketoacyl-CoA-thiolase)

Question 33

The shorter acyl-CoA formed in the cleavage reenters the oxidative pathway at __________.

Answer 33

Reaction 2

Question 34

For example, after SEVEN cycles the C16 fatty acid, _________ would be converted to eight acetyl CoA molecules.

Answer 34

Palmitate

Question 35

Since acetyl-CoA can be oxidized to CO2 and water via the ______________, the complete oxidation of fatty acids is achieved.

Answer 35

Citric acid cycle

Question 36

Oxidation of a fatty acid with an ODD NUMBER of carbon atoms yields ACETYL-CoA plus a molecule of ___________.

Answer 36

Propionyl-CoA

Question 37

Fatty acids with an odd number of carbon atoms are oxidized by the pathway of B-oxidation described above producing acetyl CoA until a three-carbon __________ residue remains.

Answer 37

Propionyl-CoA

Question 38

This compound is converted to __________, a consistuent of the citric acid cycle.

Answer 38

Succinyl-CoA

Question 39

Hence, the propionyl residue from an odd-chain fatty acid is the only part of a fatty acid that is _________.

Answer 39

Glucogenic

Question 40

Oxidation of fatty acids produces a large quantity of ______.

Answer 40

ATP

Question 41

Transport of electrons from FADH2 and NADH via the respiratory chain leads to the synthesis of ____ high-energy phosphates for each of the seven cycles needed for the breakdown of the C16 fatty acid, palmitate to acetyl-CoA. (7 x 4 = 28)

Answer 41

4

Question 42

A total of ___ mol of acetyl-CoA is formed and each gives rise to ___ mol of ATP on oxidation in the CTA making ___ mol.

Answer 42

8 10 80

Question 43

Two must be substracted for the initial activation of the fatty acid, yielding a net gain of ____ mol of ATP per mole of palmitate or 106 x 30.5 = 3233 kJ. This represents ___% of the free energy of combustion of palmitic acid.

Answer 43

106 mol 33%

Question 44

_______ oxidize very long chain fatty acids.

Answer 44

Peroxisomes

Question 45

A modified form of B-oxidation is found in _______ and leads to the formation of acetyl-CoA and H2O2 (from the flavoprotein-linked dehydrogenase step), which is broken down by ______.

Answer 45

Peroxisomes Catalase

Question 46

True or False: Thus, the dehydrogenation in peroxisomes is not linked directly to phosphorylation and the generation of ATP.

Answer 46

True

Question 47

The system facilitates the oxidation of VERY LONG CHAIN FATTY ACIDS. The enzymes responsible are induced by high-fat diets and in some species by hypolipidemic drugs such as _________.

Answer 47

Clofibrate

Question 48

The enzymes in peroxisomes do not attack shorter chain fatty acids; the B-oxidation sequence ends at __________.

Answer 48

Octanoyl-CoA

Question 49

Octanoyl and acetyl groups are both further oxidized in ____________.

Answer 49

Mitochondria

Question 50

Another role of peroxisomal B-oxidation is to _______ the side chain of cholesterol in bile acid formation.

Answer 50

Shorten

Question 51

__________ also take part in the synthesis of ETHER GYLCEROLIPIDS, CHOLESTEROL and DOLICHOL.

Answer 51

Peroxisomes

Question 52

Oxidatiom of unsaturated fatty acids occurs by a _______________.

Answer 52

Modified B-oxidation pathway

Question 53

The CoA esters of unsaturated fatty acids are degraded by the enzymes normally responsible for B-oxidation until either a ______________ compound or a _____________ compound is formed, depending upon the position of the double bonds.

Answer 53

🔼3-cis-acyl-CoA or 🔼4-cis-acyl-CoA compound

Question 54

The former compound is isomerized _________________ to the corresponding 🔼2-trans-CoA stage of B-oxidation for subsequent hydration and oxidation.

Answer 54

🔼3cis -> 🔼2-trans-enoyl-CoA isomerase

Question 55

____________ occurs when there is a high rate of fatty-acid oxidation in the liver.

Answer 55

Ketogenesis

Question 56

Under merabolic conditions associated with a high rate of fatty acid oxidation, the liver produces considerable quantities of _______ and _________.

Answer 56

Acetoacetate and D(--)-3-hydroxybutyrate (B-hydroxybutyrate)

Question 57

Acetoacetate continually undergoes spontaneous decarboxylation to yield ____________.

Answer 57

Acetone

Question 58

Acetoacetate and 3-hydroxybutyrate are interconverted by the mitochondrial enzyme ________________; the equilibrium is controlled by the mitochondrial [NAD+]/[NADH] ratio, that is the ____________.

Answer 58

D(-)-3-hydroxybutyrate dehydrogenase

Question 59

The concentration of total ketone bodies in the blood of well-fed mammals does not normally exceed ____ mmol/L except in ruminants, where 3-hydroxybutyrate is formed continously from _________ (a product of ruminal fermentation) in the rumen wall.

Answer 59

0.2 mmol/L Butyric acid

Question 60

In vivo, _____ appears to be the only organ in nonruminants to add significant quantities of ketone bodies to th blood.

Answer 60

Liver

Question 61

Extrahepatic tissues utilize acetoacetate and B-hydroxybutyrate as ______________.

Answer 61

Respiratory substrates

Question 62

________ is a waste product which, as it is VOLATILE, can be excreted via the lungs.

Answer 62

Acetone

Question 63

True or False: Because there is active synthesis but LITTLE UTILIZATION of ketone bodies in the liver, while they are used but not produced in extrahepatic tissues, there is a net flow of the compounds to the extrahepatic tissues.

Answer 63

True

Question 64

________________ is an intermediate in the pathway of ketogenesis.

Answer 64

3-hydroxy-3-methylglutaryl-CoA (HMG-CoA)

Question 65

Enzymes responsible for ketone body formation are associated mainly with the _________.

Answer 65

Mitochondria

Question 66

The term ketones should not be used as there are ketones in blood that are not ketone bodies, for example, __________ and _________.

Answer 66

Pyruvate and fructose

Question 67

Two acetyl-CoA molecules formed in B-oxidation condense to form acetoacetyl-CoA by a reversal of the __________ reaction.

Answer 67

Thiolase

Question 68

___________, which is a starting material for ketogenesis, also arises directly from the terminal FOUR carbons of a fatty acid during B-oxidation.

Answer 68

Acetoacetyl-CoA

Question 69

Condensatiom of acetoacetyl-CoA with another molecule of acetyl-CoA by _________________ forms 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA).

Answer 69

3-hydroxy-3-methylglutaryl-CoA synthase

Question 70

______________ then causes acetyl-CoA to split off from the HMG-CoA, leaving free aceto-acetate.

Answer 70

3-hydroxy-3-methylglutaryl-CoA lyase

Question 71

True or False: BOTH ENZYMES must be present in mitochondria for ketogenesis to take place.

Answer 71

True

Question 72

____________ is quantitatively the predominant ketone body present in the blood and urine in ketosis

Answer 72

D(-)-3-hydroxybutyrate

Question 73

Serve as a fuel for extrahepatic tissues.

Answer 73

Ketone bodies

Question 74

Acetoacetat once formed cannot be reactivated directly except in the _________, where it is used in a much less active pathwat as a precursor in cholesterol synthesis.

Answer 74

Cytosol

Question 75

In extrahepatic tissues, acetoacetate is activated to acetoacetyl-CoA by ___________________.

Answer 75

Succinyl-CoA-acetoacetate CoA transferase

Question 76

With the addition of CoA, the acetoacetyl-CoA is split into two acetyl-CoAs by _________ and oxidized in the citric acid cycle.

Answer 76

Thiolase

Question 77

If the blood level is raised, oxidation of ketone bodies increases until, at a concentration of ~____ mmol/L, the oxidative machinery is saturated.

Answer 77

12 mmol/L

Question 78

Is due to increased production of ketone bodies by the liver rather than to a deficiency in their utilization by extrahepatic tissues.

Answer 78

Ketonemia

Question 79

Is difficult to oxidixe IN VIVO and to a large extent is volatilized in the lungs.

Answer 79

Acetone

Question 80

In ____________, the loss of ketone bodies via the urine is only a few percent of the total ketone body production and utilization.

Answer 80

Moderate ketonemia

Question 81

Measurement of the ________, not the ketonuria, is the preferred method of assesing the severity of ketosis.

Answer 81

Ketonemia

Question 82

Ketosis does not occur in vivo unless there is an increase in the level of circulating ______ that arise from lipolysis of triacylglycerol in adipose tissue.

Answer 82

FFAs

Question 83

Are the precursors of ketone bosies in the liver.

Answer 83

FFAs

Question 84

The liver, both in fed and in fasting conditions, extracts ~__% of the FFAs passing through it, so that a high concentrations the flux passing into the liver is substantial.

Answer 84

30%

Question 85

Therefore, the factors regulating ______________ from adipose tissue are important in controlling ketogenesis.

Answer 85

Mobilization of FFA

Question 86

After uptake by the liver, FFAs are either _________ to CO2 or ketone bodies or ___________ to triacylglycerol and phospholipid.

Answer 86

B-oxidized Esterified

Question 87

There is regulation of entry of fatty acids into th oxidative pathway by _______________ and the remainder of the fatty acid taken up is eterified.

Answer 87

Carnitine palmitoyltransferase-I (CPT-I)

Question 88

CPT-I activity is ____ in the fed state, leading to depression of fatty acid oxidation and ____ in starvation, allowing fatty acid oxidation to increase.

Answer 88

Low High

Question 89

____________ the initial intermediate in fatty acid biosynthesis formed by acetyl-CoA carboxylase in the fed state, is a potent inhibitor of CPT-I.

Answer 89

Malonyl-CoA

Question 90

FFA enter the liver cell in low concentrations and are nearly all esterified to acylglycerols and transported out of the liver in _______.

Answer 90

VLDL

Question 91

These events are reinforced in starvation by a decrease in ____________.

Answer 91

Insulin/glucagon ratio

Question 92

Impaired oxidation of fatty acids gives rise to disease often associated with _____________.

Answer 92

Hypoglycemia

Question 93

A fall in the concentration of _____________, particularly within the mitochondria, can impair the ability of the citric acid cycle to metabolize acetyl-CoA and divert fatty acid oxidation toward ketogenesis.

Answer 93

oxaloacetate

Question 94

_______________ can occur particularly in the newborn— and especially in preterm infants—owing to inadequate biosynthesis or renal leakage.

Answer 94

Carnitine deficiency

Question 95

Symptoms of deficiency include __________, which is a consequence of impaired fatty acid oxidation and lipid accumulation with muscular weakness.

Answer 95

hypoglycemia

Question 96

______________ affects only the liver, resulting in reduced fatty acid oxidation and ketogenesis, with hypoglycemia.

Answer 96

Inherited CPT-I deficiency

Question 97

_________________ affects primarily skeletal muscle and, when severe, the liver

Answer 97

CPT-II deficiency

Question 98

The sulfonylurea drugs (_____________________), used in the treatment of type 2 diabetes mellitus, reduce fatty acid oxidation and, therefore, hyperglycemia by inhibiting CPT-I.

Answer 98

glyburide [glibenclamide] and tolbutamide

Question 99

Inherited defects in the enzymes of β-oxidation and ketogenesis also lead to _____________, _______________ and _____________.

Answer 99

nonketotic hypoglycemia, coma, and fatty liver.

Question 100

Defects are known in long-and short-chain 3-hydroxyacyl-CoA dehydrogenase (deficiency of the long-chain enzyme may be a cause of __________________).

Answer 100

acute fatty liver of pregnancy

Question 101

3-KetoacylCoA thiolase and HMG-CoA lyase deficiency also affect the degradation of ___________, a ketogenic amino acid.

Answer 101

leucine

Question 102

Jamaican vomiting sickness is caused by eating the unripe fruit of the akee tree, which contains the toxin _____________.

Answer 102

hypoglycin

Question 103

This inactivates medium- and short-chain acyl-CoA dehydrogenase, inhibiting β-oxidation and causing hypoglycemia.

Answer 103

Jamaican vomitting disease

Question 104

________________ is characterized by the excretion of C6´C10 ω-dicarboxylic acids and by nonketotic hypoglycemia, and is caused by a lack of mitochondrial medium-chain acyl-CoA dehydrogenase.

Answer 104

Dicarboxylic aciduria

Question 105

______________ is a rare neurologic disorder due to a metabolic defect that results in the accumulation of phytanic acid, which is found in dairy products and ruminant fat and meat.

Answer 105

Refsum disease

Question 106

___________ is thought to have pathological effects on membrane function, protein prenylation, and gene expression.

Answer 106

Phytanic acid

Question 107

__________________ occurs in individuals with a rare inherited absence of peroxisomes in all tissues. They accumulate C26´C38 polyenoic acids in brain tissue and also exhibit a generalized loss of peroxisomal functions. The disease causes severe neurological symptoms, and most patients die in the first year of life.

Answer 107

Zellweger (cerebrohepatorenal) syndrome

Question 108

The basic form of ketosis occurs in ___________ and involves depletion of available carbohydrate coupled with mobilization of FFA.

Answer 108

starvation

Question 109

_________________ of ketosis are found under conditions of high-fat feeding and after severe exercise in the postabsorptive state.

Answer 109

Nonpathologic forms

Question 110

Acetoacetic and 3-hydroxybutyric acids are both _____________ and are buffered when present in blood or other tissues.

Answer 110

moderately strong acids