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M1 > Fatty Acid Catabolism > Flashcards

Fatty Acid Catabolism Flashcards

1
Q

cells can obtain fatty acid fuels from four sources:

A
  1. fats consumed in the diet fats
  2. stored in cells as lipid droplets
  3. fats synthesized in one organ for export to another
  4. fats obtained by autophagy
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2
Q

Dietary Fats Are Absorbed in the Small Intestine

A
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3
Q

apolipoproteins

targets:

A

proteins in their lipid-free form that bind lipids to form lipoproteins

target triacylglycerols, phospholipids, cholesterol, and cholesteryl esters for transport between organs

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4
Q

chylomicrons

A

particles consisting of triacylglycerols, cholesterol, and apolipoproteins

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5
Q

Storage of Excess Fatty Acids

A
  • fatty acids are converted to triacylglycerols in the liver
  • triacylglycerols are packaged with specific apolipoproteins into VLDLs
  • VLDLs are secreted and transported in the blood to adipose tissue
  • triacylglycerols are removed and stored in lipid droplets within adipocytes in the adipose tissue
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6
Q

Hormones trigger mobilization of

A

stored triacylglycerols

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7
Q

lipid droplets

A

organelles stored in adipocytes and steroid-synthesizing cells that contain neutral lipids

contain a core of triacylglycerols and sterol esters surrounded by a monolayer of phospholipids

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8
Q

perilipins

A

family of proteins that coats the surface of lipid droplets to restrict access to the content of lipid droplets

prevent untimely lipid mobilization

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9
Q

Mobilization of Triacylglycerols Stored in Adipose Tissue occurs when -

What triggers changes that open the lipd droplet to the action of three cytosolic lipases?

A
  • mobilization occurs when hormones (glucagon and epinepherine) signal the need for metabolic energy
  • PKA triggers changes that open the lipid droplet to the action of three cytosolic lipases
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10
Q

free fatty acids, FFAs

A

fatty acids released by lipases

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11
Q

serum albumin

A

blood protein that noncovalently binds and transports FFAs to target tissues

makes up ~½ of the total serum protein

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12
Q

most of the biologically available energy of triacylglycerols resides in

A

their three long-chain fatty acids

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13
Q

phosphorylates glycerol to form glycerol 3-phosphate in the entry of glycerol into the glycolytic pathway

A

glycerol kinase

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14
Q

glyceraldehyde 3-phospbate can enter

A

glycolysis

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15
Q

Fatty acids are activated and transported into

A

mitochondria

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16
Q

small (< _____ carbons) fatty acids diffuse freely across mitochondrial membranes

A

<12 carbons

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17
Q

Transports long-chain fatty acids (containing 14+ carbons) through the mitochondrial membrane

A

carnitine shuttle

  • requires activation to a fatty acyl-CoA and
  • attachment to carnitine
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18
Q

fatty acyl-CoA synthetase

A

isozymes present in the outer mitochondrial membrane that activate the fatty acid by conversion to fatty acyl-CoA thioesters

fatty acid + CoA + ATP ⇄

fatty acyl-CoA + AMP + PPi

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19
Q

compound that transports fatty acyl-CoAs destined for mitochondrial oxidation across the inner mitochondrial membrane

A

carnitine

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20
Q

acyl-carnitine/carnitine cotransporter

A
  • allows the passive transport of the fatty acyl-carnitine ester
  • moves one carnitine into the intermembrane space as one fatty acyl-carnitine moves into the matrix
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21
Q

_____ pools of coenzyme A located ______

A

2; cytosol and mitochondria

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22
Q

coenzyme A in the mitochondrial matrix is largely used in:

A

oxidative degradation of pyruvate, fatty acids, and some amino acids

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23
Q

coenzyme A in the cytosol is used in the biosynthesis of

A

fatty acids

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24
Q

electron carrier that accepts electrons from FADH2

A

electron transfer flavoprotein (ETF)

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25
Q

flavoprotein that accepts electrons from ETF

A

ETF:ubiquinone oxidoreductase

passes electrons through ubiquinone into the mitochondrial respiratory chain

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26
Q

a multienzyme complex associated with the inner mitochondrial membrane that catalyzes steps 2-4 of the β-oxidation pathway for fatty acyl chains of 12+ carbons

allows efficient substrate channeling

A

trifunctional protein (TFP)

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27
Q

TFP is a ________ of alph4beta4 subunits

A

heterooctamer

α subunits contain enoyl-CoA hydratase and β-hydroxyacyl-CoA dehydrogenase activity

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28
Q

severe acidification of the blood and urine resulting from accumulated propionyl-CoA in the mitochondria being released to the blood as propionate

uses the carnitine shuttle

A

propionic acidemia

occurs in ~ 1 in 100,000 babies

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29
Q

the first intermediate of cytosolic fatty acid synthesis

blocks entry of fatty acids into mitochondria to prevent fultile cycling

A

malonyl-CoA

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30
Q

Oxidation of a Polyunsaturated Fatty Acid requires:

A

enoyl-CoA isomerase and 2,4-dienoyl-CoA reductase

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31
Q

β oxidation in peroxisomes has four steps:

peroxisomes = organelles found in plants and animals

A
  • dehydrogenation
  • addition of water to the resulting double bond
  • oxidation of the β-hydroxyacyl-CoA to a ketone
  • thiolytic cleavage by coenzyme A
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32
Q

characterized by an inability to make peroxisomes

individuals lack all metabolism related to peroxisomes

A

Zellwger syndrome

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33
Q

characterized by the inability of peroxisomes to oxidize very-long-chain fatty acids

due to the lack of a functional transporter in the peroxisomal membrane

A

X-linked adrenoleukodystrophy (XALD)

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34
Q

a long-chain fatty acid with methyl branches that is derived from the phytol side chain of chlorophyll

the methyl group on the β carbon makes β oxidation impossible

A

phytanic acid

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35
Q

refsum disease

A

results from a genetic defect in phytanoyl-CoA hydroxylase

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36
Q

catalyzes the oxidation of D-β-hydroxybutyrate to acetoacetate in extrahepatic tissue

A

D-β-hydroxybutyrate dehydrogenase

37
Q

Ketone bodies are used as fuel in all tissues except

A

liver

the liver lacks β-ketoacyl-CoA transferase

the liver is a producer of ketone bodies, not a consumer

38
Q

α oxidation

A

removes a single carbon from the carboxyl end of the fatty acid

converts branched fatty acids to products that can undergo β oxidation to yield acetyl-CoA and propionyl-CoA

39
Q

Two pools of fatty acyl-CoA

One pool is in the _______ and the other is in __________

A

cytosol; mitochondria

40
Q

fatty acyl-CoA in the mitochondrial matrix can be used for

A

oxidation and ATP production

conversion to the carnitine ester commits it to oxidation

41
Q

fatty acyl-CoA in the cytosolic pool can be used for

A

membrane lipid synthesis

42
Q

the rate-limiting step for oxidation of fatty acids in mitochondria

A

carnitine-mediated entry (carnitine shuttle)

43
Q

inhibits carnitine acyltransferase 1 and prevents the simultaneous synthesis and degradation of fatty acids

A

malonyl-CoA, the first intermediate in fatty acid synthesis

44
Q

Step 1 of Fatty Acid Oxidation

A

β oxidation

fatty acids undergo oxidative removal of successive two-carbon units in the form of acetyl-CoA

45
Q

Stage 2 of Fatty Acid Oxidation

A
  • oxidation of acetyl-CoA groups to CO2 in the citric acid cycle
    • occurs in the mitochondrial matrix
    • generates NADH, FADH2, and one GTP
46
Q

Stage 3 of Fatty Acid Oxidation

A

electron transfer chain and oxidative phosphorylation

generates ATP from NADH and FADH2

47
Q

flavoprotein with tightly bound FAD that catalyzes the dehydrogenation of fatty acyl-CoA to yield a trans-∆2-enoyl-CoA

A

acyl-CoA dehydrogenase

48
Q

Acyl-CoA Dehydrogenase Isozymes

A
  • isozymes are specific for fatty-acyl chain lengths:
    • VLCAD (inner mitochondrial matrix): 12-18 carbons
    • MCAD (matrix): 4-14 carbons
    • SCAD (matrix): 4-8 carbons
49
Q

Hydration of the Trans-∆2-Enoyl-CoA

_________catalyzes the addition of water to the double bond of the trans-∆2-enoyl-CoA to form….

A

enoyl-CoA hydratase

…L-β-hydroxyacyl-CoA (3-hydroxyacyl-CoA)

50
Q

catalyzes the dehydrogenation of L-β-hydroxyacyl-CoA

….to form

A

β-hydroxyacyl-CoA dehydrogenase

…

β-ketoacyl-CoA

enzyme is specific for the L stereoisomer

51
Q

NADH dehydrogenase (Complex I)

A

electron carrier of the respiratory chain

accepts electrons from the NADH formed in the β-hydroxyacyl-CoA dehydrogenase reaction

52
Q

catalyzes the reaction of β-ketoacyl-CoA with free coenzyme A to yield….

A

acyl-CoA acetyl-transferase (thiolase)

…acetyl CoA and a fatty acyl-CoA shortened by two carbons

53
Q

β subunits contain ______ activity

A

thiolase activity

54
Q

The Four β-Oxidation Steps Are Repeated to yield

A

Acetyl-CoA and ATP

55
Q

The Overall Reaction for Stage 1 of
β Oxidation

A

palmitoyl-CoA + 7CoA + 7FAD + 7NAD+ + 7H2O ⟶

8 acetyl-CoA + 7FADH2 + 7NADH + 7H+

56
Q

each FADH2 donates a pair of electrons to ETF

generates -

each NADH donates a pair of electrons to the mitochondrial NADH dehydrogenase

generates -

in total, _______ are formed for each pass through Beta oxidation

A

FADH2 - 1.5 molecules of ATP

NADH - 2.5 molecules of ATP

4 ATP are formed

57
Q

The Overall Reaction for Stage 1 of
β Oxidation, Including Electron Transfers and Oxidative Phosphorylations

A

palmitoyl-CoA + 7CoA + 7O2 + 28Pi + 28ADP ⟶

8 acetyl-CoA + 28ATP + 7H2O

58
Q

The Overall Reaction for the Complete Oxidation of Palmitoyl-CoA to CO2 and H2O

A

palmitoyl-CoA + 23O2 + 108Pi + 108ADP ⟶

CoA + 108ATP + 16CO2 + 23H2O

59
Q

enoyl-CoA hydratase cannot catalyze the addition of H2O to a cis double bond

oxidation of unsaturated fatty acids requires two additional enzymes:

A
  • enoyl-CoA isomerase (converts cis double bonds to trans)
  • 2,4-dienoyl-CoA reductase (reduces cis double bonds)
60
Q

acetone, acetoacetate, and D-β-hydroxybutyrate

formed from acetyl-CoA in the liver

A

ketone bodies

acetoacetate and D-β-hydroxybutyrate are transported to extrahepatic tissues and converted to acetyl-CoA to be oxidized in the citric acid cycle

61
Q

oxidation of a monounsaturated fatty acid requires

A

an enoyl-CoA isomerase

62
Q

isomerizes the cis-∆3-enoyl-CoA to the trans-∆2-enoyl-CoA

A

∆3,∆2- enoyl-CoA isomerase

63
Q

beta oxidation requires double bond between

A

C2 and C3

64
Q

Complete oxidation of odd-number fatty acids require _______extra reactions

A

three

65
Q

three-carbon compounds formed by cattle and other ruminant animals during carbohydrate fermentation

A

propionate (CH3–CH2–COO−)

66
Q

odd-number fatty acids are oxidized by the β-oxidation pathway to yield acetyl-CoA and a molecule of

A

propionyl-CoA

67
Q

_____catalyzes the carboxylation of propionyl-CoA to form D-methylmalonyl-CoA

cofactor:

A

propionyl-CoA carboxylase

requires the cofactor biotin

68
Q

Oxidation of Propionyl-CoA Step 2

__________catalyzes the epimerization of D-methylmalonyl-CoA to its L stereoisomer

A

methylmalonyl-CoA epimerase

69
Q

Oxidation of Propionyl-CoA – Step 3

_________catalyzes the intramolecular rearrangement of L-methylmalonyl-CoA to form succinyl-CoA (which can enter the citric acid cycle)

requires:

A

methylmalonyl-CoA mutase

requires: 5′-deoxyadenosylcobalamin, or coenzyme B12, as its coenzyme

70
Q

catalyzes the enzymatic condensation of two acetyl-CoA molecules to form acetoacetyl-CoA

reversal of the last step of β oxidation

A

thiolase

71
Q

Transcription factors turn on the synthesis of proteins for __________

A

lipid catabolism

72
Q

transcription factors that affect many metabolic processes in response to a variety of fatty acid–like ligands

A

PPAR family of nuclear receptors

73
Q

stimulates the synthesis of enzymes required in β oxidation when there is an increased demand for energy from fat catabolism

A

PPARα

74
Q

acyl-CoA dehydrogenase isozyme that acts on fatty acids of 4-14 carbons

A

medium-chain acyl-CoA dehydrogenase (MCAD)

75
Q

individuals with two mutant MCAD alleles cannot oxidize fatty acids of_______

symptoms includes:

A

6-12 carbons

symptoms include fatty liver, high blood levels of octanoic acid (8:0), coma, and death

76
Q

Other Genetic Defects in Fatty Acid Transport or Oxidation

A
  • loss of the long-chain β-hydroxyacyl-CoA dehydrogenase activity of the trifunctional protein, TFP
  • defects in the α or β subunits that affect all three activities of TFP
77
Q

catalyzes the condensation of acetoacetyl-CoA with acetyl-CoA to form β-hydroxy-β-methylglutaryl-CoA (HMG-CoA)

A

HMG-CoA synthase

78
Q

Differences Between the Peroxisomal and Mitochondrial Pathways

A

in peroxisomes, the flavoprotein acyl-CoA oxidase that introduces the double bond passes electrons directly to O2, producing H2O2

the enzyme catalase cleaves H2O2 to H2O and O2

the peroxisomal system is much more active on very-long-chain fatty acids and branched-chain fatty acids

79
Q

catalyzes the cleavage of HMG-CoA to free acetoacetate and acetyl-CoA

A

HMG-CoA lyase

80
Q

catalyzes the decarboxylation of acetoacetate to aceton

A

acetoacetate decarboxylase

81
Q

catalyzes the reversible reduction of acetoacetate to D-β-hydroxybutyrate

A

D-β-hydroxybutyrate dehydrogenase

82
Q

catalyzes the activation of acetoacetate

A

β-ketoacyl-CoA transferase

acetyl-CoA enters the citric acid cycle

83
Q

Ketone Bodies are Overproduced in _______ and during ________

A

Diabetes; starvation

the accumulation of acetyl-CoA accelerates formation of ketone bodies

extrahepatic tissues do not have the capacity to oxidize them all

84
Q

lowered blood pH

can be caused by increase levels of acetoactate, and D-β-hydroxybutyrate

A

acidosis

85
Q

high levels of ketone bodies in the blood and urine

A

ketosis

86
Q

condition when ketosis and acidosis are combined

A

ketoacidosis

87
Q

Individuals with untreated diabetes have high _______ levels

A

acetone

individuals with untreated diabetes produce large quantities of acetoacetate

acetone formed from the decarboxylation of acetoacetate is volatile

imparts a characteristic odor to the breath

88
Q

catalyzes the decarboxylation of acetoacetate to acetone

A

acetoacetate decarboxylase

M1 (48 decks)

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