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Danielle- MCM Test 1 > Lecture 5 & 6: Fatty Acid Metabolsim > Flashcards

Lecture 5 & 6: Fatty Acid Metabolsim Flashcards

1
Q

Synthesis of FA’s involves a series of reactions all of which occur on the FA synthase complex. Which of the following most accurately represents the sequence of these reactions? A) Condensation, reduction, dehydration, reduction B) Condensation, reduction, hydration, reduction C) Condensation, oxidation, dehydration, oxidation D) Condensation, oxidation, hydration, oxidation

A

A) Condensation, reduction, dehydration, reduction

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2
Q

A pharmaceutical company is developing a new drug that inhibits FA synthesis in obese (BMI >30) patients. The drug is supposed to prevent the insulin-dependent activation of the rate limiting enzyme of FA synthesis. TO check the efficacy of drug candidates in cell cultures, the inhibition of which of the following enzymes would serve as a suitable marker? A) Long-chain acyl CoA dehydrogenase B) protein phosphatase C) Glycogen phosphorylase D) Protein kinase B (PKB) E) Protein Kinase A (PKA)

A

B) Protein phosphatase

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3
Q

The correct sequence of steps for shortening of a fatty acyl CoA by two carbons is: A) dehydration, hydration, oxidation, and thiolytic cleavage B) Thiolytic cleavage, hydration, oxidation, and acylation C) Oxidation, hydration, oxidation, and thiolytic cleavage D) Oxidation, hydration, dehydration, and thiolytic cleavage E) Hydration, oxidation, oxidation, and thiolytic cleavage

A

C) Oxidation, hydration, oxidation, and thiolytic cleavage

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4
Q

Beta-oxidation of an odd-chain FA produces several 2C and one 3C molecules. The after enters the TCA cycle in the form of which compound? A) Citrate B) Isocitrate C) Alpha-ketoglutarate D) Succinyl CoA E) Malate

A

D) Succinyl CoA

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5
Q

What is a glycerolipid?

A

A fatty acid derivative with a glycerol backbone (Mono, di, and tri- acylglycerides

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6
Q

What is a glycerophospholipid?

A

2 fatty acids attached to a glycerol backbone - Phosphate is esterified with a head group

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7
Q

What is a major source of carbon for fatty acid synthesis?

A

Dietary carbons -> need carbs in diet to synthesize fats

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8
Q

Where does fatty acid synthesis primarily occur?

A

IN the liver

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9
Q

Fatty acid synthesis primarily occurs in the liver but can also occur in what 4 locations?

A

Adipose tissue, brain, kidneys, and lactating mammary glands

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10
Q

What is the end product of fatty acid synthesis in humans?

A

Palmitic acid -> 16C

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11
Q

Where does phase 1 of fatty acid synthesis occur?

A

made in mito but needed in cytoplasm

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12
Q

What is the goal of phase 1 of fatty acid synthesis?

A

To get acetyl CoA into the cytosol

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13
Q

How does acetyl CoA get to the cytosol in fatty acid synthesis?

A

Citrate shuttle

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14
Q

What ate the steps of the citrate shuttle from oxaloacetate back to oxaloacetate?

A

Oxaloacetate + acetyl coA -> citrate -> citrate in cytoplasm -> oxaloacetate + acetyl coA

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15
Q

In the first step of the carnitine shuttle, what enzyme is used for the condensationof acetyl CoA and oxaloacetate to form citrate?

A

Citrate synthase

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16
Q

During the carnitine shuttle pathway, what enzyme converts citrate back to acetyl coA and oxaloacetate?

A

Citrate lyase

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17
Q

What is the purpose of phase 2 of fatty acid synthesis?

A

Synthesis of malonyl CoA

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18
Q

What is the rate limiting step and enzyme of fatty acid synthesis?

A

Phase II; acetyl CoA carboxylase

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19
Q

What Cofactor is needed for acetyl coA carboxylase in fatty acid synthesis?

A

Biotin

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20
Q

What enzyme is used to convert acetyl CoA to malonyl coA in fatty acid synthesis and what cofactor is needed?

A

Acetyl CoA carboxylase; biotin

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21
Q

What is the inactive and active form of malonyl coA?

A

Dimeric form = inactive Polymeric form = active

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22
Q

How many carbons are in malonyl coA?

A

3

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23
Q

____________ is a regulator. It inhibits carnitine acyltranserase, the rate limiting step in FA degradation

A

Malonyl CoA (substrate for fatty acid synthase (FAS)) - This prevents FA synthesis and degradation from occurring simultaneously

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24
Q

What is the purpose of phase 3 of fatty acid synthesis?

A

Fatty acid chain synthesis

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25
Q

What enzyme is used to convert malonyl CoA to Palmitate in fatty acid synthesis?

A

Fatty acid synthase

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26
Q

The reactions of fatty acid synthesis occur on the _________ __________ __________ complex

A

Fatty Acid Synthase

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27
Q

Where is the fatty acid synthase complex located?

A

Cytoplasm

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28
Q

Describe the structure of fatty acid synthase

A
  • Large multi-enzyme complex - Composedof 2 identical dimers - 2 dimers arranged head to tail - Each has 7 enzyme activities and an acyl carrier protein (ACP)
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29
Q

What is the flexible arm of ACP made of?

A

Phosphopatetheine

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30
Q

List the basic reactions of fatty acid synthesis

A

Activation -> Condensation -> Reduction -> Dehydration -> Reduction -> Product release and cycle repeats

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31
Q

What are sources of NADPH for fatty acid synthesis?

A

Malic enzyme and PPP

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32
Q

Where does acetyl coA bind in fatty acid synthesis?

A

To cysteine on FAS

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33
Q

Where does malonyl coA bind during fatty acid synthesis?

A

Cysteine on ACP

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34
Q

What directly stimulates ATP citrate lyase in fatty acid synthase?

A

Phosphorylation

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35
Q

What induces gene expression of ATP citrate lyase in fatty acid synthesis?

A

Glucose/insulin

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36
Q

What counteracts gene expression of ATP citrate lyase in fatty acid synthesis??

A

PUFAs and leptin

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37
Q

What allosterically stimulates acetyl CoA carboxylase in fatty acid synthesis?

A

Citrate

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38
Q

What allosterically inhibits acetyl coA carboxylase?

A

Long chain fatty acids palmitate

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39
Q

Does phosphorylation of acetyl coA carboxylase turn it on or off?

A

Off - Dephosphorylation turns it on

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40
Q

________ dephosphorylates acetyl CoA carboxylase, therefore activating it, via activation of protein phosphatase

A

Insulin

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41
Q

__________ and ___________ phosphorylate acetyl CoA carboxylase, therefore inhibiting it, via protein kinase A

A

Epinephrine and glucagon

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42
Q

_________ phosphorylates acetyl coA carboxylase, therefore inhibiting it, via activation of AMP kinase (energy sensor)

A

AMP

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43
Q

What kind of diet is gene expression of acetyl coA carboxylase up-regulated by?

A

High carb/low fat diet

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44
Q

What allosteric effect does the presence of phosphorylated sugars have on FAS?

A

Increase activity

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45
Q

What 2 hormones increase synthesis of FAS?

A

Insulin and glucocorticoids

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46
Q

What type of diet increases FAS synthesis?

A

High carb/low fat

47
Q

What type of diet lowers synthesis of FAS?

A

High fat diets - Starvation too!

48
Q

What effect does high PUFA content have on FAS?

A

Suppresses its synthesis

49
Q

Where does elongation of FAs occur?

A

Smooth endoplasmic reticulum or mitochondria

50
Q

What type of cells need longer fatty acids (C18-C24)?

A

Brain cells

51
Q

The SER pathway of FA elongation uses ___________ as carbon donor

A

Malonyl CoA

52
Q

Mitochondria pathway of FA elongation uses ________ as carbon donor

A

Acetyl CoA

53
Q

Desaturation of FAs introduces what?

A

Double bonds

54
Q

Where does desaturation of FAs occur?

A

SER

55
Q

What is desaturation of FAs catalyzed by?

A

Acyl CoA desaturases

56
Q

How many desaturases do humans have?

A

4 (Delta 4, 5, 6, and 9)

57
Q

T/F: FA with double bond beyond carbon 9 and 10 cant be synthesized in humans

A

T

58
Q

Dietary _______ induces expression of delta 9 desaturases, suppresses all others

A

Cholesterol

59
Q

Gene expression of desaturases is suppressed by what?

A

Dietary PUFAs

60
Q

Gene expression of desaturases is induced by what?

A

Insulin

61
Q

Linoleic acid is what type of essential FA?

A

Omega 6

62
Q

Linolenic acid is what type of essential FA?

A

Omega 3

63
Q

Linoleic acid is used to make ___________ acid

A

Arachidonic - Precursor for eicosanoids (prostaglandins, eukotrienes, and thromboxanes)

64
Q

Linolenic acid is used to make _____________ and ________________ acid

A

Eicosapentanoic (EPA) and DHA

65
Q

The outer mitochondrial membrane is not permeable to what?

A

FA

66
Q

The inner mitochondrial membrane is not permeable to what?

A

FACoA

67
Q

What is the purpose of phase 1 of fatty acid oxidation?

A

Transport of free fatty acids into the mitochondrial matrix via carnitine shuttle

68
Q

Where does phase one of fatty acid oxidation occur?

A

Cytosol

69
Q

Where does phase 2 of fatty acid oxidation occur?

A

In mitochondrial matrix - This is beta oxidation

70
Q

What is the purpose of phase 2 of fatty acid oxidation?

A

Beta oxidation of FAs

71
Q

What can diffuse into mitochondria in terms of fatty acids?

A

Short and medium chain FAs

72
Q

What needs to be actively transported into mitochondria in terms of fatty acids?

A

Long chain and very long chain FAs

73
Q

Where are very long chain FAs oxidized to LCFAs before using carnitine shuttle?

A

Peroxisomes

74
Q

What enzyme is used in phase one (activation) of fatty acid oxidation?

A

Fatty acyl CoA synthetase

75
Q

Where is fatty acyl CoA synthetase located?(FA oxidation)

A

Outer mito-membrane - Reaction catalyzed on cytoplasmic side of membrane

76
Q

What type of bond is formed between FAs and CoA to form FACoA during FA oxidation?

A

Thioester bond

77
Q

What s the rate limiting enzyme in FA degradation?

A

Carnitine palmitoyltransferase I (CPT-I)

78
Q

Where is CPT-I located? (FA oxidation)

A

Intermembrane space

79
Q

What is the role of CPT-I in FA oxidation?

A

Transfers fatty acyl from FA-CoA to carnitine forming FA-carnitine

80
Q

What is CPT-I in FA oxidation inhibited by?

A

Malonyl CoA

81
Q

There are 4 steps of beta oxidation. The first step is oxidation using what enzyme?

A

Acyl CoA dehydrogenase (ACAD)

82
Q

What are the 4 types of ACADs

A

Short chain (SCAD) Medium chain (MCAD) Long chain (LCAD) Very long chain (LCAD)

83
Q

Steps 3-4 of beta oxidation use enoyl CoA hydratase, beta hydroxy acyl CoA dehydrogenase, and acyl CoA acyl transferase or ketothiolase. These 3 enzymes together are called what?

A

MTFP (mitochondrial trifunnctional protein)

84
Q

Catabolism of palmitic acid gives ______ ATP

A

129

85
Q

Acetyl CoA generates ______ ATP

A

12

86
Q

Odd numbered FAs are metabolized until _____________ remains

A

Propionyl CoA (3C)

87
Q

what enzyme is used to convert propionyl coA to methylmalonyl CoA when degrading odd numbered FAs?

A

Propionyl CoA carboxylase

88
Q

What enzyme generates succinyl CoA from methylmalonyl CoA during degradation of odd numbered FAs?

A

Methylmalonyl CoA mutase

89
Q

What product of the degradation of odd numbered FAs enters TCA?

A

Succinyl CoA

90
Q

VLCFAs are more than _____ carbons

A

20

91
Q

How are unsaturated FAs degraded?

A

1) Reductase reduces double bond 2) Isomerases moves the disruptive bond

92
Q

How long does VLCFA oxidation occur in peroxisome?

A

Until you get a 20 carbon FA

93
Q

What does VLCFA degradation in peroxisomes produce?

A

H2O2 - Peroxide can be toxic so catalase converts the hydrogen peroxide into water and oxygen which arent toxic

94
Q

What enzyme oxidizes the first step of VLCFA oxidation?

A

Acyl CoA oxidase

95
Q

_________ is an analog of lysine, not synthesized in the body, and rich in skeletal muscle

A

Carnitine - Carnitine deficiency is common in strict vegetarians **Without carnitine you dont get beta oxidation**

96
Q

An autosomal recessive disorder of FA beta oxidation that impairs the breakdown of MCFAs is due to a deficiency of what enzyme?

A

MCAD

97
Q

Patients with an MCAD deficiency depend on what as an energy source?

A

Glucose

98
Q

__________ deficiency leads to secondary carnitine deficiency due to excessive excretion of MCA carnitines in urine

A

MCAD - C8 FA accumulates in liver and interferes with urea cycle leading to elevated levels of ammonia

99
Q

Gluconeogenesis is impaired in MCAD deficiency die to low activity of what enzyme?

A

Pyruvate carboxylase (due to low ATP and acetyl coA)

100
Q

Ketone bodies are water-soluble and acidic compounds. What are the three ketone bodies/

A

Acetoacetate Beta hydroxybutyrate Acetone

101
Q

Where are ketone bodies produced?

A

IN LIVER ONLY

102
Q

Where in hepatocytes does synthesis of ketone bodies occur?

A

mitochondrial matrix

103
Q

What three organs utilize ketone bodies

A

Brain (only when starving), muscle and kidneys - RBCs cannot utilize ketone bodies for energy

104
Q

1 acetate yields _____ ATP

A

23 -> 24 from acetyl CoA, minus 1 from activation of acetoacetate

105
Q

1 beta hydroxybutyrate yields _____ ATP

A

26 -> 3 from NADH, 24 from 2 acetyl CoA , minus 1 from activationof acetoacetate

106
Q

What is the primary energy source during the first few hours of fasting?

A

Blood glucose followed by glycogen stored in muscle and liver - Next would be gluconeogenesis in liver

107
Q

What is the primary energy source after 1 day of fasting?

A

TAGs stored in adipose tissue - TAGs broken down to release FA which undergo beta oxidation

108
Q

What s the primary energy source after 3 days of fasting?

A

Ketone bodies made in liver and proteins in muscles are broken down - Glycerol from TAGs and glucogenic AAs from proteins enter gluconeogenesis -> supplies energy to brain and RBCs

109
Q

What is the primary energy source after 1-2 weeks of starvation?

A

Brain switches to ketone bodies as major energy source

110
Q

What s the primary energy source after 2-3 months of starvation?

A

TAGs depleted, proteins main source -> coma and death

111
Q

__________ ____________ occurs in fasting, during pregnancy and in babies, and after prolonged exercise and is a mild to moderate increase in ketone bodies

A

Physiological ketosis

112
Q

______________ _____________ occurs when glucagon/insulin ratio is increased, favoring FA breakdown.

A

Pathological ketoacidosis

113
Q

What are the steps of diabetic ketosis?

A

Glucose cant enter liver or adipose tissue: 1) OAA level drops 2) CAC 3) Free FAs are released from adipose tissue 4) Ketone bodies form 5) Blood pH drops 6) Coma and death result

Danielle- MCM Test 1 (12 decks)

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