Lecture 25 - Lipid Metabolism Flashcards

1
Q

for mammals, what is 5-25% of body weight due to?

A

fat and lipids

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2
Q

for mammals, what is 90% of their weight?

A

triaclglycerols

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3
Q

how is fat stored in humans?

A
  • adipocytes

- primarily subcutaneous + abdominal cavity

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4
Q

are fats soluble?

A

highly insoluble

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5
Q

how is fat digested?

A

by enzumes

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6
Q

where is fat transported?

A

through plasma

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7
Q

what is the process of fat absorption?

A

cellular uptake

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8
Q

what is a result of fat being so insoluble?

A

-digestion, transport + absorption are problematic

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9
Q

what is the digestion of fat facilitated by?

A

bile salt in the intestines

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10
Q

what do bile salts do?

A

-emulsifying fat to aid in their hydrolysis

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11
Q

what does pancreatic lipase do?

A

breaks down fat

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12
Q

what does pancreatic lipase generate?

A

-mixture of glycerol, fatty acids, mono + di-acylglycerols

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13
Q

fats are aggregated by certain ______ into ________ called _______

A

proteins
water-soluble units
lipoproteins

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14
Q

where are lipoproteins transported?

A

through plasma

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15
Q

how are lipoproteins divided?

A

by size, composition, and morphology

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16
Q

what are lipoproteins divided into?

A

-chylomicrons and lipoproteins of various densities

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17
Q

what are dietary triacylglycerols carried by?

A

lipoproteins

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18
Q

what are dietary triaclyglycerols targed by?

A

cell surface receptors

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19
Q

what happens after dietary triaclyglycerols have been targeted by cell surface receptors?

A
  • they are hydrolyzed by lipoprotein lipase

- transported into cytosol

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20
Q

how are triacylglycerols in adipose cells mobilized?

A
  • by their hydrolysis in the cytosol

- using a hormone-sensitive lipase

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21
Q

where are the fatty acids released?

A
  • into the blood

- carried by 66-kD protein albumin

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22
Q

fatty acids are ____ before they are degraded

A

activated

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23
Q

what is required to activate fatty acids?

A
  • ATP and CoA

- catalyzed by acyl-CoA synthetase

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24
Q

What is the result of the hydrolysis of PPi for the activation of fatty acids?

A

pushes quilibriium far to the right

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25
Q

what is the reaction of fatty acid activation?

A

Fatty acid + CoA + ATP <> Acyl-CoA + AMP + PPi

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26
Q

why are there different acyl-CoA synthetases?

A

-specific to fatty acids of different length acyl chains

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27
Q

where does fatty acid activation happen?

A

-in the cytosol

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28
Q

where does the rest of the oxidation of fatty acid occur?

A

mitochondria

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29
Q

where does the degredation of fatty acids take place?

A

mitochondria

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30
Q

what happens to the acyl group during fatty acid degradation?

A

-acyl group is transferred to a carnitine

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31
Q

what happens to the carnitine during fatty acid degradation?

A

transported into the mitochrondrial matrix by a carnitine transporter
(unloads cargo on inside then carnitine shuttled back out)

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32
Q

what finally happens during fatty acid degradation?

A

-fatty acid then oxidized completely into acetyl-CoA

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33
Q

what kind of pathway is fatty acid degradation?

A

spiral pathway

beta oxidation of fatty acids

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34
Q

what is a spiral pathway?

A
  • each round the acyl chain is shortended by 2Cs

- splitting out acetyl-CoA

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35
Q

what kind of reaction does the spiral fatty acid degradation pathway involve?

A
  • oxidation reaction

- occurs 2 C away from C=o group (beta)

36
Q

what can be done with each acetyl-CoA?

A

each acetyl-CoA can be fed into the citric acid cycle

37
Q

what does beta oxidation itself generate?

A

1 NADH

1 QH2

38
Q

what does the degradation of unsaturated acyl chains require?

A

isomerization and reduction

39
Q

what are the 4 (different) steps of degredation of unsaturated fatty acids?

A
  1. after 3 rounds, oxidation of linoleate must be isomerized into trans form
  2. next round proceeds as usual
  3. reductase (which requires NADPH) used to remove one double bond when another cis double bond is encountered
  4. isomerase to relocate double bond
40
Q

what is a major difference in the beta oxidation of odd-numbered-chain fatty acids?

A

-acyl chains with odd number of carbons produces propionyl-CoA instead of acetyl-CoA

41
Q

how is the beta oxidation of odd-numbered-chain fatty acids remedied?

A
  • extend it using a carboxylase

- turn it into a citric cycle intermediate

42
Q

where does some fatty acid oxidation occur?

A

in peroxisomes

43
Q

what is a peroxisome?

A

single-membrane bound

44
Q

in plants where does all fatty acid oxidation take place?

A

in peroxisomes and glyoxysomes

45
Q

where does most mammalian fatty acid oxidation occur?

A

mitochodnria

46
Q

what happens to electrons in peroxisomal beta oxidation?

A

-electrons removed are deposited into O2 to make peroxide H2O2

47
Q

what is the peroxisome responsible for?

A

shortening very long acyl chains

48
Q

what else is carried out in peroxisomes?

A

branched-chain beta oxidation

49
Q

where does synthesis of fatty acids occur?

A

solely i the cytosol on the smooth ER

50
Q

in the synthesis of fatty acids, starting from acetyl-CoA ____ are added at at a time

A

2 Cs

51
Q

the ______ pathway for fatty acids is very different from the beta oxidation and uses different ________

A

anabolic

enzymes

52
Q

what is the key coenzye in fatty acid synthesis?

A

acyl-carrier (AC) arm, phosphorylated to a Ser on the enzyme fatty acid synthase

53
Q

how does fatty acid synthesis start?

A

with the carboxylation of Acetyl-CoA

54
Q

what is the first step of fatty acid synthesis?

A

-elongating the C2 in acetyl-CoA by carboxylase

55
Q

what are the first 3 steps of fatty acid synthesis?

A
  1. 1 ATP required to load CO2 onto biotin
  2. malonyl group transferred to ACP
  3. Malonyl-ACP adds two carbons at a time to the chain using a mechanism similar to pyruvate carboxylase
56
Q

what catalyzes all 7 steps of fatty acid synthesis?

A

fatty acid synthase

57
Q

every step in fatty acid synthesis is carried out on a __________

A

single multi-function enzyme

58
Q

where are the 2NADPH needed for fatty acid synthesis supplied by?

A

pentose phosphate pathway

59
Q

during fatty acid synthesis what happens each time malonate is loaded onto ACP?

A

1 ATP is required (to carboxylate biotin)

60
Q

how do you synthesize a C16 palmitate?

A

7 rounds of the fatty acid synthesis reaction must e repeated

61
Q

what is the total energy cost of fatty acid synthesis?

A

7 ATP + 14 NADPH

62
Q

fatty acid synthase can only synthesize saturated acyl chains up to _____

A

C16

63
Q

some sphingolipids contain ____ and ____ fatty acids

A

C22 and C24

64
Q

what is arachidonic acid?

A
  • precursor to the eicosanoids
  • C20 fatty acid
  • multiple unsaturated C=C bonds
65
Q

how are double bonds added to C16 palmitate?

A

by desaturase enzymes via a dehydrogenation rxn (an oxidation) where electrons are transferred to O2 making H2O

66
Q

what can elongation be catalyzed by?

A

elongase

67
Q

what is the result of mammals not being able to introduce a C=C bond beyond C9?

A

fatty acids like linoleate must be acquired in their diet for these so-called “essential fatty acids”

68
Q

does the brain metabolize fat for energy?

A

no

69
Q

why does the brain not metabolize fat for energy?

A

-lipids do not cross the blood/brain barrier

70
Q

how does the brain get its energy?

A

relies on glucose

71
Q

what are ketone bodies?

A
  • class of molecules synthesized from acetyl-CoA

- supplemental source of energy in ketogenesis

72
Q

what are ketone bodies?

A
  • water soluble

- can pass through into central nervous system

73
Q

how are triacylglycerols and phospholipids synthezied?

A

-from acyl-CoA groups using a citric cycle intermediate

74
Q

how are fatty acid acyl groups activated in triacylycerosl?

A

activated by acyl-CoA syntheses

fatty acid + CoA + ATP ,. acyl-CoA + AMP + PPi

75
Q

how does cholesterol synthesis begin?

A
  • with acetyl-CoA

- in a reaction that is similar to the first step in ketogenesis

76
Q

where does cholesterol synthesis occur?

A

in the cytosol

77
Q

what does mevalonate acquire in cholesterol synthesis?

A
  • 2 PO4

- is decarboxylated to produce a C5 molecule

78
Q

what is isopentenyl pyrophosphate?

A

-precursor to cholesterol + other isoprenoids

79
Q

what is the final step of cholesterol synthesis?

A
  • 6 isopentenyl pyrophosphates are condensed together

- forming a C30 compound squalene

80
Q

what is cholesterol synthesis inhibited by?

A

-statins

81
Q

what do statins bind to?

A

-they bind irreversibly to HMG-CoA reductase

82
Q

what are another effect of statins?

A
  • also shut off the synthesis of other isoprenoids

- long-term use carries adverse affects

83
Q

what are the 4 ways that cholesterol are used?

A
  1. membrane additive
  2. precursor to bile acids (cholate)
  3. precursor to steroid hormones (testosterone + estrogen)
  4. acylated to form a cholesteryl ester for storage or for packaging in VLDL
84
Q

where can cells acquire cholesterol from?

A

cells can synthesize/acquire cholesterol from circulating LDL

85
Q

what are HDL essential for?

A

essential for removing excess cholesterol from cells