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Nutritional Biochem 2 > CoQ10 and Omegas > Flashcards

CoQ10 and Omegas Flashcards

1
Q

How many isoprene units are there in CoQ10?

A

4 C + a methyl branch

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2
Q

Functional group of CoQ10?

A

quinone ring

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3
Q

What is the oxidized and reduced form of CoQ10?

A

oxidized: ubiquinone
reduced: ubiquinol –> majority

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4
Q

Increase in serum CoQ10 requires supp with?

A

100 mg/day

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5
Q

What is strongly lipophilic and mostly insoluble?

A

CoQ10

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6
Q

How is CoQ10 absorbed in SI?

A

slowly/incompletely using soluble passive diffusion

- absorption rate = 6 %

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7
Q

Conversion of ubiquinone –> ubiquinol occurs in?

A

enterocytes prior to lymphatic transport

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8
Q

What are the 3 enzymes that keep CoQ10 reduced?

A
  1. NADH cytochrome reductase
  2. NADH/PH oxidoreductase
  3. NADPH CoQ reductase
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9
Q

CoQ10 in the liver is packaged into?

A

VLDL’s

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10
Q

In plasma CoQ10 is carried by?

A

LDL’s

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11
Q

What formulations of CoQ10 are more bioavailable?

A

oil based solubilized (vs powder)

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12
Q

High dose of what vit interferes with CoQ10 absorption?

A

vitamin E

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13
Q

Does exogenous CoQ10 down-reg endogenous synthesis?

A

NO

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14
Q

Tissues synthesize CoQ10 from?

A

farnesyl diphosphate (FPP) and tyrosine

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15
Q

FPP is the precursor of?

A

DPP (decarprenyl prophosphate)

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16
Q

Trysoine is the precursor of?

A

4-hydroxybenoate

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17
Q

What is the fundamental building block of CoQ10?

A

mevalonate

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18
Q

What are the essential cofactors for CoQ10?

A

vitamin B6, iron, and magnesium

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19
Q

A missense mutation of the Coq2p gene causes a deficiency in what?

A

CoQ10

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20
Q

What type of cells hold the highest CoQ10 concentrations?

A

highly metabolically active (cardiac, skeletal m., kidney, liver)

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21
Q

50% of the body’s CoQ10 is localized where?

A

inner mitochondrial membrane

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22
Q

What is the primary rolls of CoQ10?

A
  • normal cellular respiration and ATP production

- intercellular antioxidant

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23
Q

What is CoQ10’s co-antioxidant?

A

vit E

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24
Q

What regenerates the CoQ10 radical?

A

dhydrolipoic acid (DHLA) and thioredoxin reductase

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25
Q

CoQ10 intake can spare what vitamin?

A

vit E

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26
Q

What molecule functions as a potent gene regulator?

A

CoQ10

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27
Q

What molecules can be conjugated with glucoronide?

A

CoQ10

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28
Q

Why do CoQ10 levels decrease with age?

A
  1. higher oxidative stress which uses more CoQ10

2. reduced enzymatic function

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29
Q

What organ is most susceptible to a CoQ10 deficiency?

A

heart

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30
Q

What molecules acts at the mitochondrial level to improve heart function and protect against LDL oxidation?

A

CoQ10

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31
Q

How does CoQ10 reduce BP?

A

quench free radicals that damage vasodilators such as nitric oxide

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32
Q

Both cholesterol and CoQ10 synthesis depend on what enzyme?

A

HMG-CoA reductase

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33
Q

What can block HMG-CoA reductase and lead to decreased CoQ10?

A

statins

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34
Q

What is the most serious statin-induced myopathy?

A

rhabdomyolysis

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35
Q

Supplementing with which molecule is recommended to prevent myopathic side effects from statin drugs?

A

CoQ10

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36
Q

What are the 3 forms of omega-3 fatty acids?

A

ALA, EPA, DHA

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37
Q

What are the conditionally essential fatty acids?

A

EPA and DHA

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38
Q

ALA is synthesized by?

39
Q

DHA concentrations are highest where?

A

retina and cerebral cortex

- EPA is low in all tissues

40
Q

ALA is converted to EPA and DHA in?

41
Q

Final B-oxidation of ALA occurs where?

A

peroxisome

42
Q

Linoleic acid goes to y-linolenic acid by what enzyme?

A

fatty acid desaturase 2

43
Q

Linoleic acid goes to y-linolenic acid by what enzyme?

A

^6 desaturase

44
Q

di-homo-y-linolenic acid goes to arachidonic acid by what enzyme?

A

^5 desaturase

45
Q

What is the rate limiting step in ALA conversion?

A

fatty acid desaturase 2

- decreases with age

46
Q

What is the rate limiting step in ALA conversion?

A

^6 desaturase

- decreases with age

47
Q

What is the most rapidly oxidized unsaturated FA?

48
Q

What is the most rapidly oxidized unsaturated FA?

49
Q

What competes with ALA for access to ^6 desaturase?

50
Q

Stearidonic acid elevates?

A

EPA, but not DHA

51
Q

What inhibits ^6 and ^5 desaturase and therefore reduces EPA and DHA?

52
Q

DHA supp raises what?

A

EPA

retro-conversion

53
Q

What found in fish is neurotoxic?

A

methylmercury

54
Q

Why do fish oil supp’s contain less mercury than fish?

A
  1. smaller fish are used
  2. mercury binds to protein
  3. distilling
55
Q

Farmed fish have lower mervury than wild but higher what?

A

dioxins, PCB, and chlordane

56
Q

There is a larger omega-3 to toxin ratio in farm or fresh fish?

57
Q

Markers for oxidative stress and redox balance, such as MDA, reduced vit C and E, and elevated catalase and glutathione peroxidase are affected by?

A

Oxidized lipids

58
Q

Which omega-3 are more suseptible to lipid oxidation?

A

EPA and DHA

- more double bonds

59
Q

What are produced when fish oil oxidizes and eventually break down into secondary oxidation products?

A

hydroperoxides

60
Q

Steroids inhibit?

A

phospholipases

61
Q

COX-1, COX-2, and aspirin inhibit?

A

cyclooxygenase

62
Q

What will replace arachidonic acid at the sn-2 position of the glycerophospholipids?

A

EPA or DHA

63
Q

EPA inhibits release of arachidonic acid by inhibiting what?

A

phospholipase A2

64
Q

EPA reduces eicosanoids by inhibiting what enzymes?

A

COX and 5-LOX

65
Q

What produces resolvins?

A

EPA and DHA via COX-2, and 5-LOX enzymes

66
Q

Resolvins E1, D1, and neuroprotectin inhibit what?

A
  • IL-1 and TNF

- E-selecctin and ICAM-1 (neutrophil infiltration)

67
Q

NFkB is downregulated by what?

A

EPA and DHA

68
Q

EPA and DHA binds to and activates what transcription factor?

A

PPARy –> inhibits NFkB

69
Q

What supports bone formation at moderate levels but promotes bone resorption at high concentrations?

A

PGE2 –> RANKL receptor of progenitor osteoclasts

70
Q

For what 3 conditions are omega-3 sources most highly recommended?

A
  • hypertriglycerdidemia
  • HTN
  • 2^ CV disease
71
Q

Will supplementation with DHA or EPA increase LDL more?

72
Q

What is the substrate for COX and 5LOX to generate 3-series prostaglandins and 5-series leukotrienes?

73
Q

3-series prostaglandins and 5-series leukotrienes are what, when compared to arachidonic acid?

A

anti-inflammatory

74
Q

What are the precursors for anti-inflam resolvins and neuroprotectin-D1?

A

EPA and DHA

75
Q

EPA/DHA decrease triacylglycerol concentrations by regulating what two nuclear transcription factors?

A
  • Activation of PPAR-alpha

- inactivation of SREBP-1

76
Q

What increases hepatic b-oxidation via activation of lipoprotein lipase?

A

Activation of PPAR-alpha

77
Q

What decreases lipogenesis via reduced production of fatty acid synthase?

A

inactivation of SREBP-1

78
Q

What can prevent calcium overload by inhibiting L-type Ca channels during stress?

A

omega-3’s

79
Q

What can increase Ca/Mg ATPase active transports?

A

omega-3’s

80
Q

What can directly stabilize electrical activity?

81
Q

Which fatty acid is more cardioprotective and why?

A

DHA, because it increases eNOS

82
Q

Which fatty acid reduced coronary events by 19%?

83
Q

Which fatty acid more strongly activated PPAR-alpha?

84
Q

How can omega-3’s be anti-inflammatory?

A

inhibit NF-kB

85
Q

How can omega-3’s be pro-apoptotic?

A

inhibit Bcl-2

86
Q

How can omega-3’s be anti-proliferative?

A

inhibit Ras and TGF-B1

87
Q

How can omega-3’s be anti-angiogenic?

A

inhibit VEGF

88
Q

How can omega-3’s be estrogen antagonistic?

A

down reg of E synthesis or antagonize receptors

89
Q

What serves as a tumor suppressor by activating SDC-1?

90
Q

What is the proteoglycan that inhibits phosphorylation/activation of transcription factors for cell division?

A

syndecan-1 (SDC-1)

91
Q

Which omega-3 has stronger anti-proliferative action?

92
Q

What activates the gene for adipokine adiponectine?

A

PPARy, which is activated by omega-3’s

93
Q

What activates PPAR-alpha and reduces skeletal m. uptake of triacylglycerol?

A

adiponectine

94
Q

What blocks the phosphorylation of IRS and PI3 kinase leading to reduced GLUT 4 translocation?

A

free fatty acids

Nutritional Biochem 2 (6 decks)

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