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
CoQ10 intake can spare what vitamin?
vit E
26
What molecule functions as a potent gene regulator?
CoQ10
27
What molecules can be conjugated with glucoronide?
CoQ10
28
Why do CoQ10 levels decrease with age?
1. higher oxidative stress which uses more CoQ10 | 2. reduced enzymatic function
29
What organ is most susceptible to a CoQ10 deficiency?
heart
30
What molecules acts at the mitochondrial level to improve heart function and protect against LDL oxidation?
CoQ10
31
How does CoQ10 reduce BP?
quench free radicals that damage vasodilators such as nitric oxide
32
Both cholesterol and CoQ10 synthesis depend on what enzyme?
HMG-CoA reductase
33
What can block HMG-CoA reductase and lead to decreased CoQ10?
statins
34
What is the most serious statin-induced myopathy?
rhabdomyolysis
35
Supplementing with which molecule is recommended to prevent myopathic side effects from statin drugs?
CoQ10
36
What are the 3 forms of omega-3 fatty acids?
ALA, EPA, DHA
37
What are the conditionally essential fatty acids?
EPA and DHA
38
ALA is synthesized by?
plants
39
DHA concentrations are highest where?
retina and cerebral cortex | - EPA is low in all tissues
40
ALA is converted to EPA and DHA in?
SER
41
Final B-oxidation of ALA occurs where?
peroxisome
42
Linoleic acid goes to y-linolenic acid by what enzyme?
fatty acid desaturase 2
43
Linoleic acid goes to y-linolenic acid by what enzyme?
^6 desaturase
44
di-homo-y-linolenic acid goes to arachidonic acid by what enzyme?
^5 desaturase
45
What is the rate limiting step in ALA conversion?
fatty acid desaturase 2 | - decreases with age
46
What is the rate limiting step in ALA conversion?
^6 desaturase | - decreases with age
47
What is the most rapidly oxidized unsaturated FA?
ALA
48
What is the most rapidly oxidized unsaturated FA?
ALA
49
What competes with ALA for access to ^6 desaturase?
LA
50
Stearidonic acid elevates?
EPA, but not DHA
51
What inhibits ^6 and ^5 desaturase and therefore reduces EPA and DHA?
alcohol
52
DHA supp raises what?
EPA | retro-conversion
53
What found in fish is neurotoxic?
methylmercury
54
Why do fish oil supp's contain less mercury than fish?
1. smaller fish are used 2. mercury binds to protein 3. distilling
55
Farmed fish have lower mervury than wild but higher what?
dioxins, PCB, and chlordane
56
There is a larger omega-3 to toxin ratio in farm or fresh fish?
farm
57
Markers for oxidative stress and redox balance, such as MDA, reduced vit C and E, and elevated catalase and glutathione peroxidase are affected by?
Oxidized lipids
58
Which omega-3 are more suseptible to lipid oxidation?
EPA and DHA | - more double bonds
59
What are produced when fish oil oxidizes and eventually break down into secondary oxidation products?
hydroperoxides
60
Steroids inhibit?
phospholipases
61
COX-1, COX-2, and aspirin inhibit?
cyclooxygenase
62
What will replace arachidonic acid at the sn-2 position of the glycerophospholipids?
EPA or DHA
63
EPA inhibits release of arachidonic acid by inhibiting what?
phospholipase A2
64
EPA reduces eicosanoids by inhibiting what enzymes?
COX and 5-LOX
65
What produces resolvins?
EPA and DHA via COX-2, and 5-LOX enzymes
66
Resolvins E1, D1, and neuroprotectin inhibit what?
- IL-1 and TNF | - E-selecctin and ICAM-1 (neutrophil infiltration)
67
NFkB is downregulated by what?
EPA and DHA
68
EPA and DHA binds to and activates what transcription factor?
PPARy --> inhibits NFkB
69
What supports bone formation at moderate levels but promotes bone resorption at high concentrations?
PGE2 --> RANKL receptor of progenitor osteoclasts
70
For what 3 conditions are omega-3 sources most highly recommended?
- hypertriglycerdidemia - HTN - 2^ CV disease
71
Will supplementation with DHA or EPA increase LDL more?
DHA
72
What is the substrate for COX and 5LOX to generate 3-series prostaglandins and 5-series leukotrienes?
EPA
73
3-series prostaglandins and 5-series leukotrienes are what, when compared to arachidonic acid?
anti-inflammatory
74
What are the precursors for anti-inflam resolvins and neuroprotectin-D1?
EPA and DHA
75
EPA/DHA decrease triacylglycerol concentrations by regulating what two nuclear transcription factors?
- Activation of PPAR-alpha | - inactivation of SREBP-1
76
What increases hepatic b-oxidation via activation of lipoprotein lipase?
Activation of PPAR-alpha
77
What decreases lipogenesis via reduced production of fatty acid synthase?
inactivation of SREBP-1
78
What can prevent calcium overload by inhibiting L-type Ca channels during stress?
omega-3's
79
What can increase Ca/Mg ATPase active transports?
omega-3's
80
What can directly stabilize electrical activity?
EPA
81
Which fatty acid is more cardioprotective and why?
DHA, because it increases eNOS
82
Which fatty acid reduced coronary events by 19%?
EPA
83
Which fatty acid more strongly activated PPAR-alpha?
EPA
84
How can omega-3's be anti-inflammatory?
inhibit NF-kB
85
How can omega-3's be pro-apoptotic?
inhibit Bcl-2
86
How can omega-3's be anti-proliferative?
inhibit Ras and TGF-B1
87
How can omega-3's be anti-angiogenic?
inhibit VEGF
88
How can omega-3's be estrogen antagonistic?
down reg of E synthesis or antagonize receptors
89
What serves as a tumor suppressor by activating SDC-1?
PPAR-y
90
What is the proteoglycan that inhibits phosphorylation/activation of transcription factors for cell division?
syndecan-1 (SDC-1)
91
Which omega-3 has stronger anti-proliferative action?
EPA
92
What activates the gene for adipokine adiponectine?
PPARy, which is activated by omega-3's
93
What activates PPAR-alpha and reduces skeletal m. uptake of triacylglycerol?
adiponectine
94
What blocks the phosphorylation of IRS and PI3 kinase leading to reduced GLUT 4 translocation?
free fatty acids