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ifm bioenergetics > The Functional Medicine Approach to Optimizing Energy Production > Flashcards

The Functional Medicine Approach to Optimizing Energy Production Flashcards

1
Q

Recall five common clinical presentations that may have

underlying imbalances in mitochondrial function on the IFM Energy Decision Tree.

A 
Depression
HA
Neurodegeneration
Centralized Pain
Fatigue
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2
Q

Mitochondria and gut

A

Mitochondrial signaling and associated changes in metabolism
impact intestinal homeostasis and regulate intestinal epithelial
cell dedifferentiation.

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3
Q

What promotes mito fusion

A

Sirtuin activation (IV NAD?)
Melatonin
Betaine

Exercise
•
Fasting & Caloric Restriction
•
Cold Exposure
•
w 3 PUFAs
•
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4
Q

What promotes mito fission

A 
ilicit drugs
toxins and pesticides
amyloid‐ β 
Ischemia
NSAIDs (indomethacin)

lack of movement
too much sugar

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5
Q

what makes or burns fat

A

Acetyl Co-A

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6
Q

If no carnitine

A

FA cannot go to B-oxidation –> etc so just get excreted in urine

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7
Q

Pantothenic Acid deficiency can cause

A

HYPOGLYCEMIA
d/t impaired insulin receptor downregulation by lack of acetylation of insulin
receptor.

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8
Q

what is pantothenic acid used for?

A

Central to all acetyl transfers

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9
Q

what does ketogenesis do with Acetyl Co-A?

A

stores two molecules of it

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10
Q

Keto oxidation

A

1.
Ketones are oxidized to create Acetyl CoA.
2.
One beta Hydroxybutyrate produces 2 Acetyl CoA.
3.
Plus an extra NADH!

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11
Q

Why do we focus on fatty acids?
more or less C-H bonds than CHO?
esp important for what organ?

A

More
Make LOTS of ATP
Imp for heart (90% from FA metab)

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12
Q

Oxidation of fatty acids require:

A

Carnitine
FAD (riboflavin)
NADH (niacin)
CoQ10

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13
Q

Key Nutrients to Support

Mitochondrial Energy Production - Carbs

A

B1, B2, B3,B5,

Lipoate

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14
Q

Key Nutrients to Support

Mitochondrial Energy Production - Fats

A

L Carnitine

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15
Q

Key Nutrients to Support

Mitochondrial Energy Production - Proteins

A

B1, B2, B3, B5,

Lipoate

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16
Q

Key Nutrients to Support

Mitochondrial Energy Production - Citric Acid Cycle

A 
Glutathione
Iron
Magnesium
Manganese
B1, B2, B3, B5, Lipoate
CoQ10
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17
Q

Key Nutrients to Support

Mitochondrial Energy Production - Energy Transporters

A

Niacin

Riboflavin

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18
Q

MedicineKey Nutrients to Support

Mitochondrial Energy Production - ETC

A 
Coenzyme Q10
Vitamin C
Vitamin K
Alpha Lipoic acid
Magnesium

Phosphatidyl Choline

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19
Q

Key Nutrients to Support

Mitochondrial Energy Production - Acetyl CoA

A

Pantothenic Acid (B5)

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20
Q

How Does the Body Protect From ROS?

A 
ENZYMES
catalase
superoxide dismutase (req Zn, Cu)
Glutathione peroxidase (req Se)  
glutathione reductase
DIETARY ANTI-OX
Vit C - aqueous
Vit E - lipid compartments
carotenoids
flavonoids
albumin
ENDOGENOUS ANTI-OX
glutathione
cysteine
CoQ10
lipoic acid
uric acid
cholesterol
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21
Q

Enzymes to protect against ROS

A

catalase
superoxide dismutase (req Zn, Cu)
Glutathione peroxidase (req Se)
glutathione reductase

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22
Q

Dietary anti-oxidants to protect against ROS

A

albumin!!

Vit C - aqueous
Vit E - lipid compartments
carotenoids
flavonoids

23
Q

Endogenous anti-oxidant molecules

A 
glutathione
cysteine
CoQ10
lipoic acid
uric acid
cholesterol
24
Q

best marker for monitoring intracellular oxidative stress.

A

Plasma GSH (REDUCED) to GSSG (OXIDIZED) ratio is the

More GS-SG (oxidized) in bloodstream = more oxid stress

25
Q

Why is Energetic Disruption So Problematic?

A

ROS siphon FADH
2 and NADH
from the ETC…
and reduces ATP production.

26
Q

cost of ROS

A

ROS –> Superoxide dismutase –> hydrogen peroxide –> catalase –> water also oxidized into GS-SG
To return GS-SG to GSH - needs NADH

27
Q

Causes of Oxidative Stress

A 
Too much: 
Oxidative Stress
(a feed forward cycle)
Caloric Excess
Nitric Oxide (NO)
SCFA (esp. Propionate)
TNF α & Inflammation
Glucotoxicity
Environmental Toxins (CN+CO
in tobacco; pharmaceuticals,
PCBs, pesticides, toxic metals
Too little: 
Folate & B Vitamins
Mineral Co Factors
CoQ10
Glutathione (GSH)
Carnitine
28
Q

How do heavy metals affect energy production

A

impair heme biosynthesis –> lower energy

29
Q

e⁻ transport inhibitors:

Complex I

A

APAP
Rotenone,
Amytal

30
Q

e⁻ transport inhibitor:

Complex III

A

Antimycin A

31
Q

e⁻ transport inhibitors:

Complex IV

A

Cyanide,
Carbon Monoxide,
Azide

32
Q

ATP synthase Inhibitor:
OSCP fraction of ATP
synthase
–

A

Oligomycin

33
Q

Uncoupling Agents:
Transmembrane H⁺ carrier
–

A

2,4, dinitrophenol,

Pentachlorophenol

34
Q

What effect do organophosphates have on mitochondria?

A 
Oxidative damage
decrease anti-oxid
inc LDH
induce CYP450 
G6PD induction - glucose metab dysf

Affects cytochrome C,
changes membrane potential in mito
decreases ATP
leads to increase LDH and cell death

35
Q

Toxins and mitochondrial dysfunction

organophosphates can cause

A 
Affects cytochrome C, 
changes membrane potential in mito, 
decreases ATP, 
leads to increase LDH and cell death
increase ROS DNA damage 
dec anti-oxidant enzymes
Increase G6PD activity, impairing glucose metabolism
Induce CYP 450 enzymes
36
Q

Mitochondrial P ermeability T ransition P ores
MPTP ) reopening

what is it?

A

= ~reperfusion injury

37
Q

MPTP caused by

A 
NSAIDS, 
Acetaminophen,
Valproic Acid, 
Troglitizone,
Disulfuram & others
38
Q

MPTP Tx

A

Treatment: Think GLUTATHIONE, it’s
precursors and stimulatory regulators…
as well as SAMe, TMG, NAC, COQ10

39
Q

Direct Drug inhibition of Beta Oxidation Causes

A 
Causes: 
NSAIDS,
Valproic Acid,
Amiodarone,
Tamoxifen,
Acetaminophen
40
Q

Direct Drug inhibition of Beta Oxidation Tx

A

Treatments:
Omega 3 oils to stimulate PPARs
Butyrate to stimulate peroxisomal b oxidation

41
Q

OxPhos Uncoupling - what is it?

induced by?

A 
•
Normal in Brown Fat
•
Thermogenin enables creation of heat
instead of ATP
•
Alpha Lipoic Acid induces Brown Fat
42
Q

Ox Phos uncoupling causes

A 
Ibuprofen,
 Amiodarone
ASA
Tamoxifen
Diclofenac
43
Q

Direct inhibition of the ETC causes

A 
Causes:
NSAIDS,
Amiodarone,
Tamoxifen,
Diclofenac,
Tetracycline,
Cyanide,
Rotenone,
Oligomycin,
Anti
depressants
44
Q

mtDNA depletion or damage causes

A

Causes: Acetaminophen, Troglitazone, Zidovudine (AZT)

45
Q

When Mitofunctionopenic

A

•
Need less injury from oxidative molecules

•
Need More & Better Mitochondria

46
Q

How to decrease injury to mito from oxidative stress - genetic hub

A

NRF 2

47
Q

Genetic hub for mitochondrial biogenesis

A

PCG 1

48
Q

Genetic hub for mitochondrial biogenesis

A

PCG 1-alpha

49
Q

best plant/supp for inducing ARE via Nrf2

A

sulforaphane

50
Q

PGC 1 predominantly expressed in

A 
mitochondrial rich tissues - 
heart
skeletal muscle
brown adipose tissue
liver
51
Q

PGC1 α Activators

“Need More Energy Signals”

A 
Exercise (skeletal muscle
Fasting / calorie restriction
cold temp
AMP Kinase (↑AMP/ATP) (alpha lipoic
Sirt1 (deacetylase): activated by NAD
NO
Mitochondrial damage
Triiodothyronine (T3)
52
Q

How to increase brown fat

A

cold exposure

53
Q

PGC 1 α Inhibitors

“Too Many Energy Signals”

A 
inactivity
caloric overload
sat fats
refined carbs
inflamm (e.g. TNF alpha)
too much pro-oxidants
aging

ifm bioenergetics (10 decks)

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