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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
Why is Energetic Disruption So Problematic?
ROS siphon FADH 2 and NADH from the ETC… and reduces ATP production.
26
cost of ROS
ROS --> Superoxide dismutase --> hydrogen peroxide --> catalase --> water also oxidized into GS-SG To return GS-SG to GSH - needs NADH
27
Causes of Oxidative Stress | 
``` 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
How do heavy metals affect energy production
impair heme biosynthesis --> lower energy
29
e⁻ transport inhibitors: | Complex I
APAP Rotenone, Amytal
30
e⁻ transport inhibitor: | Complex III
Antimycin A
31
e⁻ transport inhibitors: | Complex IV
Cyanide, Carbon Monoxide, Azide
32
ATP synthase Inhibitor: OSCP fraction of ATP synthase –
Oligomycin
33
Uncoupling Agents: Transmembrane H⁺ carrier –
2,4, dinitrophenol, | Pentachlorophenol
34
What effect do organophosphates have on mitochondria?
``` 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
Toxins and mitochondrial dysfunction | organophosphates can cause
``` 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
Mitochondrial P ermeability T ransition P ores MPTP ) reopening what is it?
= ~reperfusion injury
37
MPTP caused by
``` NSAIDS, Acetaminophen, Valproic Acid, Troglitizone, Disulfuram & others ```
38
MPTP Tx
Treatment: Think GLUTATHIONE, it’s precursors and stimulatory regulators... as well as SAMe, TMG, NAC, COQ10
39
Direct Drug inhibition of Beta Oxidation Causes
``` Causes: NSAIDS, Valproic Acid, Amiodarone, Tamoxifen, Acetaminophen ```
40
Direct Drug inhibition of Beta Oxidation Tx
Treatments: Omega 3 oils to stimulate PPARs Butyrate to stimulate peroxisomal b oxidation
41
OxPhos Uncoupling - what is it? induced by?
``` • Normal in Brown Fat • Thermogenin enables creation of heat instead of ATP • Alpha Lipoic Acid induces Brown Fat ```
42
Ox Phos uncoupling causes
``` Ibuprofen, Amiodarone ASA Tamoxifen Diclofenac ```
43
Direct inhibition of the ETC causes
``` Causes: NSAIDS, Amiodarone, Tamoxifen, Diclofenac, Tetracycline, Cyanide, Rotenone, Oligomycin, Anti depressants ```
44
mtDNA depletion or damage causes
Causes: Acetaminophen, Troglitazone, Zidovudine (AZT)
45
When Mitofunctionopenic
• Need less injury from oxidative molecules • Need More & Better Mitochondria
46
How to decrease injury to mito from oxidative stress - genetic hub
NRF 2
47
Genetic hub for mitochondrial biogenesis
PCG 1
48
Genetic hub for mitochondrial biogenesis
PCG 1-alpha
49
best plant/supp for inducing ARE via Nrf2
sulforaphane
50
PGC 1 predominantly expressed in
``` mitochondrial rich tissues - heart skeletal muscle brown adipose tissue liver ```
51
PGC1 α Activators | “Need More Energy Signals”
``` 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
How to increase brown fat
cold exposure
53
PGC 1 α Inhibitors | “Too Many Energy Signals”
``` 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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