Mitochondrial Essentials Flashcards
1.
Recall which organs have the greatest energy use and demands.
Brain
Heart, kidney liver
Why do mito conditions affect bain so much?
Brain Mitos working >5x as hard as Heart Mitos
primary mitochondrial disease
genetic
exacerbated by “minor” triggers
secondary mito disease
size, shape, fission/fusion, movement
in chronic ds - DM, AI, etc.
Mito and PD
dec ETC action (dec ATP)
dysfunctional fission
more ROS
MIto and AD
mito calcium signaling
more fission
ALS and mito
mito defects
Mfr1
does fusion
DLP1
does fission
mito and Breast CA
inc DLP1, dec Mrf2
Sirtuin activation (IV NAD?) - promotes mito fission or fusion?
fusion
•
Melatonin - promotes mito fission or fusion?
fusion
•
Betaine - promotes mito fission or fusion?
fusion
Palmitate- promotes mito fission or fusion?
fission
indomethacin- promotes mito fission or fusion?
fission
S/Sx suggesting mitochondropathy
ptosis ophthamoplegia fatigue diabetes "hypoglycemia
S/Sx suggesting mitochondropathy
ptosis ophthamoplegia deafness fatigue diabetes "hypoglycemia" protein wasting cardiomyopathy cardiac conduction defects WPW tachycardia liver failure
depression migraines headaches weakness dysautonomia fainting neuropathic pain constipation/diarrhea pseudo-obstruction GERD muscle wasting exocrine pancreatic failure (can't make pancreatic enzymes)
CoQ10 level and effect
> 1.7 (or 2)
dec cardiac mortality
Carnitine indications
DM
sepsis
cardiomyopathy
renal ds?
“liver enzymes” and mito/oxid stress
AST and ALT increased to help replete GSH (needs aspartate and alanine)
SAM-e and mito
methylation is dependent on mitochondria! needs ATP
SAM-e and liver cirrhosis
treat early and long-term - decreases liver transplant
SAM-e and NASH
low SAMe leads to low mito GSH –> NASH
what can be used in depression, OA, and HCV?
SAMe
Silymarin = ? and effect and specific application
= milk thistle
protects mitochondria!
helps with chronic liver ds
vit D and mito
helps with better mitochondrial function
improves
Conditions that are examples of intracellular energy deficits.
obesity, CHF, cachexia, diabetes, fatty liver
PGC1-alpha
induces mitochondrial biogenesis
how to make more brown fat?
inducing…
lifestyle
supp/phyto
AMPK
cold
polyphenols
ALA
ALA (alpha lipoic acid) actions
makes more brown fat via AMPK
increases glutathione/anti-ox
metal chelator
ALA effect on met syn
helps with glucose/lipid metabolism, PCOS, TGs
ALA dose and caveat
60 to 2400 mg in divided doses
*extended release to avoid hypoglycemia with higher doses
Low WBC, Neutrophils, and Platelets in mito w/u
•Seen in High Ox Stress States
GGT in mito lab w/u:
Marker of GSH recycling, oxidative stress exposures,
POP accumulation, DMII risk
Mag and mito
needed to activate ATP!
can cause aching, neuro Sx
Ammonia in mito lab w/u
if high, indicates high MTP activity - sign of mito dysfunction and oxid stress
ARGININE!*
L:P ratio in mito w/u
and how to check!
if high, think ETC deficit (or false pos in acute illness)
First Morning Elevated Urine Lactate
plasma AA and mito lab w/u
if global elevation –> catabolism
esp alanine!
acyl-carnitine and mito lab w/u
use in ASD to check for inherited mito ds
CoQ10 uses
hypertension CHF hld depression fatigue athletic performance/recovery Neurodeg AD, PD, HD
CoQ10 uses
hypertension CHF HLD fatigue athletes neurodegeneration AD, PD, HD
Oxidative Stress Markers
DNA - 8OHdg
fats - lipid perox, oxLDL, isoprostane-F2
carb - HbA1C, AGEs
protein- 3 Nitrotyrosine
Others
- Total Antioxidant Capacity (TAC)
- Micronutrient Deficiency serum, RBC, urine
Oxidative Stress Markers in mito lab w/u
DNA - 8OHdg
fats - lipid perox, oxLDL, isoprostane-F2
carb - HbA1C, AGEs
protein- 3 Nitrotyrosine
Others
- Total Antioxidant Capacity (TAC)
- Micronutrient Deficiency serum, RBC, urine
ETC & Citrate Synthase Activity in mito lab w/u
done by muscle biopsy (or buccal swab - experimental)
TRAP1 Gene SNPs
hurt, tired, and queasy chronic pain, fatigue, GI dysmotility "Susan" 1-2% of population in European derived Tx: aggressive anti-oxid
Metabolic Tx for mito diseases
Primary: B vitamins (B1, B2, B3, B5, B6, B12, Folate, Biotin) Iron, Mag CoQ10 Carnitine
Secondary:
Creatine - source of high energy phosphate, buffers ATP, increased exercise/strength but not body comp
AA rebalancing
SAMe
Lipid support Tx for mito ds
Oral:
If fecal fat, GI symptoms, dry skin, consider supporting
Pancreatic Lipase, Bile Acids
Phosphatidyl Choline (PC) - lipid that is part of mito membrane
Fish oil (EPA/DHA)
Flax Oil (aLA)
Evening Primrose Oil/Borage oil (GLA)
Secondary:
IV Lipid Replacement
Oxidative Stress Tx for mito ds
Direct:
Direct Anti oxidants: Vitamin C, Vitamin A, Vitamin E
ALA,
CoQ10
NAC (critical factor for GSH)
Se, Cu, Mn (cofactors for antioxidant enzymes)
Indirect sulforaphane resveratrol curcumin EGCG blueberries
Detox & Inflamm Reduction Interventions for mito ds.
Detox Enzymes etc
- sulforaphane, glucosinolate, quercetin
- silymarin (milk thistle)
- NAC
- TMG choline
- SAM2
Direct glutathione (various methods)
What is Phosphatidyl Choline (PC)
lipid that is part of mito membrane
