Bioenergetics Flashcards
Enzymes that protect body from ROS
Catalase (requires iron)
SOD
Glutathione peroxidase (requires Se)
dietary antioxidant for aqueous compartment
vitamin C
dietary antioxidant for lipid compartment
vitamin E
endogenous antioxidants
glutathione, cysteine, coQ10, lipoic acid, uric acid, cholesterol
Nrf-2 important for…
GSH utilization/production/regeneration
quinone detox
iron sequestration
NADPH production
Phytochemicals that induce Nrf-2
sulforaphane resveratrol quercetin alpha lipoid acid EGCG melatonin
Botanicals that induce Nrf-2
Ginkgo Garlic Cinnamon Coffee Wasabi
S/sxs of mitochondropathy
developmental delays, dementia, Parkinson’s, depression, migraines, HA, weakness, neuropathic pain, muscle wasting, exercise-myalgias, exocrine pancreatic failure, dysmotility, IBS
Mitochondrial function work-up
CBC, ferritin (low iron assoc with mitochondrial dysfunction) CMP, A1c, insulin LFT ammonia lactate lactate: pyruvate ratio creatine kinase quantitative plasma armino acids quantitative urine organic acids plasma acyl-carnitine profile coQ10 ox stress markers, anti-ox capacity
best biomarker for monitoring intracellular ox stress
plasma GSH:GSSG ratio
key findings suggesting mito dysfunction
lactate: pyruvate ratio (low OR high)
low RBC mag
low ferritin
amino acids: elevated alanine, glycine, sarcosine, tyrosine
Mitochondrial dysfunction tx
1. Lifestyle
Sleep, exercise, keto, fasting, cold exposure, Mito Food Plan
Mitochondrial dysfunction tx
2. Metabolic Support
B vitamins Fe, Mg CoQ10 Carnitine creatine monohydrate AA balance SAMe
Mitochondrial dysfunction tx
3. Membrane/lipid support
Support GI absorption of fat
Phosphatidyl choline
EFAs
Phosphatidylethanolamine
Mitochondrial dysfunction tx
4. Ox stress mitigation
all the things
Mitochondrial dysfunction tx
5. Detox interventions
Sulforaphane silymarin NAC TMG SAMe GSH
Functional approach to pain tx
Food first Mito support Healthy fats Improve glycemic/insulin 5 R Gut Stress/lifestyle/self-care Membrane appropriate exercise (??)
Benefit of intermittent fasting/ketogenic diet for mitochondrial dysfunction
increases insulin sensitivity
reduces insulin and leptin
increases mobilizations of FAs
increases BDNF
5 common clinical presentations with mitochondrial dysfunction
Fatigue Headaches Chronic Pain MCI/dementia Depression
how do heavy metals mess with mito function?
interfere with heme production
how do organophosphates mess with mito function?
decreased NADH, succinate cytochrome c reductase, decreased CcOX activity, reduction of mitochondrial membrane potential, decreased ATP, increased ADP/ATP, LDH release, apoptosis
how do organophosphates and organochlorides mess with mito function?
increase ROS damage, increase G6PD activity (impairing glucose metabolism), induce CYP450
Protein that is master regulator of mitochondrial biogenesis and energy homeostasis
PGC-1 alpha
Which organs have greatest energy use and demands?
Brain (1) Muscle (2) Liver Heart Kidney Adipose
Patients with mito dysfunction have s/sxs that are exacerbated by minor trigges such as:
stress, illness, general anesthesia, toxins
S/sxs suggesting mitochondropathy
Ptosis Ophthalmoplegia Kidney wasting Cardiomyopathy Diabetes Hypoglycemia Liver failure Fatigue Depression Migraines/Headaches Neuropathic pain Muscle wasting Exocrine pancreatic failure
Underlying causes of chronic pain
Dysbiosis, IP Microglial activation Inflammation, toxins, meds, LPS Mito dysfunction Neurotransmitter imbalances Excess cortisol, low DHEA Musculoskeletal, TBI, leaky brain
peripheral fatigue
physical capacity and performance ability
measured by gait, strength, endurance
energy depletion - low ATP, depleted by glycogen, reduced pyruvate, malnutrition
metabolic by products - lactate and H due to glycogen breakdown, ammonia due to aa breakdown
dehydration - cardiac output and increased thermal strain
central fatigue
psychic, perceived effort
governed by neural networks, neurotransmitters, emotions, thoughts
measured via TEA - task effort and awareness
Fatigue triggers
travel (infections), ticks, sex (HIV, Hep C), sedentary, poor sleep, EBV, vial, HMB (anemia), DM, thyroid dz, heavy metal toxicity
Labs in neurodegen disorders
Homocysteine, B12, folate A1c, insulin stool test lipids ApoE status
Functional medicine approach to neurodegen disorders
omega 3 and 6 grass fed meat, sprouted legumes 6-9 cups veggies daily (greens, colorful, brassicas/allium/mushrooms) MBSR 5 R low glycemic (avoid dairy based keto) fish oil, esp DHA choline lion's mane
Underlying causes depression
comorbidities - CAD, asthma, AD, PD, HIV, obesity, osteoporosis, DM
poor nutrition
inflammation (mold, infections)
social
ATMs depression
A- FHx, prenatal toxin exposure, genetic SNPs, bonding
T- head injury, trauma, toxin exposure/EDC, abx
M- isolation, substance abuse, pesticides, heavy metals, chronic inflammation, SAD, stress, lack of sun
Functional med approach to depression
zinc, B12, EPA vit D chromium sleep exercise (esp HIIT) gut 5R
