Bioenergetics APM Flashcards
1
Q
What are 5 clinical conditions that may have underlying imbalances in mitochondrial function?
A
Depression Headaches Neurodegeneration Fatigue Centralized pain
2
Q
What are functions of the mitochondria?
A
Buffering calcium ion flux Maintainence of ion gradients Generation of ROS Cell Signaling Growth regulation Biosynthetic pathways ATP synthesis
3
Q
How much ATP do you make daily?
A
Your body weight in kg (on avg 70-80 kg)
4
Q
What percentage of ATP does brain use?
A
22-25%
5
Q
What process do fatty acids go thru to make ATP?
A
Beta oxidation
6
Q
What process do carbohydrates go thru to make ATP?
A
Glycolysis
7
Q
What percent of oxygen does mitochondria consume for oxidative phosphorylation?
A
90%
8
Q
What is the final electron acceptor in the Electron Transport Chain to make ATP?
A
Oxygen
9
Q
What are the 4 distinct parts of the mitochondria?
A
Outer membrane, intermembrane space, inner membrane, matrix
10
Q
Is outer membrane porous or impermeable?
A
porous
11
Q
Is the inner membrane porous or impermeable?
A
impermeable
12
Q
What part of the mitochondria do enzymes involved in mito lipid synthesis sit?
A
Outer membrane
13
Q
What is in the intermembrane space of mitochondria?
A
Hydrogen ions are pumped into here, so low pH
Enzymes that use newly made ATP to phosphorylate sit here, cytochrome C
Calcium ions, ATP
14
Q
What are the cristae in mitochondria made of?
A
Cardiolipin
15
Q
What are in the inner membrane of mitochondria?
A
Cristae
ETC protein complex
ATP synthase
Transport proteins that move molecules into and out of matrix(Ca, Na, HPO4, ATP, ADP, Adenine dinucleotides, etc)
16
Q
What is in the matrix of mitochondria?
A
Kreb cycle enzymes mtDNA ribosomes GSH mtRNA Ca Nitric oxide 1500+proteins of unknown function
17
Q
What are the 2 parts of mitochondrial genome?
A
Genes inside nuclear genome
Genes inside the mitochondria
18
Q
Why are mitochondrial genes not robust?
A
Circular genome Lack histones for protection Highly susceptible to oxidative stress Absent DNA repair 10 x mutation rate - reproduce rapidly
19
Q
Which parent determines your mitochondrial DNA?
A
Mother
20
Q
Which patients may have more mutations in their mitochondrial DNA?
A
Those born to older mothers than younger ones
21
Q
Why are mitochrondia a genotoxic stress sentinel?
A
Damage to and release of mtDNA ellicits a protective signal for cells/tissues to repair their DNA
22
Q
What mediates mito fission?
A
Drp1
23
Q
What is mito fission triggered by?
A
Low GSH/GSSG(low antioxidant potential)
24
Q
What does dysregulated fission lead to?
A
More oxidative stress increased mito depolarization loss of ATP production Reduced insulin stimulated uptake of glucose inability for mitophagy to proceed
25
What happens if dysregulated fission becomes chronic?
leads to low cellular energy state
26
Which enzymes are needed for biosynthesis of mitochondria?
PGC-1alpha, PGC-1beta, TFAM, NRF-1
27
What enzymes participate in mitophagy?
Pink1, Parkin, ATG12, ATG3, Bnip3
28
What enzymes induce fission?
Drp1/Dnm1, DLP-1,
Fis-1, DJ-1
MTFP1
29
What enzymes participate in fused mitochondria?
Mfn1, Mfn2, OMM fusion
30
Mitochondrial dysfunction in what structure has been associated with anxiety and social competitiveness?
nucleus accumbens
31
How do benzo's work?
increase dopamine in nucleus accumbens, regulating mito function by increasing respiration and ATP levels
32
How does mito induce AI disease?
Pore transport induction and small mitoDNA fragments entering the cytosol increase type 1 Interferon production. Type 1 IFN family of innate immune cytokines contributes to AI conditions.
33
Expression of what gene enzyme is master regulator of mitogenesis?
PGC-1alpha
34
Which pathway triggers mitophagy?
PINK1/Parkin pathway - PTEN induced putative kinase 1
35
What promotes mito fission?
```
Meth, cocaine
Etoh, opioids, benzos
Palmitate
Rotenone, pesticides,
Amyloid beta
ischemia
Sedentary
glucose
nsaids
```
36
What promotes mito fusion?
```
Exercise
Fasting/caloric restriction
Cold exposure
Omega 3 PUFAs
Sirtuin activation(IV NAD)
Melatonin
Betaine
```
37
How does beta oxidation work?
Fatty acids add 2 carbon to make acetyl CoA which then enters Krebs cycle
38
How does glycolysis work?
Glucose gets turned into pyruvate which then can bind to acetyl coA and go into kreb cycle
39
What are substrates that drive metabolome?
Fatty acids, amino acids, carbs
40
Is beta oxidation/krebs cycle the only way fatty acids can enter ETC?
No, it can enter directly via complex 3
41
What substances can pyruvate make?
Alcohol, lactate(when no oxygen), glucose, alanine, oxaloacetate which can be made into glucose, Acetyl CoA which can be made back into fatty acids.
42
What is Acetyl CoA made of?
ATP + Pantothenic acid + Acetyl
43
What is central to all acetyl transfers?
B5(Pantothenic acid)
44
What vitamin deficiency will lead to hypoglycemia and why?
B5, impaired insulin receptor downregulation by lack of palmitic acid acetylation of insulin receptor
45
2 AcetylCoA make...?
Beta hydroxy butyrate
46
How many Acetyl CoA can 1 BHB make thru ketooxidation?
2(plus an extra NADH)
47
What is necessary for ETC to make 34 ATP?
Oxygen
48
How much ATP can 1 molecule of palmitate make?
106-129
49
What nutrients are required for fatty acid oxidation?
Carnitine, FAD(riboflavin), NADH(niacin), CoQ10
50
What has more carbon-hydrogen bonds- fats or carbs?
Fatty acids
51
What provides 60-90% of energy for ATP synthesis?
Fatty acid oxidation
52
What happens if not enough carnitine?
You get omega oxidation instead of beta oxidation.
53
What is primary food source for carnitine and what patients may be at higher risk for deficiency?
Meat; vegans/vegetarians
54
What are key nutrients to support mito energy production from Carbs?
B1, B2, B3, B5, Lipoate
55
What are key nutrients to support mito energy production from fats?
Carnitine
56
What are key nutrients to support mito energy production from proteins?
B1, B2, B3, B5, Lipoate
57
What nutrients support the citric acid cycle?
GSH, Fe, Mg, Mn, B1, B2, B3, B5 Lipoate, CoQ10
58
What are key nutrients to support Energy transporters?
Niacin, Riboflavin
59
What are key nutrients to support the ETC?
CoQ10, Vit C, Vit K, Alpha lip acid, Mg, Phosphytidyl Choline
60
Decreases in what substances causes oxidative stress?
Folate, B vitamins, Mineral cofactors, CoQ10, GSH, Carnitine
61
How does NF-KB cause damage?
Increased ox stress leads to increase NF-KB which leads to upregulation of stress/inflammation genes including NOS which leads to RNS, NO, ONO2- which causes cellular damage
62
What is the best marker for monitoring intracellular oxidative stress?
GSH to GSSG ratio
63
How are PUFAs affected by free radicals?
It causes a kink/bend in the bond which disrupts membrane
64
What gets activated by mild-moderate amount of oxidative stress?
NrF2
65
What gets activated by high amount of oxidative stress?
NFkB - inflammation
66
What gets activated by extreme amount of oxidative stress?
AP-1 - Apoptosis
67
How does GPx reduce GSH?
Oxidizes NADPH
68
What inhibits Heme Synthesis pathway?
Heavy metals
69
What protects liver from chemo, arsenic and by how does it regulate mito function?
Metformin: inhibits mito resp chain complex 1, increases intracellular NADH/NAD+ ratio and decreases the intracellular ROS
70
What is the master regulator of mito biogenesis and homeostasis?
PGC-1alpha
71
What are mitochondrial rich tissues?
Skeletal muscle, brown adipose tissue, heart and some extent liver
72
What is effect of exercise on mitochondria?
Increases PGC-1a and Fusion happens more than fission, get better quality/quantity of mitochondria
73
What is effect of sedentary lifestyle on mitochondria?
Decreases PGC-1a which activates NFkB for protein degredation and Fission is greater than fusion so get fragmented and dysfunctional mitochondria
74
What activates PGC-1a?
Exercise, fasting/caloric restriction, cold temp, AMP-Kinase(alpha lipoic acid), Sirt1(activ by NAD), NO, MIto damage, T3
75
What inhibits PGC-1a?
Inactivity, high calorie, saturated fats, refined carbs, fructose, Inflam mediators(TNFa, excessive prooxidants, aging
76
What are top 10 mito therapeutic foods?
```
Salmon
Pomegrante Seeds
Berries
Greens
Green Tea
Olive Oil
Cruciferous veggies
Seaweed
Avocado
Almonds
```
77
Increases in what causes oxidative stress?
```
Oxidative stress,
Nitric oxide
Glucotoxicity
Toxins
Caloric excess
TNF alpha and inflammation
Propionate SCFA
```
78
What enzymes protects the body from ROS?
Catalase(Fe)
Superoxide Dismutase(Zn, Cu, Mn)
GPx(Se) and Glutathione reductase
79
What dietary antioxidants protects the body from ROS?
Vitamin C for aqueous compartments
Vitamin E for lipid compartments
Carotenoids, flavonoids
Albumin
80
What endogenous antioxidants protect the body from ROS?
```
GSH
Cysteine
CoQ10
Lipoic acid
Uric acid
Cholesterol
```
81
What % of plasma does GSH account for?
1%
82
Where does most of GSH reside in?
Intracellular
83
What molecules are central to assembly of the ETC and catalase?
Heme Molecules
84
What are cofactors for the enzymes in the Heme synthesis pathway?
Antiox - lipoic acid
B vitamins - B2, B5, B6, B7
Minerals- Mg, Zn, Cu, Fe
85
Where in the heme biosynthesis does metal inhibition occur?
Pentacarboxyporphyrinogen to coproporphyrinogen via UROD and Coproporphyrinogen to protoporphyrinogen IX visa CPOX
86
What does organophosphate exposure induce?
Decreased NADPH cytochrome C reductase
Decreased succinate cytochrome c reductase
Decreased CcOX activity in mitochondrial respiratory chain
Reduction of mitochondrial transmembrane potential
Decreased ATP production
Increased ADP/ATP ratio
LDH release
Apoptosis/necrotic cell death
Increases ROS damage markers(protein, DNA, fatty acid oxidation)
Alter antioxidant enzyme function(GPx, CAT, SOD, GR)
Increase G6PD activity, impairing glucose metabolism
Induce cytochrome p450 enzymes
87
What is the antioxidant hub?
NRF-2
88
What is the genetic hub?
PGC-1 alpha
89
What are some plants and constituents that induce ARE via NRF2?
```
Sulphoraphane
Curcumin
Ginger
Quercetin, polyphenols
Trans resveratrol
Alpha lipoic acid
Carnosol(rosemary)
Gingko
Garlic
Cinnamon
Green Tea
Milk thistle
Cofee(kahweol and cafestol)
Melatonin
Caffeic acid phenylether ester(CAPE from Bee propolis)
Wasabi
```
90
Food is ....
Medicine
Connection
Information
Energy
91
What primary nutrients activate NRF-2?
```
Cucurmin
Green Tea
Resveratrol
Sulphoraphane
Garlic
DHA
```
92
What processes activate NRF-2?
Fasting
Caloric restriction
Carbohydrate restriction
Mild oxidative stress
93
What is important for the fluidity of mitochondrial membrane?
Fatty acids
94
How do fatty acids regenerate the mito membrane?
Fatty acids conjugate to Carnitine outside the mito, CPT1 transports this across mito membrane
95
What deficiency leads to inability to oxidates fats as fuel?
Carnitine
96
What is the ratio of fat to carbs on a keto diet?
4:1
97
What is mechanism of keto diet?
Unclear but attributed to ketone bodies, glycolysis and mito metabolism
98
What are effects of keto diet?
```
Reduces inflammation
Enhances mito biogenesis
Enhances ATP production
Reduces ROS production
Increases insulin sensitivity
Increases leptin sensitivity
```
99
What are benefits of Intermittent Energy Restriction?
```
Increased insulin sensitivity
Reduced levels of insulin and leptin
Increased mobilization fatty acids
Elevated BHB
Increased BDNF
```
100
What are principles of mito food plan?
```
Phytonutrient density
Low Glycemic
Anti-inflammatory and antioxidant
Fats and oils
Cooking impact
Fasting; Calorie and/or Carb restriction
Organic and clean food
```
101
What are labs to order for mito function?
```
CBC, ferritin
CMP, A1c, Insulin
NH4
Lactate and lactate:pyruvate ratio
CPK
Quan plasma amino acids
Quan urine amino acids
Plasma AcylCarnitine profile
CoQ10
Ox stress markers, Anti ox capacity
ETC and citrate synthase activity testing
genomic/metabolomic evaluation
```
102
What would lab show in lactate/pyruvate to indicate mito dysfunction?
>20 in resp chain d/o
| <10 pyruvate DH defect
103
What would you see on magnesium if mito d/o?
Low RBC Mg
104
What would you see on amino acids if mito defect?
Elevated alanine, proline, glycine, sarcosine, tyrosine
105
What would you see on microscopy to indicate mito dysfunction?
Red ragged fibers
106
What would you see on urinary organic acids if mito defect?
TCA cycle intermediates
Ethylmalonate, Adipate, Suberate
3 methylglutaconate, 3 methylgluterate
Dicarboxylic acids
107
What would you see on acylcarnitine if mito defect?
Low free carnitine
| Elevated acyl:free carnitine ratio
108
How would you tx mito dysfunction?
```
MLF
Metabolic support
Membrane support
Oxidative stress mitigation
Detox interventions and inflammation
```
109
How does exercise affect mitochondria?
Stimulates key stress signals that control skeletal mito biogenesis and function; Increases BDNF, balances BS; Perturbations in mito content and function can directly or indirectly impact skeletal muscle function and whole body health/wellbeing.
110
What are some primary metabolic support for mito?
B vitamins, Fe, Mg, CoQ10, Carnitine
111
What are some secondary metabolic support for mito?
Creatine, BCAA, SAMe
112
What are primary lipid support?
```
If fecal fat, dry skin, GI symptoms - pancreatic lipase, bile acids
PC
Fish oil
Flax Oil
EPO/Borage oil
```
113
What is secondary lipid support?
IV lipids
114
What are some direct ox stress tx?
Vit C, A, E
ALA, CoQ 10
NAC
Se, CU, Mn
115
What are some indirect ox stress tx?
```
Antiox induction agents:
Suphoraphane-Glucosinolate
Resveratrol/Red wine
Curcumin/Tumeric
EGCG/Green Tea
Pterostilbine/Blueberries
```
116
What are detox enzyme inducers/substrates?
Sulphoraphane-Glucosinolate, Quercetin
Milk Thistle
NAC
TMG - Choline rescue to protect PC in membranes
SAMe - supports production of GSH from Hcy
Direct GSH(S-acetyl, liposomal, Intranasal, IV, Nebulized)
117
What is pathophysiology of migraines?
Neuro-biologically based
Vulnerability to migraine - inherited for many
Vascular changes alone do not provide sufficient explanation of pathophysiology
Key pathways for pain are the trigeminovascular input from the meningeal vessels
118
What are common nutrient deficiencies in migraines?
CoQ10, Mg, B6, EPA
119
What is the maladaptive brain response to stress ?
the effects of repeated stress lead to alteration in brain networks both functionally and structurally. As a result brain responds abnormally to environmental conditions.
120
What do you get with oxyphos dysfunction?
Decreased energy
Increased ROS
Altered redox regulation of gene expression and metabolism
Altered calcium homeostasis
121
What are conditionally essential inputs to the metabolome?
```
AA, Arginine
Betaine
Cysteine, Carnitine, CoQ10, Choline
DHA, EPA
GSH, Glycine, Glutamine
Vitamin K2
Lipoic acid
Serine
SAMe
Taurine
Tyrosine
```
122
Oxidation of fatty acids require....
Carnitine
CoQ10
NADH(Niacin)
FAD(riboflavin)
123
What products in urine will you see if you are undergoing omega oxidation?
Adipate
Ethylmalonate
Suberate
124
How much ROS does human produce per year?
1 kg
125
What percent of oxygen is used by mitochondria to make SOD and H2O2?
1-2%
126
Free radicals, ROS and RNS react with and damage ....
Membrane and receptors which impair signaling
Enzymes/other proteins which impairs molecular conversions
Cellular DNA and RNA
Mitochondrial DNA and membranes
127
What are some products of Heme biosynthesis?
Hgb, Myoglobin, Neuroglobin, Cytoglobin, Catalases, Endothelial nitric oxide synthase, TPO, Lactoperoxidase, Eosinophil peroxidase, MPO, CytP450, Cytochromes a,b,c Photsensitive proteins
128
What drugs affect MPTP(mito permeability transition pores? And what is tx?
Nsaids, Acetaminophen, Valproic acid, Troglitizone, Disulfuram;
Tx is GSH(and precursors/regulators - SAMe, TMG, NAC, CoQ10)
129
What drugs cause direct drug inhibition of beta oxidation? and tx?
Nsaids, Valproic Acid, Amiodarone, Tamoxifen, Acetaminophen; Tx: Omega 3 to stimulate PPARs and Butyrate to stimulate peroxisomal b-oxidation
130
What drugs cause oxphos uncoupling? And tx?
Ibuprofen, ASA, Amiodarone, Tamoxifen, diclofenac; Tx - remove cause
131
What drugs inhibit ETC?
Nsaids, Amiodarone, tamoxifen, diclofenac, TCN, cyanide, Rotenone, oligomycin, antidepressants
132
What cause mitodna depletion or damage?
Acetaminophen, Troglitazone, AZT (usually severe, early onset, auto recessive)
133
What is genetic hub for needing less injury from oxidative molecules?
NRF-2
134
What is genetic hub for needing more and better mitochondria?
PGC1-alpha
135
How is NRF-2 an antioxidant hub?
```
Sequesters Iron
GSH utilization/production
Quinone detoxification
Txn production , regeneration and utilization
NADPH production
```
136
What does SOD do?
It makes H2O2 and O2 from free radicals.
137
Where is SOD found in the cell and what cofactors does it need?
Cytosolic(Zn & Cu)
| Mito(Mn)
138
What does Catalase do?
It takes H2O2 made by SOD and converts it to 2 water and O2
139
What does GPx do?
If not enough SOD or CAT, then it will take 2GSH and H2O2 and convert it to 2 H2O and GSSG
140
What is a primary dysfunction in dementia?
Calcium regulation. Impairments in intracellular Calcium handling. Overload promotes superoxides, met dysfunction and cell death.
141
What enymes have altered expression in AD?
DLP1, OPA1, Mfn1, Mfn2 - decreased levels seen
| Fis1 - increased
142
What conditions can be seen with carnitine dysfunctino?
DM, Sepsis, Renal dz, CM
143
What is unique about liver mito?
They are a hub that integrates hepatic metabolism of carbs, lipids, proteins
144
What regulates nuclear and mitochondrial genes?
Estrogen
145
What detoxification pathway is dependent on mito function?
Methylation. If mito dysfunction will be deficient in SAMe as you need ATP to convert methionine to SAMe.
146
How does low SAMe lead to NASH?
Low SAMe -> low GSH -> low PC:PE ratio -> low membrane fluidity -> fat accumulation
147
What supplement reduces liver failure/death or delays transplant in alcoholics?
SAMe but has to be on it for at least 12 months.
148
What supplement is mito protectant in diabetic kidney disease?
Silymarin
149
Why do obese people have less energy despite greater food intake?
Skeletal muscle have smaller mito, reduced contents of mito and impaired electron transport activity
150
What is the mito pathophysiology of IR?
Mito dysfxn(inefficiency of ETC and B ox) -> increased ROS and damaged lipids -> disruptive signaling of insulin pathway -> IR
151
What can you do to induce more white to brown adipose tissue?
cold exposure, polyphenols and alpha lipoic acid; all activate AMPK
152
What are some features of alpha lipoic acid?
Cofactor in decarboxylation of alpha keto acids(pyruvate DH complex)
Blocks stress signaling pathways
Activates AMPK in periphery(brown fat) which activates PGC1-alpha
Activates PPAR gamma which increases insulin sensitivity, dec TGL synthesis
Decreases diabetic complications and DPN
Increases intracellular and mitochondrial GSH
Metal chelator
153
What are findings on CBC with mito dysfxn?
Low hemoglobin, ferritin,
| Low neutrophils, wbc, platelets with high ox stress
154
What is elevated in urea acid or organic acid cycles?
Ammonia
155
What becomes an essential nutrient in Urea acid cycle d/o, organic acid d/o?
Arginine
156
What mitochondrial d/o will you have an elevated L:P ratio?(Lactate to pyruvate)
Inherited d/o of resp chain complex
Tricarboxylic acid cycle d/o
If acutely ill
157
What mito d/o will you have low L:P ratio?
Inherited d/o of pyruvate metabolism
| Defects in the pyruvate DH complex
158
What is not sensitive nor specific marker of mito disease?
Serum lactate. Per Dr. Haase, urinary lactate can be useful for mito dysfxn.
159
What will cause a false positive on organic urinary acids?
MCT oil, fasting
160
What amino acids will be high on Plasma quant aa?
Alanine, proline, glycine, sarcosine, tyrosine
161
What are functions of TCA cycle metabolites?
Signaling molecules regulating chromatin
DNA methylation
Immunity
Hypoxic response
162
What are potential biomarkers for aquired mitochondrial disease in autism d/o?
Unique acyl:carnitine profiles
163
What does elevated acyl:carnitine ratio tell you?
suggests downstream genetic defect
164
What supplement lowers risk of sudden cardiac death?
CoQ10
165
What are some ox stress markers of damaged DNA?
8OHDG
166
What are some ox stress markers of damaged fats?
Lipid peroxidases, oxidized LDL, Isoprostane F2
167
What are some ox stress markers of damaged sugars?
A1c, AGEs
168
What are some ox stress markers of damaged proteins?
3 Nitrotyrosine
169
How to test ETC and Citrate synthase activity?
Muscle biopsy
| Buccal swab
170
What serves as a marker of overall mitochondrial mass?
Citrate Synthase
171
What is Trap1 related disease?
Triad of chronic pain, Gi dysmotility and fatigue due to Trap1 mutation which plays a role in antiox defense. Tx is to tx with antiox
172
How is mood and stress affect associated with mito fxn?
Positive mood is assoc with higher mito health index, negative mood/stress is assoc with lower mito health index
173
Which neurodegenerative d/o should you not use a keto diet in?
ALS
174
What lipids are in the mito membrane?
PC, PS, PE, Phosphatic acid, cardiolipin
175
What is diagnostic criteria for CFS?
```
>= 6 months, not allev by rest and interferes with fxn, no other explanation; at least 4 of the 8:
Post exertional malaise
Impaired concentration or memory
Unrefreshing sleep
HA
Muscle pain
Joint pain
Sore throat
Tender cervical nodes
```
176
What are some lab findings in CFS?
```
Low serum acylcarnitine
muscle bx - abnl mito morphology
decreased GSH, increased lactate in brains of CFS pts
impaired recycling of ADP to ATP
ox damage
```
177
What is peripheral fatigue?
Physical capacity and performance ability. Rises as linear function with exercise and reach a max value only at the point of exercise termination
Mito based
178
How is peripheral fatigue measured?
Gait, strength and endurance testing
179
What conditions is peripheral fatigue higher/lower
Higher - anxiety, depression, neuroticism
| Lower - extroverted personality
180
What improves peripheral fatigue?
Graded exercise
181
What are some characteristics of peripheral fatigue?
1) Energy Depletion: ATP use > production, depletion of muscle glycogen, reduced availability of pyruvate, malnutrition/malabsorption
2) Metabolic by products: lactate and H+ d/t glycogen breakdown, Ammonia d/t aa breakdown
3) Dehydration - affects cardiac output and increased thermal strain
182
What is central fatigue?
Perceived effort. Governed by neural networks, neurotransmitters, neuronal firings, thoughts, beliefs, emotions
A complex emotion
Neurotransmitter based
183
What creates central fatigue?
consciousness producing structures in brain; conscious awareness of changes in the subconscious homeostatic control systems
184
What is blue sclera associated with?
Iron deficiency
185
What organ dz is Dupytrens associated with?
Liver dz
186
What supplement attenuates strength loss and ROM after exericse?
EPA and DHA
187
What cofactor does Tryptophan need to be converted into 5HTP?
Iron
188
What cofactor does 5HTP need to be converted into serotonin?
B6
189
What cofactor does Serotonin need to become melatonin?
SAMe
190
What are neurotransmitters of fatigue?
Trypthophan
Kynuric acid(KYNA)
Quinolate(Quin)
191
When is tryptophan released?
with mental and physical exertion
192
What competes with Tryptophan to enter the brain?
BCAAs
193
What enzyme converts Tryptophan to KYNA?
IDO(indoleamine dioxygenase)
194
What does KYNA covert to?
Quinolate(QUIN)
195
What is an NMDA glutamate channel antagonist?
KYNA
196
What is an NMDA glutamate channel agonist?
QUIN
197
What induces Tryptophan to go thru IDO pathway?
Excess Tryptophan, KYN, steroids, INFgamma, IL1, IL6, TNFalpha, NF-KB
198
What downregulates Tryptophan to go thru the IDO pathway?
E2, NADPH(niacin)
199
What depletes BCAAs?
Exercise
200
How does exercise affect tryptophan?
Exercise depletes BCAAs and releases free fatty acids which displaces tryptophan from albumin so more free tryptophan in blood stream. Both drive up brain tryptophan and central fatigue.
201
What decreases RPE(rate perceived exertion) in exercise?
BCAAs
202
What levels are increased during sleep deprivation?
```
Tryptophan
Serotonin
Taurine
8 acylcarnitines(short and long, not medium)
3 glycerophospholipids
3 sphingolipids
```
203
What is a marker of mitochondrial function imbalance?
8 acylcarnitines(short and long) not medium
204
What are the brain effects of LPS?
Increased glucose utilization in the right more than left insula
Increased glucose utilization in the anterior than posterior insula
Decreased metabolism in anterior cingulate(R>L)
205
What does right insula regulate?
Sympathetic activity so stimulation leads to negative emotions
It receives input from skeletal muscle afferents therefore prevents us from exercising too much.
206
What does anterior cingulate do?
Increases positivity; Inflammation will decrease metabolism in this area. But can be modulated by attention, willpower and intention
207
Is it better to use controlled release 5HTP or immediate release and why?
Controlled to avoid cortisol spike
208
How does interferon alpha cause fatigue?
via IL-6. Inhibits tyrosine hydroxylase conversion to dopamine in BG and decreases CNS homovanilic acid; Decreases THB(B4) by releasing NO - elevated phenylalanine/tyrosine ratio and low BH4 impairs 5HTP as well.
209
How long do you have to instill MLF in neurodegenerative disease before gradually transitioning off meds?
12 months with good effect
210
Why is sleep important for Neurodeg dz?
It helps to clear Tau proteins
211
What can be an early sign of Neurodeg dz?
Sleep disturbance
212
What neurodeg has abnormal REM sleep behavior prior to disease by several years?
Parkinsonism, Dementia
213
What neurodeg has high rates of abnormal sleep/insomnia/osa/circadian rhythm problems, RLS
MS
214
What neurodeg dz has rapid eye movement sleep behavior disorder?
Nonsynucleinopathy neurodeg dz
215
What can be an early effective intervention in neurodeg and psych dz?
Improving sleep
216
How does melatonin affect Alz D?
Improves sleep
Decreases sundowning
Slows progression of cognitive impairment
Protects against amyloid beta toxicity
Decreases amyloid beta production of amyloid fibrils
Serves as a neuro regulator hormone with various mechanisms of actions - free radical scavenger, antiox, antiinflam, immunosuppression
217
What happens to melatonin and cortisol with poor sleep?
Melatonin decreases and cortisol increases
218
Is morning light exposure associated with improved or worsened sleep quality?
Improved
219
Which interleukin is effective for treating both symptoms and pathology of neuroimmune diseases in animal studies? How do you naturally increase this?What inflam markers are decreased?
IL-10 - exercise(studies done with 6 months of exercise) which decreases IL-6 and TNF alpha
220
What is the impact of exercise on the functional and structural changes of the brain?
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Improved connectome
Neuroprotection
Neurogenesis
Oligodendrogenesis
Remyelination
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221
What type of diet led to a better QOL in mild to moderate RRMS patients?
Higher fat, greater intake of micronutrients - cholesterol, folate, iron and magnesium and reduced carbohydrate intake. This led to better ambulation, daily fxn
222
What food intake has a higher correlation with MS?
Liquid cow milk(not cheese). Especially among women if they had high intake during adolescence.
223
What IgG food sensitivities are high in Schizophrenia?
Gluten and Casein
224
What can milk proteins be metabolized into and what is the effect of it?
Morphine like substances called Beta Casomorphin-7 with immune impact
225
What foods are neuroprotective in PD?
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Carotenoids
Caffeine
Fruits
Genistein
Omega 3
Resveratrol
Tea
Veggies
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226
What food is neurodeg in PD?
Milk
227
What are some pros of eggs?
If grass fed - DHA, choline, biotin, lutein, Vit A, D, K2, B3, B6, B9, B12
228
What are cons of eggs?
Most common food allergen in IBD at >70%
60% allergy patients have IgG ab to eggs
13% of those with seasonal allergies have IgG ab to eggs
229
What are most common food triggers to eosinophilic esophagitis?
Milk, wheat, eggs
230
What are 3 sulfur rich foods?
Cabbage(Brassicas), mushrooms, onions(Allium)
231
What components of mushrooms stimulate BDNF and NGF?
Lion's mane(Yamabushitake), hen of the woods and cordyceps stimulate BDNF.
232
How do mushrooms help immunity?
Stimulates natural killer cells; prime innate and adaptive immunity; associated with lower rates of cog decline and depression
233
How do brassicas and alliums help protect against Neuro deg dz?
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Modulate NRF2 pathways
Improve detox
Increase GSH production
Increase Gaba production
Enhance neuroprotection
Improve endothelial function
Fermented sources - beneficial probiotics
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234
What foods are natural ACE inhibitors?
Fermented cabbage(kimchi, sauerkraut) and kefirs
235
Consumption of what foods are associated with less COVID 19 deaths?
Fermented cabbage(kimchi, sauerkraut) and kefirs
236
What probiotic does fermented foods provide?
Lactobacillus
237
Why is vitamin K2 impt for brain?
Myelin protection
Neural stem cells
Calcium influx into bones/teeth
238
Where is K2 produced?
Vitamin K1 is metabolized to K2 in the gut
239
What nutrients to greens have in it?
K2, carotenoids. lutein, zeaxanthin, meso zeaxanthin, folate, Ca, Mg
240
Which pigments are associated with improved cog performance and neuroprotection?
Blue/purple/black polyphenols
241
What food is a good source of CoQ10?
Organ meats
242
What vitamins/minerals/nutrients do organ meats have?
Ubiquinone, EFA, retinol, vitamin A, Vitamin K2-mk4
243
Where is beta carotene converted to vitamin A and by what enzyme?
Intestine, BCMO1
244
What nutrient biomarker patterns were associated with more favorable cognitive and MRI measures?
1) High plasma B1, B2, B6, B9(folate), B12, C, D, E
| 2) High plasma marine n-omega fatty acids
245
How do fatty acids mediate cog fxn?
They modulate neuronal membrane fluidity;. Critical to PFC and visual cortex, Critical factor is ratio of omega 6:3(4:1 is best ratio); helps relapse rate in MS
246
What can predict cognition at age 10?
Levels of EFAs at birth
247
What are beneficial effects of EFAs on MS?
Inflam markers
Glutathione reductase
Reducing relapsing rate
Achieving omega 6:3 balance
248
What are some finding of fat soluble vitamins and MS?
Retinol has inverse relationship with MRI outcomes in RRMS
MS pts had lower K2 blood levels than controls
Relapse risk reduced with Vitamin D at least 20ng
Vit E had inverse relationship with MRI disease activity in RRMS
249
How does stress affect MS?
Increases MS relapse/severity of relapse
Increases risk for AD
Increases freezing of PD and worsening of PD gait
Increases risk of CVD and stroke
250
What is a modifiable risk factor for development of AD?
Smoking
251
What metals are associated with neurodegeneration?
Cd, Cu, Pb, MN, Fe, Methyl Hg
252
What rx drug blocks progenitor cell differentiation inhibiting CNS remyelination?
Simvastatin
253
What synergistic dz with ApoE4 increase risk of AD 5 fold?
DM
254
How does LH/Sex steroid hormone ratio affect neurodeg dz?
Increased ratio drives up TNF alpha and amyloid beta
255
Whats the best way to increase BDNF in PD?
Exercise, mushrooms and fasting/ketosis/metabolic switching
256
What substance can rebuild myelin?
CDP-Choline by increase in oligodendrocyte precursor cells and oligodendrocytes
Upstream approach: Use PC blended with water
