Mitochondrial Disorders Pt. 1 Flashcards
Define “metabolism”
How the body (all organs, all cells) functions by generating energy through intricate chemical steps from daily nutrition/food consumption.
Define “basal metabolic rate”
Minimum calories needed at rest for energy for overall cell/organ function. This includes functions such as:
- Ion transport
- Digestion
- Brain activity
- Gut movement
- Breathing
- Heart pumping
Percent of Basal Metabolic Rate: Muscle (20%), Liver (19%), Brain (17%), Digestion (10%), Heart (8%), Kidneys (7%), Fat (3%), rest is misc.
Name some things that impact your overall metabolic rate
Resting metabolic rate: warmth regulation, digestion, other processes
Daily activity: physical, mental
Demographics: gender, age, physique
What are the 4 components of food?
Fat, Carbs, Protein, Vitamins
What is the function of a vitamin?
Cofactor for crucial metabolic pathways
What is the normal pH that is essential for proper functions of all enzymes in the body?
7.4
Name a change from the norm (homeostasis) that can be life threatening
Acidosis (particularly lactic acidosis)
What is it called when protein breakdown happens during illness?
Catabolism
What is the main energy source for your cells?
Glucose
Blood glucose needs to be between ___ - ___ mg/dL for adequate function of organs (including the brain)
80-120 mg/dL
___ is how extra glucose is stored and also what is converted back into glucose when needed
Glycogen
Where are fatty acids absorbed?
Gut
Where are fatty acids processed?
Liver
where does energy metabolism occur?
Mitochondria
What are stored for energy once glucose/glycogen stores are depleted?
Fatty Acids
Fatty Acids are the main source of energy for what?
Muscle, including the heart
Enzyme defects can be partial or complete. What determines the severity and onset of illness?
Residual or remaining enzyme activity
- Mild –> teenage/adult presentation
- Severe –> newborn
What might you need to measure enzyme activity, since direct can be difficult?
Tissue Biopsy
What does Mitochondrial Dysfunction result in?
Cell injury –> cell death –> organ failure
What organs are most impacted by mitochondrial dysfunction?
Organs w/ high energy demand
- Muscle (cardiac and skeletal)
- Endocrine organs
- Kidneys
- Intestinal tract
- Retina
- CNS
Define “mitochondrial disease”
Chronic disorders that occur when mitochondria in numerous cells fail to produce sufficient energy for adequate function w/ subsequent organ failure
Mito diseases are the result of either ___ or ___ mutations in ___ or ___
inherited, spontaneous, mtDNA, nDNA
Note: these mutations lead to altered function of proteins or RNA inside the mitochondria
Name 6 other major metabolic pathways that mitochondria are involved in
- Purine/pyrimidine biosynthesis
- Heme synthesis
- Urea cycle
- Cholesterol metabolism/hormone synthesis
- Neurotransmitter metabolism
- Free radical production and detoxification
What are mitochondria prone to?
Environmental insults such as aging, drugs, etc.
What is meant by “mitochondria are dynamic organelles”?
They divide, fuse, and migrate
True or false: a single cell can contain both mutant/defective mitochondria and normal mitochondria
True
Note: this is why symptoms can be so variable b/w individuals in the same family. Ratios can also change over time and as we age, we all get mitochondrial damage
What 6 things occur in cells w/ defective mitochondria?
- No ATP
- Backlog of unused fuel molecules and oxygen (free radicals toxic to cell)
- Inadequate oxygen supply
- Lactic acidosis damages muscle and nerve tissue
- Reactive oxygen species
- Vitamins/antioxidants target this issue to minimize tissue damage
What is the ONLY way we can measure activity of the electron chain complexes (in the oxidative phosphorylation process/respiratory chain)?
Must use fresh or frozen muscle biopsy, fresh is optimal for evaluation
Note: only a few labs still do this testing since it’s mostly been replaces by genetic testing
How many genes does it take to make a mitochondrion?
3000
What is the only metabolic pathway under dual control of both the mtDNA and nDNA genomes?
Electron transport chain
Regarding the genes that control the electron transport chain:
nDNA has ___ genes and has ___ inheritance pattern
vs.
mtDNA has ___ genes and has ___ inheritance pattern
850 genes, AR
vs.
13 genes, Mitochondrial inheritance through maternal circular DNA
Describe mtDNA
- closed, circular
- maternally inherited
- thousands of copies per cell
- copy number is very dynamic
What are 3 concepts that impact the effect of a mitochondrial disease on a person?
- Heteroplasmy: presence of mixture of mutant and normal mtDNAs
- Tissue distribution: which tissues have the mutant mtDNAs
- Threshold effect: vulnerability of each tissue to impaired oxidative metabolism
Note: at cell division, mitochondria are distributed unequally and do not necessarily reflect the ratio found in the progenitor cell
