Mito Flashcards
What is your basal metabolic rate?
minimum # of calories needed at rest for energy for overall cell/organ function
What tissues require the most of our BMR?
Organs (brain, liver, heart, kidneys) - 58%
Skeletal muscle (22%)
Why are vitamine necessary?
function as cofactors that are necessary for pathways
If your pH drops below 7.2 you are in:
acidosis
If your pH rises above 7.5 you are in:
alkalosis
What macromolecule are neurotransmitters made from?
amino acids
What level should our blood glucose be at for adequate organ fxn?
80-120mg/dl
Fatty acids are the main source of energy for what organs?
muscle and heart
What’s the most effective way to measure enzyme activity?
tissue biopsy
Mitochondrial conditions result from mutations in what genes?
mtDNA or nDNA
Defects in the Krebs cycle are often caused by? Fatty acids? respiratory chain?
AR nDNA
nDNA
mtDNA from mom and AR conditions
What are some other functions of mitochondria?
DNA synthesis Heme synthesis Urea cycle hormone synthesis neurotransmitter metabolism free radical production and detox
What happens in cells with defective mitochondria?
- no ATP
- severe impact of other mito fxn
- free radicals accumulate
- lactic acidosis
How many oxidative phosphorylation complexes exist? What genes code for them? How can we measure their activity?
5
mtDNA and nDNA
fresh or frozen muscle biopsy
How many nDNA genes do we have? mtDNA?
850 nDNA vs. 13 mtDNA
How do nDNA mutations result in disease (this came from our lecture but I don’t like it now that I see it again)?
autosomal recessive inheritance
What is unique about mtDNA?
- closed, circular DNA
- maternally inherited
- thousands of copies per cell
- copy number is dynamic
3243A>G in mtDNA accounts for 90% of what condition?
MELAS
What are three factors we should consider with mito conditions?
heteroplasmy
tissue distribution
threshold effect (vulnerability of each tissue to impaired oxidative metabolism)
how common are mitochondrial diseases?
1:4,000 in children in US by age 10
Mitochondrial diseases are typically _______ and _________.
progressive and mutlisystemic
What types of organs are most impacted by mito conditions? ex?
those with high energy demand
skeletal and cardiac muscle, endocrine organs, kidney, motility in intestinal tract, retina, central nervous system
when might we suspect a mito condition?
seeing involvement of 3 or more organ systems without a unifying dx
What are some of the neurologic red flags for mito conditions?
- stroke-like lesions in non-vascular patterns
- basal ganglia disease
- encephalopathy
- intractable epilepsy
- myoclonus (esp. in children)
- ataxia
- MRI findings consistent with Leigh
- MRS peaks
What are some of the cardio red flags for mito conditions?
- hypertrophic cardiomyopathy with rhythm disturbance
- unexplained heart block in child
- cardiomyopathy with lactic acidosis
- dilated cardiomyopathy with muscle weakness
- Wolff-Parkinson-White arrhythmia
What are some of the ophthalmologic red flags for mito conditions?
-retinal degenration with signs of night blindness, color-vision deficits, decreased visual acuity, or pigmentary retinopathy
-not able to move eyes
-roving eyes
-ptosis (droopy eyelids)
sudden blindness
What are some of the GI red flags for mito conditions?
- unexplained or valproate liver-failure
- severe dysmotility
- pseudo-obstructive episodes
What are some other red flags for mito conditions?
- newborn, infant, or young child wit unexplained hypotonia, weakness, FTT, and metabolic acidosis (particularly lactic)
- exercise intolerance not proportionate to weakness
- hypersensitivity to general anesthesia
- episodes of acute rhabdomyolysis
- fibromyalgia in young people
What are the most common expression of enchephalomyopathy in mito conditions?
hearing impairment, migraine-like headaches, and seizures
does a normal lactate rule out mitochondrial disorders?
no - lactate may only rise during episodes
Leigh, Kearns-Sayre syndrome, Leber, and others frequently occur with little or no lactate elevation
What deos MELAS stand for?
When does MELAS typically present? Features? Main mutation?
MItochondrial Encephalopathy-Lactic Acidsosis-Stroke-Like episodes
- childhood to early adulthood
- recurrent strokes that manifest as migraine-like headaches, vomiting and (less often) seizures, and can cause permanent brain damage
- can occur in infancy with DD and LD before first stroke
mutation: m.3243A>G (>80%)
How can we treat MELAS?
Arginine may have some protective benefit
When does KSS present? Its features?
- <20y
- progressive external ophthalmoplegia (initail) and pigmentary retinopathy, salt-and-pepper pigmentation in retina, conduction block in heart, ataxia
What mutation(s) often cause KSS?
deletions of mtDNA
common one is m.8470_13446del4977
When does Pearson syndrome present? Features?
If these individuals survive they often develop:
infancy
severe anemia and malfunction of pancreas
KSS
When doe Leigh syndrome present? Features? Leads to?
infancy
brain abn that may result in ataxia, seizures, impaired vision and hearing, DD and altered control over breathing
causes muscle weakness (swallowing, speech, and eye movement)
poor outcome
This condition presents in infancy with muscle weakness and/or liver failure and possibly brain abn.
MDS
This condition presents in late childhood to adolescence with myoclonus, seizures, ataxia and muscle weakness. It also can cause hearing impairment and short stature.
MERRF (myoclonus epilepsy with ragged red fibers)
This condition presents typically <20y with PEO, ptosis, limb weakness and GI problems (dhronic diarrhea and abdominal pain) and peripheral neuorpathy.
MNGIE
This condition presents in infancy to adulthood with neuropathy, ataxia, and retinitis pigmentosa. Perhaps DD, seizures, and dementia
NARP
