Part 2.3 Flashcards
a-ketoglutarate AA precursors
Arginine, ornithine, proline, histidine, glutamine –> Glutamate –> a-ketoglutarate
Acetyl-coa precursor AA
Alanine, tryptophan, methionine/cysteine, glycine, serine, threonine
Oxaloacetate precursor AA
Asparagine and aspartate
Fumarate precursor AA
Asparagine and phenylalanine/tyrosine
Pyruvate precursor AA
phenylalanine/tyrosine, tryptophan, isoleucine/leucine/lysine
Succinyl-coA precursor AA
Valine, isoleucine, methionine, threonine (propionate)
Krebs cycle pathways for gluconeogenesis and lipogenesis
Krebs precursor for heme synthesis and urea cycle
Gluconeogenesis: Oxaloacetate –> Malate (exits mitochondria) –> Oxaloacetate –> Phosphoenolpyruvate (PEP) ———-> Glucose
Lipogenesis: citrate –> acetyl coA ———-> FA/isoprenoids
Succinyl-CoA necessary for heme synthesis
Fumarate required for the urea cycle
oxaloacetate pathway for AA synthesis
a-ketoglutarate pathway for AA synthesis
Oxaloacetate –> Aspartate –> asparagine
a-ketoglutarate –> glutamate –> glutamine, proline, arginine
Acetyl coA as a metabolic intermediate
glucose, fatty acids, and some amino acids (Alanine, tryptophan, methionine/cysteine, glycine, serine, threonine) feed into it
Nutrients required for the ETC
Complex I: FMN (riboflavin) and Fe-S
Complex II: Fe-S
Complex III: 2 heme (Cytb, Cyt-c1) and Fe-S (so 3 Fe total)
- Cytochrome c (heme)
Complex IV: Cu, Heme (Cyt-a and Cyt-a3)
CoQ 10 oxidized and reduced forms
Ubiquinone (oxidized) –> Ubiquinol (reduced)
Carries e- from complex I/II to complex III
Cells can synthesize coQ10 but people who take statins must supplement
How is cholesterogenesis diverted to make coQ10?
Effect of statins?
Supplementation
Cholesterogenesis pathway intermediates can be diverted to produce CoQ10 :
Acetyl-coA –> acetoacetyl coA –> HMG-coA –> mevalonate –> coQ10
statins inhibit HMG-coA reductase so no mevalonate is produced, blocking coQ10 production
Mitochondria targeted coQ10 (MitoQ) is tagged with TPP (thiamine pyrophosphate) used to ensure entry into mitochondria for supplementation
How thermogenin and other respiration uncoupling methods work
Thermogenin or Uncoupling Protein-1 (UCP-1) - inhibits ATP synthase and acts as a channel to transport H+ into the mitochondrial matrix
- this release of proton motive force energy is released as heat
- triggered by fatty acid catalysis from brown adipose
Asprin uncouples respiration by carrying protons across the membrane (warming up side effect)
DNP dinitrophenol - proton carrier as well
- People exposed to DNP experienced weight loss due to increased energy expenditure (but can be lethal in higher doses)
O2 saturation as a measure of mitochondrial efficiency
Sex dimorphisms in mitochondrial respiration
1) Add mitochondria and get baseline of respiration
2) Add substrate and measure O2 dip
3) Add ADP which increases rate of respiration (works through complex V)
4) Add oligomycin which is an inhibitor for complex 5, inhibiting respiration
5) FCCP added or another proton carrier
6) antimycin A added to completely inhibit ETC
Liver and muscle mitochondria respire better in women than in men
Diet sensitive individuals
Reduced UCP-3 expression in obese, diet-resistant women
Diet sensitive individuals have mitochondria that respire better
Parts of the Krebs cycle where AA can feed in
Pyruvate, acetyl coA, oxaloacetate, a-ketoglutarate, succinyl-coA and fumarate
