EXAM3_L31_TCA_ETC_OXPHOS Flashcards
What are the 5 coenzymes of PDHC?
TFNCL (thursday,friday, night comes laughter)
Tpp-B1- Thiamine Fad-B2- riboflavin Nad-B3- niacin Coa-B5- PAN TO THE NATE (pantothenate) LipoicAcid
What products come from 1 acetyl CoA?
3 NADH
2 CO2
1 FADH2
1 GTP
What happens to TCA if no oxygen?
Buildup of NADH, FADH2 (b/c decreased ETC)
buildup NADH will inhibit TCA (PDHC)
Glucose cannot be formed (de novo) by using what from the TCA?
Glucose can’t be made from Acetyl CoA from TCA
All regulatory enzymes in TCA are located in the Mitochondrial matrix except?
Succinate Dehydrogenase (inner mitochondrial membrane) - part of Complex II of ETC
What are the 4 Regulatory Enzymes of TCA?
Which one is rate limiting enzyme?
- Citrate Synthase
- ICDH* (rate limiting)
- a-KGDHC
- Succinyl CoA Synthesis (SS)
The rate limiting enzyme ICDH is activated and inhibited by?
Activated by ADP
Inhibited by NADH and ATP
What TCA enzyme requires the same 5 coenzymes as PDHC?
Alpha ketogluterate dehydrogenase
TFNCL
ADP : ATP ratio is fixed so if you have too much ADP?
What does ADP activate?
you don’t have enough ATP
ADP activates ICDH
TCA Cycle is NOT regulated by Insulin, Glucagon, Epinephrine and is ALWAYS ON, so what regulates it?
energy levels of (ATP, NADH, ADP)
and [intermediates] mainly OAA levels
Where is OAA derived? What enzyme required?
Pyruvate is converted to OAA by pyruvate carboxylase
How is TCA primed?
Pyruvate is converted to OAA by pyruvate carboxylase to start the cycle
What are the levels of NADH and ATP in the Fasted State?
High NADH and HIGH ATP (beta oxidation used)
- TCA inhibited and slows down
Where does NADH and ATP come from when fasting?
Why is TCA inhibited during fasting?
Beta oxidation makes NADH & FADH2 > ATP
the High levels of NADH inhibit the TCA
When citrate accumulates in TCA (fed state) what happens to it?
Exported to cytosol via Citrate Shuttle to deliver Acetyl-CoA
FATTY ACID SYNTHESIS then occurs
(acetyl coa can’t exit tca by itself, has to be in citrate form)
What TCA intermediate used for heme synthesis?
Succinyl-CoA
OAA can’t exit TCA into cytosol (fasted state) by itself so it uses what shuttle to get into cytosol?
What is it then used for?
Malate Shuttle to be used in gluconeogenesis
-malate carries OAA to the cytosol in the fasted state
What three areas is Thiamine essential for?
- PDHC
- alpha-KGDH (TCA)
- branch chain ketoacid dehydrogenase (muscle/brian energy)
What is beri-beri?
Thiamine (Vit B1) deficiency “weak! weak!”
Impairs: PDHC,aKGDH, bcaKADH
What pathology of beri beri?
Nervous (strange eye movement)
Cardiac (heart failure)
if thiamine deficient
Arsenic Poisoning: ARSENITE (trivalent)
Inhibits LIPOIC ACID: Decreased ATP Production:
Affects: PDHC, aKGDH, bcaKADH
Arsenic Poisoning: ARESENATE (pentavalent)
Inhibits step 6 glycolysis
Decreased NADH and ATP production
What is pathology of ARSENATE (pentavalent)
MEES’ Lines on nails
Nerve damage, Skin hyperkeratosis, cancer risk,
4 sources of NADH?
- aerobic glycolysis (malate shuttle)
- PDHC
- TCA
- Beta Oxidation
3 sources of FADH2?
- Aerobic glycolysis (glycerol phosphate shuttle)
- TCA (succinate dehydrogenase)
- Beta Oxidation
4 complexes of ETC?
Ndh(Sdh,g3p)CbcCaa3
(NFQCO) : N>F,F>Q,Q>C,C>O
1- NADdh- NADH to FMN
2- succinate-dh and glycerol-3p shuttle (FADH2 to CoQ)
3-cytochrome b/c1 (CoQ to Cytochrome C)
4-cytochrome a/a3 (cytochrome C to oxygen)
3 Inhibitors/poisons of ETC
- Cyanide (complex IV)
- CO (complex IV)
- Barbiturates (complex II)
Antidote for Cyanide poisoning?
NITRITES- convert Hb (Fe2+) to metHb (Fe3+)
oxygen
CO Poisoning
CO binds Hb displacing oxygen
OXYGEN TREATMENT
headache, nausea, tachycardia, tachypnea
red lips and cheeks,
respiratory depression, coma, death
Uncouplers
ruin proton gradient but electron transfer is ok.
-Decreased ATP synthesis
-body compensates by trying to make more NADH and consumes more oxygen
_ENERGY RELEASED AS HEAT (b/c no atp synth)
Natural uncoupler proteins (UCP: THERMOGENIN)
Found in brown fat of infants to keep them warm
Why is brown fat brown?
High concentration of pigments in mitochondria from Cytochromes
Hyperthyroidism and mitochondrial uncoupling
hyperthyroid can increase mitochondrial uncoupling
- TH may alter IMM
- TH may increase complex IV synthesis
What is TCA and OP regulated by?
Oxygen and ADP mainly
decreased o2> decreased OP (increases NADH FADH2)
TCA inhibited via ICDH (respiratory control)
Decreased oxygen has what affect on Oxphos
decreases OP but increases NADH FADH2 Inhibits TCA (known as respiratory control)
When oxygen sufficient for Oxphos, then ADP regulates it.
high/low adp?
High ADP means low ATP
so - ADP activates TCA via ICDH to make more
