Z 12. TCA cycle, ET chain and oxidative Phosphorylation Flashcards
what happens to pyruvate when there is sufficient oxygen?
converted to acetyl coenzyme A
what is the role of acetyl coenzyme A?
This molecule links glycolysis (cytoplasm) to Krebs/TCA cycle (matrix of mitochondria)
why can red blood cells only perform glycolysis?
lack mitochondria
TCA
tricarboxylic acid
what is each pyruvic acid converted into?
a 2-carbon acetyl group
what happens to the pyruvic acid molecules?
Remove one molecule of CO2as a waste product
what else does each pyruvate lose?
2 hydrogen atoms
what happens to NAD+?
reduced to NADH + H+
what attaches to coenzyme A?
Acetyl group attached to coenzyme A to form acetyl coA
what is the net gain from glycolysis and link reaction?
2 ATP molecules
4 NADH molecules
2 Acetyl coA molecules
true or false - pyruvate dehydrogenase deficiency is a sex linked disease?
true
what is a cause of pyruvate dehydrogenase deficiency?
build up of lactic acid in the body.
when do symptoms of pyruvate dehydrogenase deficiency appear?
shortly after birth.
what is the most common feature of pyruvate dehydrogenase deficiency?
a potentially life-threatening build up of lactic acid (lactic acidosis),
what can the build up of lactic acid cause?
nausea, vomiting, severe breathing problems, and an abnormal heartbeat
what are some implications of pyruvate dehydrogenase deficiency?
Usually have neurological problems
Most have delayed development of mental abilities and motor skills
why is there lactic acid build up?
When pyruvate cannot be converted to acetyl coA, NAD+ is regenerated from NADH by reduction ofpyruvatetolactate by the enzyme lactatedehydrogenase
why do you think neurological problems occur?
TCA cycle cannot proceed –> energy deficit remains especially in CNS which way cause brain malformation.
what happens after pyruvate has undergone decarboxylation?
it enters the Krebs cycle.
where does the Krebs cycle occur?
matrix of the mitochondria
what does the Krebs cycle consist of?
Consists of a series of redox and decarboxylation reactions
what do the redox reactions do?
transfer energy to NAD+ and FAD
how many ATP molecules are made in the Krebs cycle?
12 ATP molecules (24 per glucose)
what molecules are produced form the Krebs cycle?
3 NADH
1 FADH2
how is the energy from the glucose stored?
the molecules accept the electrons.
what happens with the entry of the acetyl group?
Generates the 6 carbon molecule citrate
what happens to the coenzyme A?
its recycled.
what is the product of the isomeration of citrate?
isocitric acid
what happens in the oxidative decarboxylation?
removal of CO2 & formation of NADH & alpha-ketoglutarate
how is succinyl-coA and NADH formed?
Oxidative decarboxylation and addition of coA
what happens at substrate level phosphorylation?
coA displaced for a phosphate group, which is transferred to GDP and donated to ATP
what is formed at the substrate level phosphorylation?
succinate.
what happens in the dehydration step of the Krebs cycle?
succinate is oxidised to fumarate by FADH2 formation
what happens in the hydration step of the Krebs cycle?
fumarate is converted to malate by addition of water
what is the final step of the Krebs cycle?
Dehydrogenation to oxaloacetate & formation of NADH
How many CO2 molecules does Krebs produce from each glucose molecule?
4
Which enzyme in Krebs allows for substrate level phosphorylation?
Succinyl co-A synthetase
Why do you breathe out more CO2 after exercise?
More turns of Krebs cycle
Which enzymes in Krebs reduce NAD?
Isocitrate, α-ketoglutarate, malate dehydrogenases
How can the TCA cycle be regulated?
Substrate availability
Inhibition by product accumulation
Allosteric inhibition
what is citrate synthase inhibited by?
Inhibited by Citrate & ATP
how is Isocitrate dehydrogenase inhibited?
Inhibited by NADH & ATP
what activates Isocitrate dehydrogenase?
ADP
what inhibits Alpha-ketoglutarate dehydrogenase?
NADH & succinyl CoA
what inhibits pyruvate dehydrogenase?
NADH and acetyl CoA
what other molecules also regulate pyruvate dehydrogenase?
Pyruvate dehydrogenase kinase and phosphatase also regulate the enzyme
what is ATP used for in terms of pyruvate dehydrogenase regulation?
ATP is used to phosphorylate a key Ser residue to inactivate the enzyme
what activates the kinase?
ATP, NADH, acetyl-coA
what inhibits the kinase?
pyruvate.
what are the beginning symptoms of arsenic poisoning?
headaches, confusion, severe diarrhoea, and drowsiness
what symptoms develop as the poisoning develops?
convulsions and changes in fingernail pigmentation
what is the change in fingernail pigmentation due to arsenic poisoning called?
leukonychia striata
what are the symptoms when arsenic poisoning becomes acute?
diarrhoea, vomiting, blood in the urine, cramping muscles, hair loss, stomach pain, and more convulsions
what organs are affected by arsenic poisoning?
lungs, skin, kidneys, and liver
how does arsenic interfere with cellular longevity?
allosteric inhibition of an essential metabolic enzyme pyruvate dehydrogenase (PDH) complex
oxidation of which of the substrates in the citric acid cycle is not coupled to the production of NADH?
succinate
Which of the molecules of TCA cycle is used as a precursor for harm biosynthesis (congenital erythropoietic porphyria)?
Succinyl co A
Which of the molecules of TCA cycle is involved in the formation of Glutamate ?
alpha-ketoglutarate.
Which of the enzymes is involved in this process of formation of GTP from GDP ?
Succinate co-A synthase
Which of the intermediates of TCA cycle can be directly converted to phosphoenolpyruvate to trigger the pathway of gluconeogenesis
Oxaloacetate
what happens as electrons pass through the electron transport chain?
exergonic reactions release energy used to form ATP.
what is the final electron acceptor?
oxygen to form water
what are electron carriers?
integral membrane proteins in the inner mitochondrial membrane.
what happens to NADH dehydrogenase when NADH is oxidised?
it is reduced - redox reaction.
what happens to the carrier proteins as electrons pass through the ETC?
they are oxidised and reduced.
what is oxidation?
loss of electrons
what is reduction?
gain of electrons
why is oxygen important in the process?
without oxygen the redox reaction cannot be repeated.
if the redox reaction doesn’t repeat what happens to the ETC?
it is left saturated.
without oxygen what provides ATP for the ETC?
glycolysis
what is a poison that blocks the ETC?
Cyanide
what is cyanide?
non-competitive inhibitor to cytochrome oxidase.
how does Cyanide work?
blocks the donation of electrons and hydrogen to oxygen, halting aerobic respiration entirely.
what is the benefit of the cristae?
they maximise the surface area of the membrane this increases the rate of ATP production
what is the first protein in the ETC?
NADH dehydrogenase
what does the oxidation off NADH produce?
proton (H+), and NAD+ and 2 electrons
what happens to the electrons produced from the oxidation of NADH?
bind to NADH dehydrogenase.
what happens to the electrons as they move through the ETC?
lose energy
what happens to the energy that is lost?
some is used to pump H+ ions from the matrix into the intermembrane space, the rest is lost as heat.
why does a concentration gradient form?
the inner mitochondrial membrane is impermeable to H+ ions.
how do H+ ions travel into the matrix?
they move down their concentration gradient using protein channels.
what are the protein channels associated with?
enzyme ATP synthase
what does ATP synthase do?
phosphorylates one ADP for each H+ ion that passes through.
what is chemiosmosis?
the use of energy in a chemical gradient to generate ATP by the flow of hydrogen ions through ATP synthase.
what is the final protein in the ETC?
cytochrome oxidase.
what does cytochrome oxidase do?
donates the electron pair to an oxygen atom.
what happens due to the donation of electrons to the oxygen molecules?
releases enough energy to pump other H+ ion across the membrane - can be used to regenerate another molecule of ATP.
what other molecule is also oxidised by the ETC?
FADH2
which protein of the ETC does FADH2 interact with?
the second protein.
what does FADH2 interaction with the second protein mean?
less H+ is pumped into the intermembrane space, so less ATP is regenerated.
what are flavin mononucleotides (FMN)
flavoprotein (protein with a nucleic acid derivative of riboflavin- vitamin B2)
what are cytochromes?
proteins with an iron containing group capable of existing in a reduced (Fe2+) and oxidised (Fe3+) form.
some examples of cytochromes?
cyt b, cyt c1, cyt c, cyt a, cyt a3
what forms the electron transfer centre?
Iron-sulfur centres (Fe-S) contain 2 or 4 iron atoms bound to sulfur atoms
true or false copper atoms participate in the electron transfer?
true - copper atoms bound to 2 proteins participate in the transfer.
what is coenzyme Q?
non-protein carrier in the lipid bilayer
cytochrome c reductase goes through which electron carriers?
Cytochrome b-
Fe-S centre- cytochrome c1 complex
cytochrome oxidase goes through which electron carriers?
Cu -Cyt a – Cyt a3
what happens to the electrons which pass from NADH to NADH reductase?
The electrons are accepted by FMN, and then passed to the iron atoms of the FeS clusters, where Fe3+ changes to Fe2+
what does ubiquinone (coenzyme Q) do?
shuttles the electrons to cytochrome reductase (cytochrome b to FeS centres)
what shuttles the electrons to cytochrome oxidase?
cytochrome c
what happens at cytochrome oxidase?
Cu2+ is converted to Cu+
what is the final electron carrier?
cytochrome c oxidase
what does cytochrome c oxidase do?
passes 4 electrons to molecular oxygen to form 2 molecules of water
how much ATP is generated from each glucose molecule in the electron transfers?
The various electron transfers in the ETC generate either 32 or 34 ATP molecules from each molecule of glucose
how is the ATP generation split between molecules?
Either 28 or 30 from the 10 molecules of NADH + H+ and 2 from each of the 2 molecules of FADH2
what is different about NADH made in glycolysis?
cannot enter the mitochondria
what do the NADH that are made in glycolysis do?
They donate electrons to either the malate or glycerol phosphate shuttle
what organs use the malate shuttle?
liver, kidneys and heart.
how many ATP molecules result from the malate shuttle?
3
what shuttle does the rest of the body use?
glycerol phosphate
how many ATP molecules result from the glycerol phosphate shuttle?
2
what molecule is used as a H acceptor in the glycerol phosphate shuttle?
FAD
how many ATPs are generated from substrate level phosphorylation in glycolysis?
2
how many ATPs are generated from substrate level phosphorylation in the Krebs cycle?
2
what is the first step in the process of NAD+ regeneration in aerobic glycolysis?
NADH from the cytosol gives up its two electrons and Hydrogen to Dihydroxyacetone phosphate (DHAP) forming Glycerol 3-phosphate.
what does glycerol 3-phosphate do?
binds to inner membrane bound glycerol 3-phosphate dehydrogenase (G3PDH)
what does G3PDH have attached to it?
a FAD prosthetic group
where does glycerol 3-phosphate transfer its electrons to?
the FAD prosthetic group.
what is the role of ubiquinone in the regeneration of NAD+?
binds the FAD group, takes the electrons away, shuttling the electrons into the electron transport chain at cytochrome reductase
true or false - cytosolic NADH electrons is equivalent to a mitochondria generated FAD electrons?
true
what happens to glycerol 3-phosphate in the process of giving its electrons to G3PDH?
re-oxidses to forms DHAP - the cycle can begin again.
how many ATPs are produced at the oxidative phosphorylation stage of glycolysis?
4-6
how many ATPs are produced during the link reaction (oxidative phosphorylation)?
6
how many ATPs are produced during the oxidation of succinyl-CoA to succinic acid?
2 GTPs that are converted to ATPs.
how much ATP is produced during the production of 6 NADH + 6H+?
18 ATPs
how much ATP is produced during the production 2 FAD2?
4 ATPs
