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what is the citric acid cycle
is a series of reactions that connects the intermediate acetyl CoA from the catabolic pathways in stage 2, with electron transport and the synthesis of ATP in stage 3
where does the citric acid cycle take place? is it aerobic or anaerobic?
-mitochondria
-aerobic
what does it do with the acetyl CoA
oxidizes the 2 carbons to CO2
what does the citric acid cycle produce
NADH and FADH2 and GTP and CO2
citric acid cycle, aka
krebs cycle
tricarboxylic acid cycle (TCA cycle)
in the citric acid cycle, what occurs with the carbon atoms
6 carbons move through the cycle to produce oxaloacetate (4C) and 2CO2
each cycle of the citric acid cycle produces what?
- 3 NADH
- 1 FADH
-1 GTP which then is directly phosphorylated into ATP
-2 CO2
how many reactions are in the cycle?
8 reactions
what is the purpose of the 8 reactions (overall)
oxidize acetyl CoA from pyruvate or fatty acids, producing CO2 and the high-energy compounds FADH2, NADH, and GTP
what do we need to start the cycle?
acetyl coA and oxalocetate as these combine in the first reaction to form acetate and release 1 CO2
what reactions do we see in citric acid cycle
condensation, dehydration, hydration, oxidation, decarboxylation, reduction, and hydrolysis
in which stage of catabolism does the citric acid cycle occur?
stage 3
in which reactions do we release CO2/ lose C
-reaction 3 when isocitrate is oxidized into alpha-ketoglutarate and loses a carbon
-reaction 4 when alpha-ketoglutarate and CoA are combined to form succinyl CoA
in which reactions do we make NADH
-reaction 3, when we oxidize isocitrate to alpha-ketoglutarate by losing a carbon, NAD+ gains the H
-reaction 4, alpha-ketoglutarate is oxidized by losing CO2 and coA is oxidized by losing H for them to bond and form succinyl CoA, the NAD+ gains the H
-reaction 8, when malate is oxidized to turn an alcohol group into a carbonyl group, the NAD+ gains H
when we lose CO2, what coenzyme is at play
NAD+ —> NADH
In what reaction do we make FADH2
in reaction 6 when succinate gains a c=c bond through oxidation, FAD gains the H’s lost to become FADH2
in what reaction do we make GTP?
in reaction 5 when we turn succinyl coA into succinate removing the coA, which releases energy to make GTP and that makes ATP in the cell
what reactions are oxidation?
reaction 3,4,6,8 (the ones that make NADH or FADH)
what reactions are decarboxylation’s?
reaction 3 and 4
what reaction is involved in direct phosphorylation of ATP
reaction 6- makes GTP
the GTP made in the citric acid makes what
ATP in the cell
what are the intermediate products of the citric acid cycle
1. acetate
2. cis-aconitase —> isocitrate
3. alpha-ketoglutarate
4. succinyl coA
5.succinate
6.fumarate
7.malate
8.oxaloacetate
the citric acid cycle “recycles” what with each cycle
oxaloacetate
when does the citric acid cycle activity increase?
increases when low levels of ATP activate isocitrate dehydrogenase.
when does citric acid cycle reaction rate decrease?
decreases when high levels of ATP or NADH inhibit citrate synthase (first step in cycle).
which reactions act a regulators?
reactions 1,3,4
how is reaction 1 a regulation spot
-high ADP activates citrate synthase
-high NADH, ATP, and citrate inhibit
how is reaction 3 a regulation spot
-isocitrate dehydrogenase is inhibited by high NADH and ATP
-activated by high ADP
how is reaction 4 a regulation spot
-alpha-ketoglutarate dehydrogenase is activated with high ADP
-inhibited by high NADH and succinyl coA
how many cycles of citric acid cycle is involved with 1 glucose
2 because it breaks down to 2 pyruvate—> 2 acetyl coA—> each go in cycle
from 1 glucose so far, what have we made so far (glycolysis, oxdation of pyruvates, citric acid cycle 2 rotation)
- glycolysis: 2 ATP and 2 NADH
- oxidation of 2 pyruvates: 2 NADH
-citric acid cycle for 2 acetyl coa: 6 NADH, 2 FADH2, 2 ATP
total: 4 ATP, 10 NADH, and 2 FADH2
electron transport works with what products made before
coenzymes NADH and FADH from glycolysis, oxidation of pyruvate, and citric acid cycle
what is the purpose of the electron transport chain
a “chain” where hydrogens from NADH and FADH2 are passed from one electron acceptor or carrier to the next until they combine with oxygen to form H2O
what is oxidative phosphorylation
energy released during electron transport is used to synthesize ATP from ADP and Pi
what is the electron transport chain made up of
5 protein complexes (I, II, III, IV, V)
-2 electron carriers, coenzyme Q and cytochrome c, attached to the inner membrane of the mitochondrion, carry electrons among these protein complexes bound to the inner membrane
in electron transport chain, what happens to the coenzymes NADH and FADH2
they are oxidized to NAD+ and FAD by releasing H and electrons
where are the protein complexes located?
in the inner mitocondrial membrane
what protein complexes send H’s into the intermembrane space?
complexes I, III, & IV
what complex is not an integral protein
complex II
what are the 2 electron transported?
coQ and Cyt C
the H ions and electrons given by NADH and FADH2 eventually
react with oxygen to form water
what occurs at complex I
-where electron transfer starts
-1 NADH transfers H ions and electrons to complex 1, in which it oxidizes back to NAD+
-The 4H ions go into the intermembrane space for every 2 electrons that are transfered to CoQ
what happens to CoQ during complex 1
it becomes CoQH2 by getting electrons from complex 1
why do we need a electron transporter
to take the electrons to complex 3 and because it will not undergo oxidative stress
CoQH2 carries electrons from where to where
complex I and II to complex III
how many H go into intermembrane space? for how many electrons
4 H for every 2 electrons passed to CoQ from NADH
what does the pumping of H ions into the intermembrane space cause
a charge separation on opposite sides of membrane
what occurs at complex 2
-complex 2 does go through the inner mitochondrial membrane so does not send H to intermembrane space
-FADH2 gives H’s and electrons to complex 2 which oxidizes it back to FAD
-the Hs and electrons are given to CoQH2
does complex 2 contribute to H+ ion gradient
no because does not pump ions into intermembrane space
CoQH2 does what with the electrons
it gives them to complex 3, which will the have energy to pump H ions into the intermembrane space
complex 3
complex 3 gets electrons from CoQH2 and pumps H’s into intermembrane space
-send electrons to 2 cytochrome C which moves them to complex IV
what is cytochrome C
•contains Fe3+/Fe2+, which is reduced to Fe2+ and oxidized
to Fe3+
-when gets electrons pumps H into intermembrane space
what does cytochrome C do?
transfers electrons between complex III and IV
-generates energy from electron transfer to pump 4H+ from the matrix into the intermembrane space, increasing the hydrogen ion gradient.
what occurs at complex IV
-4 electrons are passed from 4 cytochrome c and are passed to other electron carriers
-the 4 electrons will combine with H ions and oxygen to form water
-energy from this water formation will cause H ions to go into intermembrane space, further increasing H ion gradient
(oxygen is always O2, so 4 electrons and 4 H will produce 2 H20 when combines OR 2H+ with ½ O2 will result in 1 H2O)
chemiosmotic model is for what and does what? (3 things)
oxidative phosphorylation
•links the energy from electron transport to a hydrogen ion gradient that drives the synthesis of ATP.
•allows complexes I, III, and IV to act as hydrogen ion pumps, producing a hydrogen ion gradient.
•equalizes pH and electrical charge between the matrix and intermembrane space that occurs when H+ must return to the matrix.
based on the chemiosmotic model, what happens to the H’s
•H+ cannot move through the inner membrane but returns to the matrix by passing through a fifth protein complex in the inner membrane called ATP synthase (also called complex V).
how do H+ return to the matrix?
returns to the matrix by passing through a fifth protein complex in the inner membrane called ATP synthase (also called complex V).
the flow of H+ from the intermembrane space through the ATP synthase generates energy that is used to
make ATP from ADP and Pi
This process of oxidative phosphorylation:
couples the energy from electron transport to the synthesis of ATP.
for every NADH that is reduced back to NAD+, how much ATP will it produce?
2.5 ATP
for every FADH2 that is reduced back to FAD, how much ATP will it produce?
1.5 ATP
what regulates the electron transport chain and oxidative phosphorylation (4 things)
availability of ADP, Pi, O2, and NADH
when there are decreases in ADP, Pi, oxygen (O2), and NADH, what is the effect on the electron transport chain and oxidative phosphorylation
decreases the formation of ATP due to decreasing electron transport
When a cell is active and ATP is consumed rapidly
the elevated levels of ADP will activate the synthesis of ATP
The activity of electron transport is strongly dependent on the availability of
ADP for ATP synthesis
what is the malate-aspartate shuttle
the way that NADH can enter the mitochondria to deliver the electrons and H+ from glycolysis to the electron transport chain
can NADH enter the mitochondria?
no, only in its oxidized form (NAD+)`
how does the malate aspartate shuttle work
-oxaloacetate is reduced to malate (by malate dehydrogenase) which oxidizes NADH to NAD+
-transporter binds to malate and carries into the mitochondria (across membrane into matrix) bringing the NAD+
-then malate is oxidized back into oxaloacetate by malate dehydrogenase which reduces NAD+ back into NADH (to go to electron transport chain)
-oxaloacetate is then converted to aspartate to leave mitochondria, is converted back into oxaloacetate through deamination, and the process can start again (resulting NAD+ can participate again in glycolysis in the cytosol)
how do we calculate total ATP produced from the oxidation of glucose`
by combining all ATP made at each step
glycolysis
oxidation of pyruvate
citric acid cycle
electron transport chain
in glycolysis how much ATP made (directly and indirectly)
- 2 ATPs made
-2 NADH made —> 5 ATP
TOTAL 7 ATP
in pyruvate oxidation how ATP made (directly and indirectly)
2 NADH made (2 pyruvates into 2 acetyl coA’s)
so 5 ATP made from this
in the citric acid cycle how much ATP made (directly and indirectly)
-2 ATP from GTP ((because glucose—> 2 pyruvate—> 2 acetyl coa—> 2 cycles)
-15 ATP from 6 NADH (because glucose—> 2 pyruvate—> 2 acetyl coa—> 2 cycles)
-3 ATP from 2 FADH2 (because glucose—> 2 pyruvate—> 2 acetyl coa—> 2 cycles)
TOTAL 20 ATP
total ATP from one glucose molecule is
max 32 ATPs
