Citric acid cycle and electron transport chain Flashcards
Pathways that metabolize carbohydrates
Glycolysis Glucoenogenesis Glycogenesis Glycogenolysis PPP
Pathways for protein metabolism
Transamination Urea cycle AA catabolism AA synthesis Synthesis of AA derivatives
Pathways for synthesis of fat metabolism
Beta-oxidation
FA synthesis
TG synthesis
Cholesterol synthesis
Nucleic acids require precursors from what food groups
From carbohydrates and proteins
How can we get acetyl-CoA
Beta-oxidation
Some AA (leucine, threonine,etc.)
Pyruvate
Conversion of pyruvate to acetyl-CoA ( what enzymes , what products)
Pyruvate dehydrogenase complex(PDC) (3 enzymes) uses CoA-SH and NAD+ to convert pyruvate to acetyl-CoA
Products: CO2, NADH
What type of reaction is the conversion of pyruvate to Acetyl-CoA
Oxidative decarboxylation
Irreversible
Each cluster of PDC has how many copies of 3 enzyme clusters?
60 copies
What are three enzymes within PDC
Pyruvate dehydrogenase (E1)
Dihydrolipoyl transacetylase (E2)
Dihydrolipoyl dehydrogenase (E3)
Explain the mechanism of pyruvate conversion to acetyl-CoA
Pyruvate is taken by TPP arm, which is on enzyme 1 and the carboxylic group is removed in the form of CO2. The leftover is hydroxyethyl
Hydroxyethyl is then transferred to another prosthetic group: lipoate on enzyme 2, which becomes acyl lipoyllysine. This interacts with CoA-SH and converts to acetyl-CoA
Lipoyllysine is left in reduced form, that cannot accept incoming hydroxyethyl, so it is oxidized by third prosthetic group FAD , FAD->FADH2 and gives H2 to NAD+
TPP arm stands for
Thiamine PyroPhosphate
How many intermediates in TCA cycle
9
How many steps and enzymes are there in TCA cycle
8
What are enzymes of TCA cycle
So———-citrate Synthetase
At———-Aconitase
Another———-Aconitase
Dance———-isocitrate Dehydrogenase
Devon———-alpha-ketoglutarate Dehydrogenase
Sipped———-Succinyl-CoA Synthetase
Down———-Succinate Dehydrogenase
Five———-Fumarase
Drinks———-malate Dehydrogenase
What are 3 steps that are irreversible
Acetyl-CoA->citrate
Isocitrate ->alpha-ketogluterate
alpha-ketogluterate->succinyl-CoA
Why it is important that TCA cycle has only 3 irreversible reactions
So it has entering and exiting points for other cycles- amphybolic
How many carbons do acetyl-CoA donate
Acetyl-CoA donates 2 carbons to 4 carbon compound (oxaloacetate)
Two carbons of Acetyl-CoA do not contribute _____
Its carbons to CO2 in the first pass
Overall equation for TCA cycle
2 CO2+3NADH+1FADH2+1 ATP
What enzymes produce electron carriers in TCA cycle
NADH: isocitrate, alpha-ketogluterate
and malate dehydrogenases
FADH2:succinate dehydrogenase
At what steps we get CO2 in TCA cycle
Isocitrate ->alpha-ketogluterate
alpha-ketogluterate->succinyl-CoA
Why the step of conversion of succinyl-CoA to succinate to succinyl-CoA dehydrogenase is important
It uses ATP usually, but as it is a reverse reaction it produces one ATP
What are anaplerotic reaction
Replenishing reactions that feed TCA cycle
Citrate can be taken out of TCA for
FAs
Sterols
alpha-ketogluterate can be taken out of TCA for
Transamination->glutamate
Succinyl-CoA can be used out of TCA cycle for
Porphyrins
Heme
Oxaloacetate can be used outside of TCA
Glucoenogenic pathway
Used in AAs synthesize
Anaplerotic reactions for replenishing oxaloacetate with enzyme and in what tissues
Pyruvate->oxaloacetate (pyruvate carboxylase)->liver and kidney
Phosphoenolpyruvate->oxaloacetate with PEP carboxykinase in heart and and with PEP carboxylase
Malate can be regenerated from
Pyruvate with malic enzyme
Classical regulations of TCA cycle
By regulation of irreversible reactions. Activated by substrates, inhibited by products
an additional Pyruvate conversion regulation
by phosphorylation on enzyme 1-> inactivation
Succinyl-CoA regulates which two enzymes and for what
It inhibits citrate synthase and KDH ( alpha-ketogluterate complex) to regulate alpha-ketogluterate for AA metabolism
What ion activates TCA cycle
Ca
Do FAs contribute to gluconeogenesis
Odd number FA lead to succinate-> imbalance
Succinate enter TCA cycle->oxaloacetate->gluconeogenesis
Also acetyl-CoA can be converted to ketone bodies
Acetone can be converted to methylglyoxal or 1,2-Propanediol
Energy from ___ is used to synthesize ATP
Reduced fuels
What are reduced fuels
CHO
Lipids
AA
What happens in oxidative phosphorylation
Energy from NADH and FADH2 is used for ATP synthesis
3 types of electron carriers
Coenzyme Q
Cytochrome C
Iron-sulfur complex
What is the most important feature of coenzyme Q
It is a mobile electron carrier
Other names for coenzyme Q
(ubiquinone-oxidized or ubiquinol-reduced)
What does Coenzyme Q do
Transfers electrons from complex 1/2 to Complex 3
What happens first at electron transport chain
NADH along with another H+ donates 2 protons to iron-sulfur complex ultimately converting ubiquinine to ubiquinol
Sources of NADH
Beta-oxidation -1 NADH per cycle
Glycolysis- 2NADH
Pyruvate to Acetyl-CoA 1 NADH
AA oxidation to pyruvate, etc.
Another name of complex II in electron transport chain (ETC)
succinate dehydrogenase
What does succinate dehydrogenase do
Takes protons from FADH2 to put it ubiquinone
Acetyl-CoA dehydrogenase is present in
First enzyme for beta-oxidation
Electron transport chain (takes electrons form FADH2 and ultimately donates it to ubiquinone)
Complex I is ____ of the four complexes
The largest : 43 subunits encoded by nuclear and mitochondrial genes
How many hydrogens does complex I throw in intermembrane space
4
How many hydrogens is actually used by complex I
NADH+Q+5H+=NAD+QH2+4H
So it is actually working with 6 hydrogens
What is a cofactor for complex II
FAD
Is there a movement of hydrogens in complex II
No
What happens at complex III of electron transport chain
Ubiquinol transfers its 2 electrons to cytochrome C and oxidized coenzyme Q is thrown into the membrane. 2 hydrogens from 2 electrons are thrown out
By cytochrome C cannot accept two electrons at a time. So for now oxidized coenzyme Q get one electron and becomes an intermediate called ubisemiquinone.
At stage 2, ubisemiquinone accepts one more electron from upcoming ubiquinone and one more cycle from cytochrome C and takes 2 hydrogens form the matrix and becomes a fully reduced ubiquinol
So what is a net equation at complex III
2 cytochrome C get reduced
4 H+ get thrown out
One QH2 comes in and one Q is thrown out in the membrane
What happens at complex IV
Cytochrome donates its electrons and gets oxidized and oxygen ( as a terminal acceptor) receives electrons
Per one molecule of water how many cytochromes you need, hydrogens and oxygen you need
2
2 hydrogens
1/2 oxygen
how many electrons are pumped at complex IV
2
How many electrons do NADH and FADH2 pumps
NADH- 10H+
FADH2-6 H+
What is the equation for 1 NADH and 1 FADH2 in the electron transport chain
1NADH+11H(matrix)+1/2O2—>NAD+10H+(inter)+H2O
FADH2+6H(m)+1/2O2—->FAD+6H(inter)+H2O
What is respirosome
This word shows that electron transport chain functions as one unit
ATP synthase needs___ for synthesize of ATP
Electrochemical gradient
What systems contribute to electrochemical gradient of H+
Active transport Complex I and IV
Release of protons into intermembrane space ->oxidation of QH2 (complex III)
Chemical removal of protons from the matrix -> reduction of Q (complex I,II,III) and oxygen (complex IV)
Two subunits of ATP synthase
F0-> in the membrane-> transports protons dwon the gradient; transfers energy to F1
F1-> in the matrix-> enzymatic capacity in both directions
How many dimensions are there in ATP synthase
3 parts that are the same form alpha and beta
How three alpha and beta parts are connected
with gamma-shaft
How many hydrogens do you need for synthesis of ATP
To turn the ATP synthase itself , you need three hydrogens from intermembrane space to matrix
+
1 hydrogen in the matrix for the transfer of P to ADP
How many ATP NADH and FADH2 yield
NADH: 10/4=2.5
FADH2: 6/4=1.5 ATP
How many subunits ATP synthase do ATP
ALL of them, when the shaft turns in their direction, ATP is thrown out
How do we get NADH from the cytoplasm to matrix if the inner membrane is impermeable to NADH?
Malate-Aspartate shuttle
Oxaloacetate is converted to malate with NADH and malate dehydrogenase
Now there is malate-alpgaketogluterate trasnporter and malate is in matrix.
Malate-> oxaloacetate-> yield NADH
To balance it out, oxaloacetate is converted to aspartate with aspartate aminotrasnferase and converting glutamate to alpha-ketogluterate
Aspartate is thrown out through glutamate-aspartate shuttle
Malate-aspartate shuttle is used by
Most cells( brain and muscles as well)
What shuttle is used for NADH transport in skeletal muscle and brain
G3P shuttle
Explain G3P shuttle
NADH is used for conversion of dihydroxyacetone phosphate to G3P with cytosolic glycerol 3-phosphate dehydrogenase
G3P comes to intermembrane space, where there is mitochondrial glycerol 3-phosphate dehydrogenase bound to the inner membrane.
This enzyme converts G3P back to dihydroxyacetone and puts two hydrogens on FAD->coenzyme Q->complex 3
What shuttle yields more energy? and what is strange about it
Malate-aspartate shuttle gives more ATP because it uses NADH, but G3P shuttle uses FADH2, which is strange because G3P shuttle is in muscles that need more energy, but his shuttle is more quick, because it goes directly to respirosome
So how many ATP from complete oxidation of glucose
30 or 32
Depends on which shuttle to take NADH from cytoplasm from glycolysis to the matrix ( 2NADH->3 ATP or 5 ATP)
one palmitoyl-CoA yield how many ATPs
108
Regulation of oxidative phosphorylation
- Any substrate acts positively on the reaction, when any product inhibits
- Acceptor control of respiration (ADP). It depends on how much ADP is available , not oxygen. As soon as it gets available, respiration starts
Acceptor control is measured with
Mass action ratio ATP/ADP*P
ATP is synthesized when
It is utilized, it is synthesized as fast as it is utilized
Mitochondrial respiration in brown adipose tissue
There is uncoupling protein (UCP1). It provides an additional route for the flow of protons to the matrix.
These hydrogens lead to heat synthesize
UCP1 another name is
Thermogenin
