Carbohydrate Metabolism II: Aerobic Respiration Flashcards
Acetyl-CoA
- Starting substrate for the citric acid cycle
- Produced by metabolism of:
1. carbohydrates
2. amino acids
3. fatty acids
Citric Acid Cycle
AKA Kreb Cycle or TCA [Tricarboxylic Acid]
—takes place in the mitochondria
—produces:
I. NADH & FADH2
II. CO2 & H2O & Acetyl-CoA
Pyruvate Dehydrogenase
Complex of 5 enzymes that oxidize pyruvate to Acetyl-CoA in the mitochondria through an exergonic process if not inhibited by accumulation of acetyl-CoA & NADH
Constituent enzymes:
- PDH [Pyruvate dehydrogenase] ]
- Dihydrolipoyl Transacetylase ]
- Dihydrolipoyl dehydrogenase ]
- Pyruvate Dehydrogenase Kinase }
- Pyruvate Dehydrogenase phosphatase }
- ***First 3 convert pyruvate to acetyl-CoA
- ***Last 2 regulate actions of PDH
Action of Pyruvate Dehydrogenase Complex’s 3 Enzymes that Convert Pyruvate to Acetyl CoA
- PDH
I. Oxdizes pyruvate to CO2 & 2 other carbons
II. Attaches the 2 other carbons to TPP with
help of Mg2+
III. TPP oxidizes the 2 other carbons and transfers
them to lipoic acid - Dihydrolipoyl Transacetylase
I. Lipoic Acid’s disulfide group oxidizes the 2
carbons to an acetyl group
being reduced itself*
II. The lipoic acid bonds to the acetyl group through
a thioester linkage
III. Dihyrolipoyl Transacetylase transfers the acetyl-
group to CoA-SH to form Acetyl-CoA - Dihydrolipoyl Dehydrogenase
I. catalyzes reoxidation of lipoic acid through
reduction of FAD to FADH2
TPP
—–Thiamine Pyrophosphate [aka Vitamin B1]
—–a coenzyme held to PDH through noncovalent
interactions
Lipoic Acid
A coenzyme with a disulfide group, covalently bonded to dihydrolipoyl transacetylase, that reduces the 2 carbons transferred from TPP to an acetyl group
FAD
Flavin Adenine Dinucleotide
Coenzyme that reoxidizes Lipoic acid after acetyl coa has been formed
Pathways that Contribute to Acetyl-CoA Formation
- Fatty Acid Oxidation/Beta-Oxidation
I. Thioester linkage forms b/w carboxylic
acids of fatty acids and CoA-SH
2. Fatty Acyl-CoA forms & gets transported to
the transmembrane space of mitochondria
3. Fatty Acyl group gets transferred to the
carnitine via a transesterification rxn
**B/c fatty acyl-CoA cannot cross the
mitochondrial inner membrane
4. Acyl-Carnitine crosses the inner membrane
5. Acyl-Carnitine transfers its fatty acyl group to
a mitochondrial CoA-SH group via another
transesterification rxn to form acyl-CoA
6. Beta-oxidation removes the carboxylic ends of
Acyl-CoA to form acetyl-CoA - Amino-Acid Catabolism & Ketones
1. Amino acids lose their amine group through
transamination
2. Their remaining carbon cytoskeletons get
converted to ketone bodies
3. Ketones convert to acetyl-CoAs
**Acetyl-CoAs can also convert to
Ketone bodies when pyruvate
dehydrogenase complex is
inhibited* - Alcohol
1. Alcohol consumption in moderate amounts
produces Acetyl-CoA & NADH via activities of
I. Acetaldehyde dehodrogenase &
II. Alcohol dehyrogenase
**NADH accumulation inhibits the kreb
cycle, leading to fatty acid synthesis instead*****
Carnitine
Molecule that contributes to fatty acids’ oxidation to acetyl-CoA by carrying the acyl group from the cytosolic CoA-SH to a mitochondrial CoA-SH
Key Rxns of Citric Acid Cycle
- Citrate Formation
I. Acetyl-Coa & OAA couple to form Citryl-CoA
II. Citrate Synthase hydrolyzes citryl-CoA to form
1. Citrate
&2. CoA-SH - Citrate Isomerized to Isocitrate
I. Citrate attaches to Aconitase at 3 points and
loses water to form cis-aconitate
II. Cis-Aconitate reacts with Fe2+ and gains water
to form one of the four possible isocitrates - Alpha-Ketoglutarate and CO2 Formation
I. Isocitrate dehydrogenase oxidizes isocitrate to
oxalosuccinate
II. Oxalosuccinate then gets decarboxylized into
1. CO2
&2. alpha-ketoglutarate
**Rate-Limiting Step of the cycle*
1. produces NADH
2. results in loss of the first CO2 - Succinyl-CoA and CO2 Formation
I. Ketoglutarate and CoA-SH come together to
form succinyl-CoA
II. 2nd NADH gets produced, and 2nd CO2 gets
lost - Succinate Formation
I. Succinyl-CoA Synthatase hydrolyzes the
succinyl-CoA’s thioester to form
1. Succinate and CoA-SH
&2. Phosphorylated GTP [from GDP]
II. Nucleosidediphosphate Kinase transfer GTP’s
phosphate to ADP to produce ATP
**Only step of Kreb cycle that
produces ATP directly***** - Fumarate Formation
I. Succinate dehydrogenase oxidizes succinate to
fumarate in the inner mitochondrial membrane
while also reducing FAD to FADH2
**Only step that does not take place in the
mitochondrial matrix b/c succinate
dehydrogenase is a Flavoprotein (FAD) that
is only found in the inner mitochondrial
membrane* - Malate Formation
I. Fumarase converts fumarate to malate by
hydrolyzing its alkene bonds - OAA Formation
I. Malate Dehydrogenase oxidizes malate to OAA
reducing the last NAD+ to NADH
Synthases
Enzymes that form new covalent interactions without the need for significant energy input
Synthatase
Enzyme that creates new covalent interactions with significant energy input
Kreb-Cycle’s Total Products
3 NADH 1 FADH2 1 ATP 2 CO2 1 OAA
NADH= 2.5ATPs FADH2= 1.5ATPs
**Conversion of pyruvate to Acetyl-CoA yields 1 NADH*
Glycolysis Total Product Yields
2 ATPs
2 NADH
Kreb Cycle Regulation Points
- PDH Regulation
A. Phosphorylation of PDH by Pyruvate
Dehydrogenase Kinase to prevent acetyl-
CoA production when ATP levels are high
B. Dephosphorylation of PDH by Pyruvate
Dehydrogenase Phosphatase to restore CoA
production when ADP levels are high - Citrate Synthase Regulation
I. ATP & NADH & Citrate & Succinyl-CoA inhibit
Citrate Synthase allosterically - Isocitrate Dehydrogenase Regulation
I. ATP & NADH inhibit it
II. ADP & NAD+ activate it - Alpha-Ketoglutarate Dehydrogenase Complex
I. ADP & Calcium activate it
II. ATP, NADH & succinyl-CoA inhibit it
Electron Transport Chain
Exergonic Pathway that harvests electrons from electron carriers through an electron-motive force
Proton Motive Force
An electrochemical gradient generated by proton-pumping of the ETC’s complexes that allows for ADP phosphorylation and ATP generation by the energy that it stores from proton pumping
Steps of Aerobic Respiration
- Glycolysis
- Citric Acid Cycle
- Electron Transport
- Oxidative Phosphorylation
-
**Steps 3 & 4 in Detail**
1. FADH2 & NADH, formed earlier in the process, transfer their electrons to carrier proteins localized in the inner mitochondrial membrane
2. the carrier proteins in the inner mitochondrial membrane transfer the electrons as [H-] to oxygen and form H2O
* O has a greater reduction potential, therefore NADH donates its electrons to it, reducing it in the process**
Electron Transport Flow-Order
- Complex I [NADH-CoQ Oxidoreductase]
1. NADH—–e——FMN
2. FMNH2—–e——Fe-S-Oxidized
3. Fe-S-reduced——e——CoQ/Ubiquinone
* Accompanied by pumping of 4 protons to mitochondria’s intermembrane space** - Complex II [Succinate-CoQ Oxidoreductase]
1. Succinate——e——-FAD
2. FADH2———e——-Fe-Soxidized
3. Fe-S reduced——e—–CoQ
* **No protein Pumping ********* - Complex III [CoQH2-cytochrome Oxidoreductase]
1. CoQH2 ——-e—-2 Cytochrome c [w/ Fe3+]
* **Contributes to electron-Motive force through the Q cycle*****pg. 345 - Complex IV [Cytochrome c oxidase]
1. Cytochrome c——-e——-O2
* Accompanied by pumping of 2 protons**
pg. 345
CoQ Complex
Complex with over 20 subunits used to oxidize NADH
Important Subunits
- Iron-sulfur Cluster
- flavoprotein with a FMN coenzyme
FMN
Flavin Mononucleotide
A coenzyme binded to the flavoprotein of CoQ Complex important to NADH oxidation in electron transport chain and oxidative phosphorylation
Cytochrome
Proteins with heme groups in which Fe gets reduced and oxidized to Fe2+ and Fe3+ respectively during electron transport
Q Cycle
Cycle involved in Complex III of electron transport chain that contributes to electron-motive force
- —Events of the cycle****
1. 2 electrons get shuttled from a CoQH2 [ubiquinol] near the intermembrane space to a CoQ [ubiquinone] near the mitochondrial matrix
2. another 2 electrons reduce cytochrome c by attaching to their heme moieties
3. 4 protons displace to the intermembrane space in the process - **Assisted by a carrier containing Fe & S***
This cycle increases the gradient of the proton-motive force**
NADH Shuttle
Energetically costing Mechanism that enables NADH to transfer its electrons to mitochondrial inner membrane;
Reason for which cells vary in the number of ATPs that they produce by metabolism of each glucose**
NADH Shuttle Types
- Glycerol 3-Phosphate Shuttle
I. FAD-dependent Glycerol 3-phosphate
dehydrogenase transfers its e- to ETC via
Complex II after being reduced to FADH2,
yielding 1.5ATP for every molecule of
cytosolic NADH that participates in this
pathway - Malate-Aspartate Shuttle
I. OAA gets reduced to malate by oxidation of
NADH to NAD+
II. Malate crosses the inner mitochondrial
membrane to the matrix
III. Mitochondrial malate dehydrogenase reverses
the rxn, restoring NADH
IV. NADH transports its electrons to ECT through
Complex I, generating 2.5 ATP per NADH
Chemiosmotic Coupling Mechanism
- Proton motive force couples to F0 portion of ATP synthase
- Protons pumped into the mitochondrial intermembrane space flow through F0 in the direction of the gradient to the mitochondrial matrix
- F1 harnesses the energy of the electrochemical proton gradient in the process to phosphorylate ADP to ATP
ATP synthase
Enzyme that drives ADP phosphorylation in oxidative phosphorylation after ECT
Has 2 portions:
- F0: is an ion channel
- F1: enzyme that harnesses energy of electrochemical gradient of the proton motive force to generate ATP from ADP
Chemiosmotic Coupling
Mechanism that explains oxidative phosphorylation by describing a direction relationship b/w ATP synthase and proton gradient
Oxidative Phosphorylation Debated Mechanisms
- Chemiosmotic coupling
2. Conformational Coupling
Conformational Coupling
Oxidative phosphorylation mechanism that describes an indirect relationship b/w the ATP synthase and proton gradient , stating that F0 spins within a stationary compartment to harness ATP from the gradient
**Gradient causes conformational change; Synthase releases ATP*review 348
