Metabolism 4 Flashcards
What makes acetyl-CoA so useful?
Its thioester bond is a high energy linkage which is readily hydrolysed - allows Acetyl-CoA to donate acetate (2C) to other molecules
Briefly describe what happens in the TCA/Krebs cycle.
OCI ASS FMO
-8 reactions
- starts with 2C atoms from Acetyl-CoA
- 2C combined with 4C oxaloacetate to give a 6C unit, citrate
Reaction 1 of TCA
- Oxaloacetate ——–> citrate4C ——————–> 6C
(Acetyl-CoA ——> HS-CoA + H+)
Enzyme: citrate synthase
2C acetyl group transferred to 4C oxaloacetate forming 6C citrate.
Reaction 2 of TCA
- Citrate ——–> Isocitrate
Enzyme: Aconitase
Reaction 3 of TCA
- Isocitrate ———> a-ketoglutarate6C ———————–> 5C
NAD+ ——> NADH + CO2 + H+
Enzymes: Isocitrate dehydrogenase
Isocitrate is oxidised
Reaction 4 of TCA
- a-ketoglutarate ———-> succinyl-CoA
5C ---------------------------> 4C
NAD+ —-> NADH + CO2 + H+
Enzyme: a-ketoglutarate dehydrogenase complex
Reaction 5 of TCA
- Succinyl-CoA ———> Succinate
H20------------> HS-CoA GDP + Pi ---------> GTP
Enzyme: succinyl-CoA synthetase
Whats special about GTP?
It can be used to catalyse ATP formation from ADP in the presence of a nucleoside diphosphokinase
Reaction 6 of TCA
- Succinate ————> Fumarate
FAD -------------------------> FADH2
Enzyme: Succinate dehydrogenase
Reaction 7 of TCA
- Fumarate —————–> MalateH20 INSERTED (to break double bond)
Enzyme: Fumerase
Reaction 8 of TCA
- Malate ——————–> OxaloacetateNAD+ ——————————> NADH + H+
Enzyme: Malate dehydrogenase
What does one overall turn through the TCA cycle produce?
- 3xNADH
- 1xGTP
- 1xFADH2
- 2xCO2
Where are the Krebs cycle enzymes located?
EXCEPT SUCCINATE DEHYDROGENASE
Soluble proteins in the MITOCHONDRIAL MATRIX
Where is succinate dehydrogenase located?
Firmly attached to inner surface of inner mitochondrial membrane.
It is an integral membrane protein.
How come Krebs cycle only operates under aerobic conditions?
Because NAD+ and FAD+ are only regenerated in oxidative phosphorylation when e- are transferred to O2.
How many ATPs can a NADH generate?
3
How many ATPs can a FADH2 generate?
2
How many ATPs will the oxidation of 1 Acetyl-CoA give?
12
From 1 glucose molecule, how much ATP can be derived.
Glycolysis = 8 ATP (2ATP + 2NADH)
Link = 6 ATP (2 NADH)
TCA = 24 ATP (6 NADH, 2 FADH2, 2 GTP)
=38 ATP
How are AAs degraded?
- AA group removed (excreted as urea)
2. C skeleton used for glucose production or fed into TCA cycle
Which 7 molecules can all AAs be degraded to
- Pyruvate
- Acetyl CoA
- Acetoacetyl CoA
- a-ketoglutarate
- Succinyl CoA
- Fumarate
- Oxaloacetate
Protein metabolism involves transamination reactions. What are transamination reactions?
Reaction where an amine group is transferred from an AA to a keto acid.
This forms a new pair of AA and keto acid
Describe the protein metabolism of Alanine.
- Alanine transaminated by Alanine aminotransferase
- Alanine + a-ketoglutarate —–> Pyruvate + glutamate
- Pyruvate can enter TCA cycle
- Glutamate converted back to a-ketoglutarate. Generates NH4+ which is excreted as urea.
- Loads of alanine aminotransferase may signal hepatic disorders
How does NADH from the cytosol enter the mitochondrial matrix?
- Through the Glycerol Phosphate shuttle
2. Through the Malate-Aspartate shuttle
Where is the Glycerol Phosphate shuttle located?
Skeletal muscle, brain
Where is the Malate Aspartate shuttle located?
Liver, kidney, heart
Explain the Glycerol Phosphate shuttle.
(1. e- from NADH (not the NADH itself), are carried across the mitochondrial membrane.)
2. Cytosolic G3P dehydrogenase transfers e- from NADH to G3P
3. Membrane bound G3P dehydrogenase (aka mitochondrial G3P dehydrogenase) transfers these e- to FAD.
4. From FAD, the e- get passed to coenzyme Q, which is part of the e- transport chain.
Explain the Malate Aspartate shuttle.
Overall, this is the reaction that occurs:
NADH (cytoplasmic) + NAD+ (mitochondrial) ————> NAD+ (cytoplasmic) + NADH (mitochondrial)
- H- ion transferred from cytoplasmic NADH to oxaloacetate to give malate (catalysed by cytosolic malate dehydrogenase).
- Malate transported into mitochondria where its rapidly deoxidised by NAD+ to give oxaloacetate and NADH (catalysed by mitochondrial MDH).
What is the transporter for malate?
a-ketoglutarate
What is the transporter for aspartate?
glutamate/aspartate transporter
How are the transporters able to cycle molecules around?
Transamination reactions.
Glutamate + oxaloacetate ——–> a-ketoglutarate + aspartate
Which co factor is anabolic?
NADPH is anabolic
Which co factor is catabolic?
NADH is catabolic
Compare and contrast NADP+ and NAD+.
Both can pick up a hydride ion.
Both are e- carriers.
NADP+ is similar to NAD+ except it differs as it has a phosphate group attached to a ribose ring.
Phosphate present on NADP+ means it binds to different enzymes than NAD+
How come the H- ions easily transferred to other molecules?
It is held in a high energy linkage.
