What are the products of one turn of the TCA cycle?
3 x NADH 1 x FADH2 1 x GTP 2 x CO2
Where are the Krebs’ Cycle enzymes found?
Mitochondrial Matrix
Which Krebs’ Cycle enzyme is not found in this location?
Succinate Dehydrogenase
What happens in Transamination?
An amine group is transferred between an amino acid and a keto acid to generate a new amino acid and keto acid (the basis of the malate-aspartate shuttle) EXAMPLE: alanine + alpha-ketoglutarate pyruvate + glutamate (enzyme = alanine aminotransferase)
What are the two ways of electrons from NADH entering the mitochondrial matrix? Where are these two transport mechanisms found?
Glycerol Phosphate Shuttle – skeletal muscle, brain Malata-Aspartate Shuttle – liver, kidney, heart
Describe the glycerol phosphate shuttle.
Cytoplasmic glycerol-3-phosphate dehydrogenase transfers electrons from NADH to dihydroxyacetone phosphate converting it to glycerol-3-phosphate Glycerol-3-phosphate is converted by mitochondrial glycerol-3-phosphate back into Dihydroxyacetone phosphate and the electrons are passed via FAD to coenzyme Q
What different types of reactions are NADPH and NADH involved in?
NADPH = Anabolic NADH = Catabolic
anabolic is building up
catabolic is breaking down
What are the components involved in the malate-aspartate shuttle?
Malate (in) Alpha-ketoglutarate (out) Oxaloacetate (converted from malate) Glutamate (in) Aspartate (out)
what are the 6 types of metabolic reaction? explain ones i dont know
- reduction and oxidation - ligation requiring ATP cleavage (Formation of covalent bonds) - Isomerisation (Rearrangement of atoms to form isomers) - Group Transfer (transfer of the functional group from one molecule to another) - Hydrolytic (cleavage of bonds by the addition of water) - Addition or removal of functional groups (this is the formation or removal of double bonds)
how is acetyl CoA made from pyruvate?
pyruvate + Hs - CoA ——> acetyl CoA + CO2 this happens in the mitochondria and then moves into the krebs cycle
what is a description of the TCA cycle?
A continuous cycle of eight reactions, starting with 2 carbon atoms from acetyl CoA being condensed with the 4 carbon unit of oxaloacetate to give a 6 carbon unit, citrate
what is reaction 1?
- : Oxaloacetate (4C) + ——> Citrate (6C) the enzyme is citrate synthase 2C acetyl group from acetyl CoA is transferred to the 4C oxaloacetate to form 6C citrate
what is reaction 2?
Citrate (6C)———–> Isocitrate (6C) - Citrate is isomerised to give isocitrate Enzyme = Aconitase
what is reaction 3?
Isocitrate (6C) —————> a- ketoglutarate (4C) Isocitrate is OXIDISED to form a-ketoglutarate changing from 6C to 5C - the enzyme is isocitrate dehydrogenase
what is reaction 4?
a-ketoglutarate ———–> succinyl-CoA - Similar to reaction catalysed by Pyruvate Dehydrogenase Complex - changes from 5C - 4C - Enzyme = a-ketoglutarate dehydrogenase complex
what is reaction 5?
succinyl-CoA ————-> Succinate both 4 C - CoA is displaced by phosphate molecule which is transferred to GTP - Enzyme = succinyl CoA synthetase - GDP + Pi —> GTP
how does GTP / GDP work?
GTP + ADP —> GDP + ATP
using enzyme nucleoside diphosphokinase
what is reaction 6?
Succinate (4C) ———-> Fumarate (4C) - Succinate is OXIDISED and some FADH2 is generated from FAD - Enzyme = succinate dehydrogenase
what is reaction 7?
Fumarate————-> Malate - Addition of water molecule breaks a double bond - enzyme = fumarate
what is reaction 8?
Malate ———> Oxaloacetate Dehydrogenation of malate to give oxaloacetate -Enzyme = malate dehydrogenase
what does one turn of the krebs cycle give?
• 3 x NADH • 1 x GTP • 1 x FADH2 • 2 x CO2 - 2 x ATP
where are most of the krebs cycle enzymes? what is the exception?
soluble proteins located in mitochondrial matrix space. SUCCINATE DEHYDROGENASE - this is an integral membrane protein which is attached to the inner surface of inner mitochondrial membrane
what conditions does the krebs cycle work under?
operates under AEROBIC CONDITIONS because of NAD+ and FAD being regenerated
how much ATP does the reoxidation of co factors via oxidative phosphorylation make?
- 1 NADH –> 3ATP - 1FADH2 –> 2ATP - 1GTP –> 1 ATP therefore one acetyl CoA (3x NADH) + (1x FADH) + ( 1x GTP)
what is the theoretical maximum yield of ATP?
what is the general strategy of degradation of amino acids?
- Amino Acid group is removed (eventually excreted as urea)
- Carbon skeleton is either funnelled into production of glucose or fed into krebs’ cycle.
what does the degradation of all 20 amino acids give rise to?
- pyruvate
- acetyl CoA
- Acetoacetyl CoA
- a-ketoglutarate
- Succinyl CoA
- fumarate
- oxaloacetate
what is a transamination reaction?
- a reaction in which an amine group is transferred from one amino acid to a keto acid thereby forming a new pair of amino and keto acids.
where does transamination come into role in cell metabolism?
- Alanine undergoes transamination by the action of enzyme Alanine Aminotransferase
- Pyruvate can enter the TCA cycle
- Glutamate is converted back to a-ketoglutarate by Glutamate Dehydrogenase, this also makes NH4+ which is converted back to urea
what do high levels of alanine aminotransferase suggest?
hepatic disorders … eg Hep C
why does the NADH need to be moved from glycolysis to be used in oxidative phosphorylation?
- to regenerate NAD+
- There is only a finite amount of NAD+ so unless it’s regenerated, glycolysis will stop
how does the NADH cross the cytosol?
- The NADH cross the cytosol into the matrix of the mitochondrion by:
- Glycerol Phosphate Shuttle - skeletal muscle, brain
- Malate-Aspartate Shuttle - liver, kidney, heart
how does the glycerol phosphate shuttle work?
Electrons from NADH, rather than NADH itself are carried across the mitochondrial membrane via a shuttle.
Cytosolic glycerol-3-phosphate dehydrogenase transfers electrons to Dihdroxyacetone phosphate to form glycerol 3-phosphate
A membrane bound form of the same enzyme transfers the electrons to FAD. The electrons then get transferred to co-enzyme Q, part of the electron transport chain
how does the malate-aspartate shuttle work?
Uses 2 membrane carriers + 4 enzymes.
- Hydride Ion (H-) is transferred from cytoplasmic NADH to oxaloacetate to give malate (catalysed by cytosolic malate dehydrogenase (MDH)).
- Malate is transported into mitochondria where it is rapidly re-oxidised by NAD+ to give oxaloacetate and NADH (catalysed by mitochondrial MDH).
are NADPH and NADH anabolic or catabolic?
NADPH = anabolic
NADH - catabolic
why is NADPH important in cholesterol synthesis?
- NADPH helps catalyse the final reaction of many, that leads to cholesterol synthesis
- The C=C double bond is reduced by the transfer of a hydride ion
what is NADP+ ?
NADP+ is similar to NAD+, the only differing by a phosphate group attached to one of the ribose rings.
Like NAD+, NADP+ can pick up two high-energy electrons and a proton collectively known as a hydride ion (H-).
NADP is an electron carrier
the phosphate group does not participate but it has a different structure so it can bind to different enzymes than NAD+