Week 4 - Metabolism 1 Flashcards
What is metabolism?
The complete set of catabolic and anabolic reactions that occur within living cells
What is catabolic breakdown?
Biochemical reactions that ‘break down’ molecules into smaller ones
What is an anabolic reaction?
Biochemical reactions that synthesis large molecules from smaller ones
What are the components of catabolic pathways?
- protein breakdown
- lipid oxidation
- carbohydrate oxidation
- nucleotide hydrolysis
What are the components of anabolic pathways?
- protein synthesis
- lipid synthesis
- carbohydrate synthesis
- nucleotide synthesis
Catabolic reactions are..
exergonic (energetically favourable)
Anabolic reactions are…
endergonic (energetically unfavourable)
What does a larger change in G mean?
Means that ATP is very ‘willing’ to transfer uts phosphates. This in turn relates to the structure of ATP and uts hydrolysis products
How do cells obtain energy?
Cells obtain energy through oxidation of organic molecules (food).
Energy is stored in covalent bonds of these organic molecules
What happens to a NADH and NADPH?
They ‘pick up’ energy in the form of 2 high energy electrons and a proton (a hybride ion)
What is the most important molecule for metabolism?
Acetyl CoA
How could we describe a reaction of -10 change in G?
exergonic reaction/ energetically favourable
Why must anabolic reactions normally be coupled to catabolic reactions?
Because anabolic reactions are endergonic and require energy
What is meant by a redox reaction?
a reaction where one molecule is reduced and another is oxidised
What is the function of activated carrier molecules?
to transfer energy from one reaction/pathway to another
Which metabolic intermediate is common in energy generation from fat, carbohydrate and protein?
Acetyl CoA
Does glycolysis occur in the absence of oxygen?
Yes but does involve oxidation
How many reactions does glycolysis consist of?
10
Why is ATP hydrolysed in reactions 1 to 3?
- phosphorylate the sugar
- couple the reaction to make it energetically favourable
What is reduced in glycolysis?
NAD
What is generated from glycolysis?
ATP
What occurs during Step 1 of glycolysis?
- Glucose phosphorylated by Hexokinase (traps glucose)
- Glucose has transporters which allow it to move in and out of the cell
- Glucose - 6 - phosphate cannot access these transporters
- The phosphate group comes from ATP = ADP + Pi
- irreversible step
What are kinases?
Enzymes that add phosphate groups to molecules
What occurs during Steps 2 - 3 of glycolysis?
- Glucose - 6 - phosphate undergoes isomerismation to Fructose - 6 - phosphate
- Then Fructose - 6 phosphate is phosphorylated to form Fructose 1,6-biosphosphate
(preparing glucose so that is can be used to generate more energy)
What occurs during Step 4 of glycolysis?
- Aldolase splits F 1,6-BP into 2 x 3C molcules (two isomers)
- G-3-P is on the glycolysis pathway
- Dihydroxyactone phosphate is not
What occurs during Step 5 of glycolysis?
- Dihydroxyacetone phosphate is an isomer of G-3-P and can be easily converted
- 2 x molecules of G-3-P are generated
What occurs during Steps 6-10 of glycolysis?
- forms a carboxylic acid with high phosphate transfer potential
- Generates 2 x ATP and 2 x NADH
- end product is pyruvate
Summarise Step 6
- enzyme 1 binds to G-3-P and catalyses its oxidation
- NAD+ accepts the elctrons and is reduced
- enzyme is displaced by Pi to create a high energy sugar-phosphate called 1-3-biphophoglycerate
Summarise Step 7
- This intermediate binds to enzyme 2 which catalyses the transfer of Pi to ADP, this creating ATP and generating a carboxylic acid called 3-phosphoglycerate
Where does lactate come from?
NAD+ must regenerate to enable glycolysis to continue. When no oxygen is available to act as an electron acceptor NADH passes the electrons to pyruvate to from lactate.
What is PFK?
It is the most important regulatory and rate limiting enzyme in glycolysis
What is PFK activated by?
AMP
F 2,6, BP
What is PFK inhibited by?
ATP
lower pH as lactate
Citrate
What is gluoneogenesis?
The formation of glucose from non-carbohydrate precursers
eg, lactate, glucogenic amino acids and glycerol
Where does gluoneogenesis occur?
in the liver
as the liver is responsible for maintaining blood glucose
What occurs during glucneogenesis?
essentially it is the reverse of glycolysis (pyruvate - glucose)
What occurs during Step 1 of gluconeogenesis?
- pyruvate carboylast has a biotin prosthetic group
- serves as a CO2 carrier
- biotin is not carboxylated unless acetyl coA is present (allosteric regulation)
Where does the enzyme pyruvate carboxylase come from?
present in the mitochondria
What is biotin?
Biotin is an activated carrier of CO2
What occurs during Step 2 of glucose-genesis?
- PEP carboxylase is a cytosolic enzyme
- Oxaloacetate needs to escape from the mitochondria but it needs converting to malate first as in the form oxaloacetate it cannot leave the mitochondria
- Then the malate gets oxidised back to oxaloacetate
What occurs during the cori cycle?
Lactate - pyruvate + 6-P - glucose
What happens to lactate produced in the muscle during heavy exercise?
1- It can be taken up by some tissues eg the heart and converted back to pyruvate and used for energy (TCA cycle)
2 - Be transported to the liver and converted back to glucose via the cori cycle
What is the net ATP yield of glycolysis?
2 ATP
What is the biochemical reason for lactate formation from pyruvate?
To quickly regenerate NAH+ for use in glycolysis. It would be necessary when energy is needed very quickly, or oxygen is limiting
Which reactions of glycolysis do you think are most energetically favourable?
The ones that can be used to make ATP (must be lots of energy left over to do this) and or the ones that are coupled to ATP hydrolysis, because ATP hydrolysis releases lots of free energy.
Reactions 1,3,10 are very energetically favourable
What is the main regulatory enzyme of glycolysis? and by what mechanism is it regulated?
Phosphofructokinase (step3), regulated allosterically
Thermodynamically explain why gluconeogenesis isnt the direct reversal of glycolysis
Because steps 1,3,10 of glycolysis are so energetically favourable , they are essentially irreversible
What is the role of biotin in gluneogensis?
Biotin is the prosthetic group of pyruvate carboxylase. Binds CO2 and transfers it to pyruvate to form oxaloacetate at the start of gluconeogenesis.
How does the TCA cycle start?
pyruvate moves into the mitochondria where it is decarboxylated to form acetyl coA
What occurs during pyruvate dehydrogenase complex reaction?
- huge enzyme (bigger then most ribosomes)
- 3 enzymes in one
- very complex 4 step reaction
- NADH is generated to enable efficient recycling of the enzyme
- irreversible reaction
What occurs during the rest of the TCA cycle?
- Acetyl CoA (2-C) condenses with 4-C oxaloacetate to form 6-C tricarboxylic acid, citric acid
- 8 more reactions (4 oidation reactions) regenrate oxaloacetate
- energy released from reactions is captured in
- 3x NADH
- 1 x FADH2
- 1 x GTP
What is citrate synthase?
- binds to oxaloacetate then acetyle coA
- an intermediate Enol is formed from Acetyl COA which attacks oxaloacetate and forms citryl coA
- citrate synthase can only hydrolyse citryl coA
- thus preventing Acetate and CoA formation
What 2 enzymes are regulated allosterically during the TCA cycle?
1 - Isocitrate dehydrogenase
2 - alpha-ketoglutarate dehydrogenase
What is isocitrate dehydrogenase stimulated by?
ADP
NAD+
Isocitrate
What is isocitrate dehydrogenase inhibited by?
ATP
NADH
What is alpha-kenoglutarate dehydrogenase stimulated by?
ATP
What is alpha-ketoglutarate dehydrogenase inhibited by?
Succinyl CoA
ATP
NADH
When does Biotin get carboxylated?
only when Acetyl CoA is present (allosteric regulation)
What is anapleurosis?
Reactions that replenish TCA cycle
Why is PDH reaction considered irreversible? And what are the consequences of this
Irreversible as it is so energetically favourable. That means that acetyle CoA cannot be converted to pyruvate. Pathways that generate acetyl coA can therefore not enter the gluconeogenic pathway
What are the products of each turn of the TCA cycle?
3 x NADH
1 x FADH
1 x GTP
Why is it important that citrate synthase cannot hydrolase Acetyl CoA directly?
If it hydrolysed Acetyle CoA directly, it would result in acetate and CoA as products and this would not facilitate the generation of energy through the TCA cycle
What is meant by an analeurotic reaction?
A reaction that replenishes TCA cycle intermediates
Why do you think the TCA cycle is considered aerobic?
This relates to the use of oxygen downstream of the TCA cycle in the respiratory chain. In the respiratory chain, oxygen is required to accpet electrons from NADH and FADH and regerate NAD and FAD for the TCA cycle. If no oxygen was present, then NADH and FADH would accumulate and the TCA cycle would halt.
