Session 2 Lecture Notes Flashcards
Before pyruvate enters TCA cycle what is it converted to?
What enzyme involved?
Carbon numbers?
Pyruvate to Acetyl CoA
Enzyme: pyruvate dehydrogenase
Carbons: 3 carbon sugar to 2 carbon sugar
Where does the energy come from at start of Krebs cycle to convert pyruvate to Acetyl CoA and NAD+ to NADH?
Chemical bond in carboxyl group of pyruvate
Where is pyruvate dehydrogenase (PDH) found?
In the mitochondrial membrane
What is PDH sensitive to?
Vitamin B1 deficiency
What are high energy regulators of PDH?
They inhibit PDH Examples: The product = Acetyl CoA NADH ATP citrate
What are low energy regulators of PDH?
They increase PDH activity (dephosphorylation) Examples: Substrate = pyruvate CoA NAD+ ADP Insulin
At start of Krebs cycle what does Acetyl CoA combine with?
What does it produce?
How many carbons involved?
Combines with Oxaloacetate (4 carbon sugar)
To produce citrate (6 carbon)
What is isomerisation?
When one molecule is converted to another molecule with exactly same atoms but different arrangement
Is conversion of isocitrate to alpha-ketoglutarate an oxidative step?
What is involved in reaction?
Is it irreversible?
Yes it is as loss of carbon (C6 to C5)
Loss of carbon means irreversible
NAD+ is reduced to NADH
What co-factor is involved in conversion of alpha-ketoglutarate to succinyl-CoA?
Carbon number gain or loss?
How is the energy maintained?
Alpha-ketoglurate is oxidised to Succinyl-CoA (5 carbon to 4 carbon) so irreversible step
Co-factor CoA is involved which also maintains the the high energy bond in molecule
NAD+ is also reduced to NADH
The enzyme in the Krebs cycle converts Succinyl-CoA to?
Succinate + CoA - the release of CoA providing the energy to convert GDP to GDP
What is at the end of the Krebs cycle?
What happens in cycle?
Oxaloacetate (back to start of cycle) Release of carbons and removal of reducing equivalents 2 CO2 released 3 NADH 1 GTP 1 FADH2
What is substrate level phosphorylation?
Reaction that results in formation of ATP or GTP by transfer of phosphoryl group from a phosphorlayted compound to ADP or GDP
As glucose = 2 pyruvate molecules you get 2 turns of Krebs cycle. Bearing this in mind what is total end gain/loss from 1 glucose?
Loss of 4 carbons
6 NADH
2 GTP
2 FADH2
What is the enzyme that converts isocitrate to alpha-ketoglurate?
Isocitrate dehydrogenase
because the H+ is used to reduce NAD+ to NADH
What enzyme converts alpha-ketoglutamate to succinyl-CoA?
What co-factor is used?
Alpha-ketoglutarate dehydrogenase
(because the H+ is used to reduce NAD+ to NADH)
Co-factor = CoA
Where does stage 4 of metabolism take place?
In the inner mitochondrial membrane
What are the 2 processes involved in stage 4 of metabolism?
- Electron transport
2. Oxidative phosphorylation (free energy released used to drive ATP synthesis)
What part of the mitochondria is highly impermeable?
The inner membrane
What is used to move hydrogens into intermembrane space?
Where does the energy for this come from?
Proton translocation complexes 1,2 and 3
Electrons are used from oxidatation of NADH and FADH2
What % of energy is used to create proton gradient across mitochondria and what is the rest of the energy used for?
30% used to create proton gradient
Remaining 70% used to maintain core body temp at approx 37 degrees
What enzyme is used coupled with proton motive force to move H+ back into inner membrane down electrochemical gradient?
Why does it require an enzyme?
What is synthesised in process?
Enzyme = ATP synthase
Needs to use enzyme because the inner mitochondrial membrane is impermeable
Energy is used to drive synthesis of ATP
Name 3 ways in which ATP synthesis in mitochondria is reduced
1) Increase in ATP levels = decrease in ADP so ATP synthase has no substrate to drive synthesis
2) Inhibition of oxidative phosphorlyation by poisoning eg cyanide or CO
3) Uncoupling molecules give increase permeability of inner membrane for H+ and prevent ATP synthesis
What are triacylglycerols composed of?
Three fatty acid chains and a glycerol backbone (containing 3 carbons)
Are triacylglycerols hydrophobic and where are they stored?
Yes there are - stored in anhydrous form within adipose tissue as lipid droplets
Where does metabolism of triacylglycerols take place?
What enzyme cleaves triacylglycerol and into what?
Extracellular in GI tract
Enzyme pancreatic lipase cleaves triacylglycerol into fatty acids and glycerol
Fatty acids can be oxidised
to provide energy. However where can’t this take place and why?
It takes place in mitochondria
Therefore can’t take place in RBCs because they have no mitochondria
Can’t take place in brain because fatty acids can’t cross blood brain barrier
Where are fatty acids and glycerol repackaged in metabolism and where do they go to?
What are they transported as?
They are repackaged in small intestine epithelium and transported as chylomicrons (as TAGs are hydrophobic) to either consumer tissues or adipose tissue (when in excess)
What is difference between saturated and unsaturated fatty acids?
Saturated = all single bonds between carbons acids in chain Unsaturated = double bonds between carbons
Give an example of a polyunsaturated fatty acid that is essential and why?
Linolenic acid
Essential because mammals can’t produce double bonds between carbons beyond C9 in chain
How are fatty acids activated?
Where are they activated?
Activated by Acetyl-CoA
In the cytoplasm
How do fatty acids cross mitochondrial membrane to be oxidised?
Using a carnitine shuttle
In the oxidation of fatty acids in mitochondria, how many carbons are removed at each stage and what reducing equivalents are created?
2 carbons removed at each stage
Carbons used to create reducing equivalents (NAD+ to NADH and FAD+ to FADH+)
These are used in electron transport chain and oxidative phosphorylation to generate ATP
How are fatty acids linked to Acetyl CoA?
By enzyme fatty acyl CoA synthase
It uses energy from hydrolysis of ATP to AMP + 2 Pi
What enzymes are used in carnitine shuttle transporter? (moving carnitine across impermeable inner mitochondrial membrane)
CAT1 and CAT2
Carnitine acyltransferase 1 & 2
Where are ketone bodies synthesised?
What are they synthesised from
and when?
In the liver mitochondria
Synthesised from HMG (hydroxymethyl glutaric acid) when glucose levels are low
What is marasmus?
Insufficient energy intake - thin emaciated appearance
In marasmus where does the energy sources come from?
1) Fatty acids are released from adipose tissue and converted to ketone bodies
2) Brain and RBCs can’t use ketones so they get glucose from glycogen stores in liver
3) When glycogen stores run out muscle protein is broken down to release AAs for glucose synthesis
What is kwashiokor?
Low protein intake (so essential AAs from diet not being obtained) and swollen abdomen
In kwashiorkor name 2 things the liver is unable to synthesis & what does this lead to?
Liver is not able to synthesis
1) lipoproteins (chylomicrons) to transport fat around body in blood - fat builds up liver
2) serum albumin and other serum proteins - leads to oedema due to reduced oncotic pressure
In kwashiorkor what happens to urea cycle?
The enzymes in the urea cycle are downregulated
