Week 5 - Metabolism 2 Flashcards
How are fatty acids stored?
Triacly glycerol
What are fats important for?
energy generation - great store of energy
What do fats form?
cell membranes
What are fats precursers for?
Hormones and intracellular messengers
What is the chemical structure of fats?
- uncharged
- highly reduced and non-polar
- do not like water
What is the equation for Lipolysis?
TAG = 3x fatty acids + glycerol
by lipase (enzyme which breaks it down)
Where are fatty acids activated?
on the outer mitochondrial membrane
What is the 1st Step of fatty acid activation?
Fatty acid reacts with ATP to form an acyl adenylate which is a carboxyl group of fatty acid bound to phosphate of AMP.
Ppi is removed and further hydrolysed. This drives the reaction forward
What is the 2nd Step of fatty acid activation?
The sulfhydryl group of CoA attacks the acetyl adenylate to form Actyl CoA (thioester bond)
AMP is removed
Where does oxidation of fatty acids occur?
in the mitochondria
What enzyme helps carnitine from acyl carnitine?
CPT 1
changes Acetyl CoA to CoA
What enzyme helps acyl carnitine from carnitine?
CPT 2
Changes CoA to Acetyl CoA
What is this process called?
Translocase
What is the cofactor of Translocase?
Carnitine
What are the 4 steps of Beta oxidation?
1 - Oxidation by FAD
2 - Hydration
3 - Oxidation by NAD+
4 - Thiolysis by CoA
These reactions reduce the number of carbons on the fatty acyl CoA
What does each cycle of Beta oxidation produce?
- Acetyl CoA
- NADH
- FADH2
When will the cycle stop?
Will stop when the fatty acid is completely degraded
What are saturated fatty acids?
No double bonds between carbon atoms, so all carbonds are saturated by bonds to hydrogen
What are unsaturated Fatty acids?
contain double bonds between carbon atoms, so there are less hydrogens
What happens during oxidation of unsaturated fatty acids?
- Palmitoleoyl CoA is a 16C fatty acyl CoA
- it has a single double bond in cis
- the first three beta oxidation cycles occurs as normal
- but cis 3-enoyl CoA is not a substrate for acetyl coA - dehydrogenase (step 1)
- an isomerase converts it into trans which is a substrate
What are peroxisomes?
Fatty acids can be oxidised in these organelles
oxidation is identical but the H2 being passed from FADH to O2 to form H2O2
What does it mean if glycolytic flux is low?
There is low pyruvate = low oxaloacetate
What happens to oxaloacetate if glucose levels are low?
It is used in gluconeogenesis
When can Acetyl coA enter TCA cycle?
Can only enter if there is sufficient oxaloacetate to react/condense with
What happens if the concentration of Acetyl coA rises?
It is diverted to the production of Ketone bodies
What occurs during Ketogenesis?
- reverse of last step in beta oxidation - now releasing coA-SH
- hydrolysis of the thioester on Acetyl CoA linage drives this reaction forward (makes it favourable)
- Acetoacetate can be reduced by NADH if NADH levels are high
- some acetoacetate is spontaneously decarboxylated to acetone.
Where does Ketogenesis occur?
in the liver
How are ketones used within the body?
Many tissues such as the heart and kidney use ketones in preference to glucose
the brain will use ketones during starvation
Define the biochemical structure of tricylglycerol?
3 fatty acids + glycerol
Through what pathway can glucose be generated from glycerol?
gluconeogenesis
Why do you think FADH2 is produced in the first step of beta oxidation instead of NADH?
There is not sufficient energy produced to form NADH, so FADH2 is the nect best thing
What is the final oxidised molecule of beta oxidation and what is its typical fate?
Acetyl CoA - enters TCA cycle
Provide a sitation under which Acetyle CoA would not enter the TCA cycle and would be converted to a ketone instead?
When glucose levels are low within the cell, acetyl coA will be diverted to generate ketone bodies. Providing fuel for important tissues such as the brain/heart. Acetyle CoA only enters the TCA cycle when there is sufficient oxaloacetate for it to condense with, under low glucose conditions oxaloacetate is diverted to make glucose and cant be replenished because pyruvate levels will be low. Occurs due to diabetes or starvation.
What is the carrier molecules equivalent to CoA but for fatty acid synthesis?
ACP
What is fatty acid synthesis?
The elongation of a fatty acid chain by sequential addition of 2C units derived from Acetyl CoA
What is acetyl CoA catalysed by?
Acetyl CoA carboxylase (ACC)
What is wrong with CoA for fatty acid synthesis?
ACP acts as a carrier that holds the growing fatty acid chain and trasnports it between the different enzyme active sites of the fatty acid synthase complex
What is formed after the first stage of fatty acid synthesis?
acetyl ACP
Malonyl ACP
What form does fatty acid synthase exist as?
a dimer
The process of fatty acid synthesis
- acetyl ACP condenses with malonyl ACP to form a 3-ketoacyl ACP
- This unfavourable reaction is overcome by the release of CO2 of malonyl ACP
- The 4C product is reduced and dehydrated to form Butyryl ACP
- Butryrl ACP condenses with another Malonyl ACP and the cycle continues
- formation of a C16 is detected by a thioesterase that cleaves ACP generating palmitate
Where are longer fatty acids generated?
on the cytosolic membrane of the ER
- malonyl CoA is the donor
- decarboxylation drives the reaction forwards
How is fatty acid synthesis regulated?
- AMPK senses energy levels of the cell
- when energy levels is low AMPK phosphorylates ACC
- This inactivates ACC
How does acetyl transfer from the mitochondria to the cytosol?
- Acetyl is converted to citrate (TCA cycle)
- citrate is transported into the cytosol
- ATP citrate lyase (reductive TCA cycle enzyme) then converts citrate to oxaloacetate regenerating Acetyl CoA
What is the pentose phosphate pathway?
a crucial source of NADPH in non-photosynthetic organisms
What are the 2 phases of the pathway?
1 - oxidative phase which generates NADPH
2 - non-oxidative phase which interconverts sugars
How many NADPH are generated in the oxidative phase?
2
What regulates the pentose phosphate pathway?
cells requirement for ATP
ribose - 5 - phosphate
What is generated by the non-oxidative phase?
2 x NADPH
2 x F-6-P
1x G-3-P
What would happen if a cells needed NADPH and R-5-P?
The oxidative phase predominates and NADPH and R-5-P are synthesised
What would happen if a cell needed NADPH but didnt require R-5-P?
- both phases of PPP occur
- generating NADPH, F-6-P, G-3-P
- F-6-P and G-3-P enter gluceogenic pathway
- G-6-P is resynthesised and the PPP can undergo another round
What would happen if the cell needed NADPH and ATP?
- both phases of PPP occur
- F-6-P and G-3-P enter glycolysis and ATP is synthesised
Provide 2 reasons why the Acetyl CoA carboxylase reaction is irreversible under physiological conditions?
hydroylsis ATP and there will always be more acetyl CoA then malonyl CoA, this makes the change in G negative and therefore exergonic so irreversible
How many NADPH molecules are synthesised per acetyl coAA that enters fatty acid synthesis?
one
Which tissues might be expected to have very active Pentose Phosphate Pathways?
The PPP makes NADPH which can be used for a range of biosynthetic reactions, fatty acid synthesis. adiopose, adrenal, mammory glands
How would ribose 5 phosphate be used if the cell required energy?
It would be converted to frukto-6-phosphate and G-3-P via the non oxidative phase of the PPP. Those intermediates would then generate ATP via glycolysis
How can amino acids be used in metabolism?
amino acids can be degraded and used as fuel
where is the site of amino acid degradation?
the liver
What happens during transamination?
the amino group of the amino acid is transferred to a keto acid
then catalysed by enzymes called aminotransferases
What happens when oxaloacetate accepts an amino acid?
forms an asparate which is required for urea formation
can also be transaminated to form glutamate
What is the process deamination?
removal of the amino group
redox
catalysed by gluamate dehydrogenase
what is the purpose of the urea cycle?
to get rid of the toxic ammonia
state the major site of amino acid metabolism
the liver
why cant all amino acids be immediately deaminated?
the body doesnt have the correct enzymes to do all 20 amino acids
why is it important for deamination to occur in the liver?
because the liver has enzymes required for the urea cycle - removes ammonia
Why are leucine and lysine considered to be solely ketogenic amino acids?
they are converted to acetyl coA. pyruvate dehydrogenase reaction is irreversible and acetyl coA cannot be converted to pyruvate so cannot form glucose
Describe why the amino acids asparate can be converted to either oxaloacetate or fumarate?
via transmutation, converted to oxaloacetate
asparate can also enter the urea cycle to provide the additional nitrogen required to form urea.
some of the carbons form asparate and captured in fumarate, leaving urea cycle
What happens during the glucose-alanine cycle?
- muscle uses BCAAs for fuel during prolonged exercise
- muscles doesn have urea cycle
build up of glutamate pushes reaction to the left - alanine is released into the blood and taken up by the liver
- alanine is transaminated and the amino acid group is removed.
