energy metabolism Flashcards
example of anabolic process
bonding of amino acids to make proteins
example of catabolic process
glucose breakdown
where do cells get energy from
nutrients or fuels such as carbohydrates lipids or proteins
what is the structure of ATP
adenine base
ribose sugar
3 phosphate groups
it has high energy bonds
what happens when ATP is hydrolysed
Phosphate and heat energy is released
The reaction is energetically favourable - negative gibbs freee energy
What is glycolysis
anaerobic breakdown of glucose to pyruvate
small amount of ATP generated by substrate level phosphorylation
what is Krebs cycle
Oxidation of acetyl CoA to Co2
Generates co enzymes NADH and FADH2
generates ATP
what is oxidative phosphorylation
transduction of energy derived from fuel oxidation to high energy phosphate
generates large amounts of ATP
what pathways is glucose metabolism linked to
Glycolysis
Krebs cycle
Oxidative phosphorylation
where does glycolysis occcur
in cytosol under anaerobic conditions
why does glycolysis occur (2)
it’s an emergency energy production pathway when oxygen is limited
it generates precursors for biosynthesis
- G-6-P converted to ribose 5-P via pentose phosphate pathway
- G-1-P for glycogen synthesis
- pyruvate is transaminated to alanine
- substrate for fatty acid synthesis
- glycerol -3-P is backbone of triglycerides
what are the products of glycolysis
2 molecules of pyruvate (C3H4O3)
2NADH + H+
2 ATP
Overview of glycolysis
Glucose enters cells through diffusion
Glucose is phosphorylated on 6th carbon
Phosphate group has come from ATP hydrolysis
This is catalysed by hexokinase
This produces glucose 6 phosphate
This is isomerised to fructose 6 phosphate by glucose isomerase
Another phosphate is added to carbon 1 to produce fructose 1,6 biphosphate
Catalysed by phosphofructokinase
Produced fructose 1,6 biosphopate
this is an unstable molecule that will split spontaneously to form two 3 carbon molecule and consumes the second molecule of ATP
fructose-1,6-bisphosphate is converted into dihydroxyacetone phosphate and glyceraldehydr 3- phosphate, catalysed by fructose-bisphosphate aldolase
DHAP is converted into a second molecule of GA3P.
1 NADH and 2 ATP are produced per molecule of GA3P entering the pathway.
As our first molecule of glucose has generated two molecules of GA3P, the total payout from the payout phase is 2 NADH + 4 ATP.
As we used 2 ATP in the investment phase, the net gain from our first molecule of glucose is 2 NADH and 2 ATP
6, GA3P is converted into 1,3-bisphosphoglycerate (1,3-BPG) by glyceraldehyde phosphate dehydrogenase - yields a molecule of NADH, formed by the reduction of NAD+
1,3-BPG is converted into 3-phosphoglycerate (3PG) by phosphoglycerate kinase - generates a molecule of ATP
3PG is converted into 2PG by phosphoglycerate mutase
2PG is converted into phosphenolpyruvate by enolase.
Phosphenolpyruvate is converted into pyruvate by pyruvate kinase, which yields our second molecule of ATP. This is irreversible, and is therefore another key regulatory step
what is allosteric regulation
binds to a non catalytic site
conformational change
increases or decreases affinity for the substrate
what is hormonal regulation
increases or decreases gene expression of the enzyme
indirect route - through affecting regulatory molecules (usually kinases or phosphatases)
increases or decreases enzyme activity
how are proteins broken down
protein –> amino acids –> amine –> urea
how are carbohydrates broken down
carbohydrates –> glucose –> glycolysis –> acetyl coA –> krebs cycle
what is the equation for glycolysis
Glucose + 2ADP + 2Pi + 2NAD+ > 2 Pyruvate + 2ATP + 2NADH + 2H+ + 2H20
what are the methods for generating ATP (6)
- Glycolysis
- Kreb’s cycle
- Oxidative phosphorylation
- Substrate level phosphorylation
- Electron transport chain
- Beta oxidation
what does the enzyme kinase do
enzyme that adds/removes phosphate group to things from an ATP
what does the enzyme isomerase do
enzyme that rearranges structure of substrate without changing the molecular formula
what does the enzyme adolase do
enzyme that creates or breaks carbon-carbon bonds
what does the enzyme dehydrogenase do
enzyme that moves hydride ion (H-) to an electron acceptor e.g. (NAD+ of FAD+)
what does the enzyme enolase do
enzyme that produces a carbon=carbon double bond by removing a hydroxyl group
how does ATP provide energy
When the phosphate bonds are
broken energy is released
BUT to ‘break’ bonds an input of energy is required.
As bonds reform in the products of the reaction of the hydrolysis of ATP energy is released.
The energy released making the new bonds is greater than the energy required to hydrolyse the bonds (since they are relatively weak) thus meaning the hydrolysis of ATP gives out energy
what are the regulators of glycolysis and PFK
Adenosine monophosphate (AMP)
Adenosine triphosphate (ATP)
citrate
fructose 2,6 biphosphate
what does Adenosine monophosphate (AMP) regulate
it is an allosteric activator of phosphofructokinase-1 (PFK-1).
it binds to PFK-1 resulting in a conformational change - increasing the affinity of PFK-1 for fructose-6-phosphate
what does Adenosine triphosphate (ATP) regulate
it is an allosteric inhibitor for PFK-1
this means it modifies the active site of
the enzyme so that the affinity for the substrate decreases
at low ATP levels = fast reaction speed of PFK-1 > fructose 1,6 bisphosphate, and at high ATP levels = slow reaction speed of PFK-1 > fructose 1,6 bisphosphate
AMP opposes the allosteric inhibition by ATP
how does citrate regulate glycolysis
it is the first product of the Krebs cycle
acts as an allosteric inhibitor for PFK-1
increased citrate levels is a signal
that the cycle does not need more fuel
how does fructose-2,6-biphosphate regulate glycolysis
it is generated from fructose 6 phosphate
is the most important allosteric activator of PFK 1
it mediates the effect of insulin and glycogen
what is the fate of pyruvate in anaerobic conditions
it is converted to lactate using lactate dehydrogenase
because it cannot enter the Kreb’s cycle or undergo Oxidative Phosphorylation since these processes require oxygen
this leads to regeneration of NAD+
what is the equation for the fate of pyruvate in anaerobic conditions
glucose + 2 ADP + 2 Pi > 2 Lactate + 2 ATP + 2 H2O
what is the fate of pyruvate in aerobic conditions
it enters the mitochondria
is converted to Acetyl CoA and Co2 by pyruvate dehydrogenase - this is an irreversible reaction
Acetyl CoA can enter the TCA cycle for more energy production
what inhibits pyruvate dehydrogenase
high concentrations of acetyl CoA and NADH
what inactivates pyruvate dehydrogenase
phosphorylation
what activates pyruvate dehydrogenase
phosphate removal
what is the equation for the fate of pyruvate in aerobic conditions
pyruvate + CoA + NAD+ ———-> acetyl CoA + CO2 + NADH + H+
catalysed by pyruvate dehydrogenase
what are 2 other names for the Krebs cycle
citric acid cycle
tricarboxylic acid (TCA) cycle
where does the krebs cycle occur
in the mitochondrial matrix
in aerobic conditions
why does krebs need to occur in aerobic conditions
since oxidative phosphorylation is required to covert NADH & FADH2 back to NAD+ and FAD to be used in the conversion of Isocitrate to a-Ketoglutarate and a-Ketoglutarate to Succinyl coenzyme A & Succinate to Fumarate & Malate to Oxaloacetate.
what are the 3 reasons the krebs cycle occurs
1) generates lots of ATP
2) provides final common pathway for oxidation of carbohydrates, fat and protein via acetyl CoA
3) produces intermediates for other metabolic pathways
what are the 3 ways of making acetyl CoA
1) from pyruvate
2) the beta-oxidation of fatty acids
3) from amino acid breakdown
what is acetyl CoA derived from
the B vitamin pantothenic acid
what is the primary function of acetyl CoA
functions primarily to transfer acetyl groups (2 carbons), from one molecule to another.
what is the overall equation for the Krebs cycle
Acetyl CoA + 3NAD+ + FAD + GDP + ADP + Pi + 2H2O > 2CO2 + CoA + 3 NADH + 3H+ + FADH2 + GTP + ATP
give a brief overview of the krebs cycle
acetyl CoA condenses oxaloacetate with acetate
oxaloacetate regenerated in krebs cycle
what are the products of each stage in the krebs cycle
“Can I Keep Selling Socks For Money, Officer ?”
- C - Citrate - Can
- I - Isocitrate - I
- K - a-Ketoglutarate - Keep
- S - Succinyl CoA - Selling
- S - Succinate - Socks
- F- Fumarate - For
- M - Malate - Money
- O - Oxaloacetate - Officer?
what are the regulators of the krebs cycle
- pyruvate dehydrogenase
- citrate synthase
- isocitrate dehydrogenase
- a-ketoglutarate dehydrogenase
what is the role of pyruvate dehydrogenase
converts pyruvate to acetyl CoA
an irreversible and tightly regulated reaction to control how much fuels enters the krebs cycle
what inhibits pyruvate dehydrogenase
ATP and NADH negatively inhibit pyruvate dehydrogenase
acetyl CoA (its product) inhibits it to make sure its only made when its needed
what activates pyruvate dehydrogenase
ADP activates pyruvate dehydrogenase
as well as its substrate pyruvate
what inhibits citrate synthase (4)
ATP and NADH allosterically inhibit citrate synthase
they reduce the affinity of citrate synthase for its substrates
succinyl CoA competitively inhibits citrate synthase
citrate inhibits citrate synthase and increased citrate reduces the speed of the cycle
what activates citrate synthase
ADP
what is isocitrate DH
a key rate-limiting enzyme of Krebs cycle
what causes the rate of krebs cycle to increase
in states of increased oxidative phosphorylation demands
what inhibits isocitrate DH
ATP and NADH
what activates isocitrate DH
ADP
what inhibits a - ketoglutarate DH
its products NADH and succinyl - coA
also inhibited by GTP, ATP and reactive oxygen species (ROS)
what activates a - ketoglutarate DH
Ca2+
may be useful in generating ATP during intense muscle exercise
where does oxidative phosphorylation occur
in the inner mitochondrial membranes
in aerobic conditions
when does oxidative phosphorylation release the majority of energy
during cellular respiration
what happens in oxidative phosphorylation briefly
- reduced NADH or FADH2 from glycolysis and krebs cycle are oxidised
- their electrons are passed to components of electron transport chain (ETC)
- these are a series of carriers embedded in the inner mitochondrial membrane
- the final electron acceptor is O2
- energy released is trapped to generate ATP
what forms the components of the ETC
cytochromes (contain iron and copper co-factors, structure resembles the red iron- congaing haemoglobin) and associated proteins embedded in the inner mitochondrial membrane surface
describe process of oxidative phosphorylation
- Two electrons from hydrogen atoms are initially transferred either from NADH + H+ or FADH2 to one of the protein in the electron transport chain. These electrons are then successively transferred to other compounds in the chain redox reactions, until the electrons are finally transferred to molecular oxygen, which then combines with hydrogen ions (protons) to form water.
- These hydrogen ions, like the electrons, come from free hydrogen ions and the hydrogen-bearing coenzymes (NADH and FADH2), that had been released earlier in the electron transport chain when the electrons from the hydrogen atoms were transferred to the cytochromes.
- IMPORTANTLY in addition to transferring the coenzyme hydrogens to water, this process also regenerates the hydrogen-free forms of the coenzymes (NAD+ & FAD), which can then become available to accept two more hydrogens from intermediates in the Kreb’s cycle, glycolysis or beta-oxidation.
- Thus, the electron transport chain provides the aerobic mechanism for regenerating the hydrogen-free form of the coenzymes
- At certain steps along the electron transport chain, small amounts of energy are released. As electrons are transferred from one protein to another alone the chain, some of the energy released used by the cytochromes to pump hydrogen ions from the matrix into the intermembranal space - the compartment between the inner and outer mitochondrial membranes
- This creates a source of potential energy in the form of a hydrogen-ion- concentration gradient across the membrane.
- Embedded in the inner mitochondrial membrane are enzymes called ATP synthase. This enzyme forms a channel in the membrane, allowing hydrogen ion to flow back into the matrix via chemiosmosis - moving from an area of high concentration of hydrogen ions to an area of low concentration. During this process, the energy of the
concentration gradient is converted into chemical bond energy by ATP synthase, which then catalyses the formation of ATP from ADP and Pi. - The transfer of electrons to oxygen produces on average around 2.5 and 1.5 molecules of ATP for each molecule of NADH + H+ & FADH2 respectively.
