Krebs Cycle & ETC Flashcards
What is the krebs cycle? Where in the cell does it occur
Central pathway in catabolism of sugars, fatty acids, ketone bodies, amino acids, alchohol.
Mitochondria
How many atp does the kreb cycle produce per molecule of glucose?
32
What activates the kreb cycle to work?
low energy signal loke ADP ( this occurs during muscle comtraction when atp gets low and adp increases)
______cycles for every on emolecule of glucose in the krebs cycle
2
What r the products of the krebs cycle
-6NADH -2 FADH2 -2GTP
Does krebs cycle need oxygen to work
Yes, or itll stop
After weve created NADH AND FADH2 from the krebs cycle, where does this energy go now?
To the inner mitochondrial matrix to drive the electron transport chain,
PDH deficiency causes….
Lactic acidosis
Give examples of high energy status that inhibit the krebs cycle
Acetly Coa
NADH
ATP
CITRATE
Phosphorylation
How is citrate (6-carbon) formed in the krebs cycle?
Acetyl Coa (2C) binds with oxaloacetate (c4) to form CITRATE (c6)
What happens to acetly Coa as it is going through the krebs cycle?
They lose their 2 heads (co2) as well as their money (NADH)
After we gotton NADH and FADH2 from the krebs cycle…where do these go?
To the electron transport chain in the inner mitochondrial matrix
Explain the process of NADH & FADH2 once they reach the ETC
They unload their electrons on the “proton transport complexes” and this releases energy and passes H ions out into the mitochondria inter membrane space.
What has this unloading of electrons in the complexes result in (2)
- creates a gradient of H ions across the inner mitoch. membrane
- creates an electrical gradient as well ,this causes the H ions to want to renter the matrix as well
(2forces acting against each other)
How does H+ ions renter the mitochondrial matrix since they r impearmeable?
Via the ATP synthase, Uses ADP & pi to make ATP and drives H+ back inside the matrix
What does the atp synthase do?
-makes Atp -brings back H back inside the matrix
Which one has more energy? FAD or NAD
electrons in NADH has more energy and uses all 3 proton conplexes while FADH2 uses 2
What determines when the Oxidative phosphorylation in ETC works? Or stops?
Availability of ATP, alot of ATP will hault it (theres enough)
How is oxidative phosphorylation regulated?
Hight ATP=Low ADP
What r types of toxins that inhibits oxidative phosphorylation?
Cyanide, inhibits cytocrome C in complex 4!
CO
What do uncouplers do to the ETC?
They increase the permeability of H to the membrane,
What is meant by the proton motif force? PMF
Electronchemical potential diff. Of protons
**THE GREATER THE PMF THE MORE ATP SYNTHESIZED
reminder
The conversion on pyruvate to Acetly CoA, is that reversable? Or irreversible? & why?
It is irreversible, bc there is a loss of Co2
What disorder do u get if u have PDH defiencinecy
Lactic Acidosis
A 22 year old female was admitted to hospital after being found unconcious. Her body temperature was 42 oC. Upon further investigation it was found that she had taken 6 slimming pills that morning which she had purchased from the internet. These slimming pills contained dinitrophenol (DNP), an uncoupler of oxidative phosphorylation.
What would be the effect of dinitrophenol on oxidative phosphorylation?
DNP acts as a protonophore,
allows H+ to leak across the inner mitochondrial membrane and ignore the ATP synthase.
instead of being converted to ATP, the energy from the ETC is released as heat (which explains her body temperature).
Note that a similar physiological mechanism also occurs in the brown adipose tissue of infants facilitated by uncoupling proteins such as thermogenin (UCP1) in order to generate heat.
What effect does the poison cyanide have on the ETC?
Cyanide prevents the flow of electrons through the electron transport chain.
inhibits the enzyme cytochrome c oxidase, (Complex IV in the electron transport chain).
Since complex 4 is no longer able to facilitate the acceptance of electrons by O2,
The ETC stops and the PMF driving ATP synthesis fails.
Alaa, It is important that you understand the distinction between the mechanism of action of inhibitors of the electron transport chain such as cyanide & uncoupling agents such as dinitrophenol.
With uncouplers electron transport continues but with heat production rather than ATP production
with inhibitors both the transport of electrons and ATP production stop.
Oxidative phosphorylation utilises a proton gradient to synthesise ATP
Reminder
which molecule combines with acetyl coA to form citrate in the 1st step of the krebs cycle?
oxaloacetate
what is the energy producing role of the krebs cycle?
to produce NADH & FAD2H to supply the ETC with high energy electrons
which stage in metabolism produces the most energy in the form of ATP?
ETC
what is the function of the 2 lipid bilayers in the mitochondria
allows maintenance of a proton gradient needed for Oxidative-phosphorylation
what r the uncouplers of the Oxidative-phophorylation? (2) what r their mechanisms of inhibition
dinitrohenol, fatty acids,
-increase permeability of inner membrane to H, & H enters the mitochondria 3ala waif uma w/ out using the ATP synthase, PMF is lost,
ETC KEEPS GOING, ATP DOES NOT FORM and EXCESSIVE HEAT IS FORMED!
brown adipose tissue contain thermogenic (UCP1), what is this and what is its significance?
naturally-occurring uncoupling protein, normally inactive.
activated by fatty acids
- Transports H+ back into mitochondria without driving ATP synthesis > ETC is uncoupled from ATP synthesis, and energy of pmf is released as extra heat instead of ATP.
- involved in non shimmering thermogenesis, which enables mammals to survive cold environments.
where is brown adipose tissue found
in infants & hybernating animals
role of uncoupling proteins UCP in ETC
uncouples the ETC from ATP production to produce heat
how is kerbs cycle regulated?
rate of ATP utilisation.
how is ETC and ATP sythesis coupled
they’re so tightly coupled, that one does not occur with out the other.
how and when and why does uncoupling of the ETC occur?
.
compare oxidative phosphorylation and substrate level phosphorylation
what is the ‘pmf’ in ETC?
complexes in etc transform the chemical bond energy into an electro-chemical potential difference of protons
does ETC need oxygen to work?
yes
how can protons in the etc renter the mitochondrial matrix?
via the ATP synthase
**the greater the pmt, the more Atp is made
just saying
what plays an important role in regulating both the processes { ETC & ATP synthesis}? explain
mitochnodrial concentration of ATP. if ATP is high ADP is low, and the ATP synthase stops.
what is crp?
acute phase protein raised during an inflammatory response
Acetyl coa can somtimes be needed for fatty acid synthesis, describe the process
Acetyl coa cannot leave mitochondira, instead CITRATE will leave into the cytosol & there it will release its ocaloacetate component and binds w/ Coa to form acetyl coa
In times of burst activites, where does the body get its energy from?
Phosphocreatine store
A temporary energy store, that releases energy during emergency or quick times! Like a burst of activity
for ex, it does this my removing the phosphate,>>>ATP can then be regenerated by the reverse reaction when its concentration falls.
Creatine phosphate can thus act as a small store of free energy in muscle cells (skeletal and cardiac).
**This store is important in the first few seconds of vigorous muscle activity such as sprinting.
What is the function of creatinine?
Creatine and creatine phosphate both undergo changes producing creatinine.
Creatinine has no function in the body! excreted via the kidneys in the urine.
The rate of production of creatinine is proportional to the concentration of creatine in muscle! and this is related to skeletal muscle mass.
The daily excretion of creatinine can be used as an INDICATOR of skeletal muscle mass –>increased excretion of creatinine may indicate active muscle wasting!!
U check the creatinine of a pateient and it is reltively high, What can this mean & why
Either There is obvious muscle wasting in the body. OR indicator of kidney function since the kidney is normally very efficient at removing creatinine from the blood. ** high blood creatinine with low urinary creatinine concentration may indicate reduced kidney funtion
where is the final destination for an electron in the ETC?
goes to the oxygen molecule along with protons combined to form WATER
in which condition would u see heinz bodies?
G6PDH defeiciency!
functions of the TCA cycle
The TCA cycle has both catabolic and anabolic roles.
catabolic role>> oxidise the acetyl group of acetyl~CoA to two molecules of CO2, with the reduction of NAD & FADH and formation of GTP. The NADH and FADH2 are subsequently oxidised via the respiratory chain to generate ATP by oxidative phosphorylation.
anabolic role >>provide intermediates for the synthesis of various important molecules such as haem, fatty acids, glutamate and aspartate
The TCA cycle plays also an important role in the conversion of several glucogenic amino acids to glucose.
what r ketone bodies? where r they made? what does the synthesis of ketone bodies require?
List the three ketone bodies produced in humans and explain why they are only produced under certain conditions
Acetoacetate - Acetone- β-hydroxybutyrate.
Ketone bodies are important fuel molecules that can be used by all tissues containing mitochondria. including the CNS.
The rate of utilisation is proportional to the plasma concentration.
They are converted to acetyl~CoA and this is oxidised.
Ketone bodies are synthesised in liver mitochondria from acetyl~CoA >>> (HMG CoA)>>>acetoacetate by a lyase enzyme.
acetoacetate then goes to make the other 2 ketone bodies!
- (The activity of the lyase enzyme is controlled by the insulin/glucagon ratio. When the ratio falls, the lyase is activated and when the ratio increases, the lyase is inhibited. )*
- The synthesis of ketone bodies requires both of the following:*
1) Fatty acids available for oxidation in the liver following excessive lipolysis in adipose tissue.
2) The plasma insulin/glucagon ratio to be low, usually due to a fall in plasma insulin.
These two conditions are only normally met in starvation. However, they can occur in untreated type 1 diabetes producing ketoacidosis.
describe the metabolism of paracetamol, where does it occur? what can an overdose do? how can we treat it
in HEPATOCYTE, it is safely metabolised by conjugation with -Glucuronide -Sulphate
OVERDOSE@#$#%$@
we start to get production of this TOXIC metabolite called ‘NAPQI’ (toxic nappy)
1) direct toxic effects on the liver -damage to dna -damage to proteins -lipid peroxidation
2) conjugate w/ GLUTATHIONE —–> depleting the glutathione stores in the liver, leaving it more prone to oxidative stress!
Give antidote Acetylcystine! works by restoring gluthione levels!
how can u treat overdose of paracetamol? why should u act FAST?
Because effects r IRREVERSIBLE give antidote ACETYLCYSTINE w/ in 8HRS!
-works by restoring glutathione levels SOOO.. Acetylcysteine serves as a prodrug to ‘L-cysteine.’ it’ll act as a PRECURSOR for more glutathione to be made.
(remember glutathione is a tripeptide! Glycine-Cys-Glutamate)
Which glucose transporter is a bi-directional transporter expressed in liver?
GLUT 2
one NADH produces______ATP
one FADH produces______ATP
3 atp
2atp
role of PDH pyruvate dehydrogenease
it needs vitamen_____to work
what does this vitamen do?
PDH is a large multi-enzyme complex (5 enzymes)
converts
pyruvate ——->Acetyl Coa
The different enzyme activities require various cofactors (FAD, thiamine pyrophosphate and lipoic acid).
B-vitamins provide these cofactors, so reaction is sensitive to Vitamin B1 deficiency. !!!
*
what causes the smell of _____is smelt in the breath of an untreated type 1 diabetic!
Acetone!
The synthesis of ketone bodies requires both of the following (2)
1) Fatty acids available for oxidation in the liver following excessive lipolysis in adipose tissue.
2) The plasma insulin/glucagon ratio to be low, usually due to a fall in plasma insulin.
Label this According to the fed/starved state
what r ketone bodies? explain how the r formed in the body? exaplin the fate of all 3
-water soluble molecules> a property that allows high plasma concentrations and their excretion from urine. (ketonuria)
Acetoacetate & B hydroxybutrate > formed form Acetyl CoA
Acetone arises from random decarboxylation of Acetoacetae.
- Acetoacetate & B hydroxybutrate>>r strong organic acids> if high in plasma>ketoacidosis
- Acetone> volatile (easily evaporated)>> excreted via lungs!
