The Krebs Cycle and Oxidative Metabolism Flashcards
where does the Krebs Cycle / The Citric Acid Cycle occur?
what 2 things do we need to start TCA?
what is TCA depedent on?
- Krebs cycle: @ mitochondria
- starting point: Acetyl Co-A & oxaloacetate
- TCA dependent on oxygen presence !
what happens (overview) to acetyl co-A during the TCA?
Acetyl CoA combines with oxaloacetate to form Citrate.
(Citrate is a tricarboxylic acid, hence the name TCA)
This enters the cycle and is progressively oxidised, each time producing NADH/FADH2, until finally forms oxaloacetate again and the cycle can begin again.
Acetyl Co-A is one of the starting molecules needed for TCA. But what is the equation for the formation of Acetyl Co-A from pyruvate?
what is the enzyme used to catalyse this reaction?
what nutrition is needed for this reaction?
- pyruvate + CoA + NAD+ –> acetyl Co-A + Co2 + NADH
- enzyme: pyruvate dehydrogenase (PDH)
- co-enzymes are members of the B-vitamin family. uses TPP (aka vitamin B1)
why is pyruvate dehydrogenase complex (PDH) a pivatol enzyme?
why does PDH need to be regulated?
when is PDH blocked? (2)
pyruvate dehydrogenase is key because it determines whether acetyl Co-A (made from pyruvate) will enter the TCA / Krebs cycle
- PDH needs to be regulated to make sure there is enough ATP for the cell
- PDC is blocked when
a) **levels of Acetyl CoA levels are high
b) ** If reduced NAD levels are high (
- When blood glucose is high, PDC is more or less active?
- When blood glucose is low, PDC is more or less active?
- When blood glucose is high, PDC is more active
- When blood glucose is low, turn down PDC (reducing energy production from glucose)
PDH is regulated in two ways:
- PDH is de/-phosphorylated by which enzymes? what do they add / remove? what is their effect?
which substances control 1.?
:)
- PDH **Kinases inhibit PDH by adding PO4
- PDH PhosphatasesactivatePDHbyremoving**PO4
//
- *control of PDH kinases**
- PDH kinases are activated by ATP, acetyl Co-A and NADH (last two are products of PDH) = switch off PDH.
- Pyruvate & insulin inhibits PDH Kinasese (as pyruvate wants PDH to be active to break pyruvate down) = switch on PDH.
- *control of PDH phosphatases**
- Ca2+ ions activate PDH phosphatises - increases PDH. occurs in muscle -> eventually get more ATP production = switch on PDH
- insulin activates PDH phosphatases - actives PDH
to put simply - insulin has what effect on PDH?
what effect does insulin have of kinases & phosphatases?
what do adrenaline and glucagon do to PDH? - why?
insulin caueses the activation of PDH & eventual production of acetyl co-A
insulin = -ve effect on kinases (which inhibit PDH)
+ve effect on phosphatases (which activate PDH)
adrenaline and glucagon: want pyruvate untouched, so it can be used to make glucose via gluconeogenesis = inhibit PDH
* acetyl co-A is the input for TCA. acetyl co-A can be produced by three ways. What are they? *
1.Glycolysis of glucose to pyruvate
•Converted to acetyl-CoA using pyruvate dehydrogenase complex (PDC)
•Produces 2 reduced NAD molecules per glucose
•1 reduced NAD per pyruvate
2.Transamination of glucogenic amino acids to pyruvate
• Converted to acetyl-CoA using pyruvate dehydrogenase complex (PDC)
3.Beta-oxidation of fatty acids directly to acetyl-CoA
•Produces 1 NADH and 1 FADH2 per acetyl-CoA
so after acetyl Co-A is formed. it feeds into the TCA cycle,
where dose the TCA cycle occur?
(where does the electron transport chain occur - later on but still good to know!)
how many acetly Co-A enter the TCA (from one glucose molecule)
what are the end products of TCA cycle? (3)
- TCA cycle occurs in the mitochondrial matrix
- ETC occurs in the inner membrane of the mitochondria
- acetyl Co-A: 2 molecules made / go into the TCA from only one molecule glucose
- TCA end products:
a) 1 GTP / ATP
b) 3 NADH
c) 1 FADH
BUT BECAUSE HAVE 2 ACETLY CO-As GOING INTO TCA:
a) 2 GTP / ATP
b) 6 NADH
c) 2 FADH
what else can be added to the krebs cycle (apart from acetyl co-A and oxaoloacetate)
intermediates in the krebs cycle can be added from the degradation of amino acids
what are the reduced electron carriers that feed into the ECT from the TCA?
3 NADH + 1FADH2
give overview of ETC :)
where does it occur?
- location: inner membrane of matrix
- reduced co-enzymes NADH & FADH used to create a proton gradient across the inner membrane of the mt
- NADH & FADH offload their H+ to proton complexes
- H+ passes from one complex to another (1->4) in a series of REDOX reactions
- As H+ passes from complex to another in REDOX reactions, the energy produced is sufficient to pump protons from the inner maxtrix, across the inner mt membrane, into the inner membrane space
- this creates a proton gradient. protons can only return to the matrix via ATP synthase -> where ATP is produced
ETC:
what happens at complexes 1-4 ?
@ which complexes are protons from transferred from the matrix to the intermembrane space, making a proton gradient?
- *Complex 1
- ** NADH –> NAD+ + H.
- H+ is transfered to ubiqunione (electron carrier)
- *Complex 2**
- FADH –> FAD + H+
- H+ transfers electrons to ubiqunione
Complex 3
transfers electrons from ubiqunione to cytochrome C
- *4th protein complex
- electrons frocytochrome Ctransferred to 1/2 O2 moleculeis the final electron acceptor from electron transport chain. h20 is produced.**
- protons pumped at complexes 1, 3 & 4 = proton gradient
* why do we need o2 for ETC to occur? *
what happens if we dont have any O2?
- @ 4th protein complex, 1/2 O2 molecule is the final electron acceptor from electron transport chain
- without O2:
- NO ATP Produced
- electrons get stuck on chain. stops the redox reactions = no protons pumped across = no proton gradient = no ATP !
how is ATP produced at end of the ETC?
- protons flow back to matrix through ATP synthase. This drives phosphorylation of ADP:
ATP produced **by oxidative phosphorylation:
ADP + P –> ATP**
in oxidative phosphorylation, one glucose produces how many ATPs?
30-32!
what is uncoupling ?
where does it occur?
- proton gradient is not used in to create ATP
INSTEAD
- proton gradient is used to generate heat (at expense of less ATP produced)
- occurs in brown adipose tissue membrane = thermogenin (aka uncoupling protein)
what is thermogenin?
Thermogenin (called uncoupling protein by its discoverers and now known as uncoupling protein 1, or UCP1)[ is a mitochondrial carrier protein found in brown adipose tissue (BAT). It is used to generate heat by non-shivering thermogenesis
uses proton gradient instead of ATP production
why is cyanide lethal?
cyanide is lethal blocks the terminal cytochrome in ETC= un-coupling production of ATP. DEATH
what controls the TCA cycle? (2)
1. end product inhibition
- *- ATP and NADH** feedback on two dehydrogenase enzymes
- dehydrogenase enzymes activated by Ca2+ to generate more ATP
2. substrate regulation
- cycle depends on the avail. of oxaloacetate, acetyl Co-A and NAD+
important info !
although many organic molecules feed into the TCA cycle, Krebs cycle can also generate other organic molecules such as fatty acids and glucose
the TCA cycle forms a focal point in the network of organic molecules. since many organic compounds feed into the cycle and many also feed out of the cycle
what happens to TCA during hypoxia? why?
- during hypoxia: formation of reactive oxygen species (ROS) -> highly damagin to lipids / proteins / DNA
- oxygen is not there to mop up the electrons at complex 4. electrons are abcked into the ETC
in which ways does the cell respond to hypoxia to try and protec itself? (3)
how does this occur?
protec:
- limit amount of ATP needed
- improve anaerobic production ATP production
- limit ROS to prevent tissue damage
method:
- increased expression of hypoxia induced factors (HIF)
a) HIF is activated -> goes to nucleus = transcription factor.
b) causes expression of genes to allow to survive at low oxygen conditions
Hypoxia induced factors are expressed during period of hypoxia. Name two things that HIF causes to occur in cell?
- reduction in mitochondria (promotes their degredation)
- inhibits the synthesis of new mito. -> less ROS producedd
how does HIF work with cancer? (2)
- HIF works as an oncogene for cnacers bc it allows them to survive at low oxygen.
- HIF1 related to angiogensis, metastasis and poor prognosis
what is Leigh syndrome?
symptoms?
pathology?
Leigh syndrome:
pathology:
- mutations in any of ETC genes = loss of ox. phosphorylation = death of cells dependent on ATP (brain / nerves / muscles)
symptoms:
- death in 2/3 years after birth
- progressive loss of mental abilties and movement
