krebs cycle cycle

4

Biochemistry notes…. After studying biochemistry for two weeks I must say I have developed a love-hate relationship with this subject kind of like with the anatomy.I love learning about the metabolism of carbohydrates, everything makes sense, every puzzle belongs on the right place. But I cannot say the same for enzymes. I just hate haye that part of biochemistry. Learning about enzyme kinetics, alosteric enzymes…. it’s just not fun at all for me. Maybe I haven’t found the method of studyng enzymes. Any suggestions? My biochem exam is in three weeks . So for the next two weeks I will have to learn everything about vitamins, cellular respiration(which hopefully I will finish today), gluconeogenesis, pentose phosphate pathway and everything about the metabolism of lipids. So fantastic?! Am I right? the perks of being a med student

Originally posted by datgifarchive

dragonyoudownwithme said: I signed up to take mine tomorrow morning also T.T

oi yoi yoi… i wish you the best of luck with it!! it’s gonna be grueling but i believe in your abilities friendo!

idk about myself, but in the very least - pack light, bring snacks, have a BIG breakfast, don’t forget your ID, and ARRIVE EARLY!!!

Citric Acid Cycle

The citric acid cycle (sometimes called the Krebs cycle) occurs in the mitochondrial matrix and is the third stage in the aerobic breakdown of glucose. The first, of course, is glycolysis, which creates pyruvate, NADH, and ATP. The second—which isn’t long enough to get its own post—is the linking reaction in which pyruvate is converted to Acetyl CoA. This is a coenzyme that the citric acid cycle breaks down to use later in energy production. Basically, the purpose of the linking reaction is to make pyruvate into something the cycle can use.

The main goal of the citric acid cycle is to convert bond energy (in the form of Acetyl CoA) into its reducing equivalents: i.e., to make some more NADH and FADH2, which are electron carriers. These then go through the electron transport chain and use their electron energy to create ATP. Remember, to reduce a compound is to add electrons to it—think of the mnemonic OILRIG.

So, how does the citric acid cycle do this?

Some diagrams get pretty complicated, especially when you include the enzymes responsible and the carbon compounds formed at every stage, but I’m going to break it into relatively simple steps.

  1. An enzyme joins acetyl-CoA to oxaloacetate in order to form citric acid, which is where the cycle gets its name. Then, a water molecule “attacks” the acetyl, and CoA is ejected from the cycle.
  2. Next, water is ejected and then put back in to help facilitate the reduction of NAD+ into NADH. For every turn of the cycle, 3 NADH molecules are created, and 2 molecules of CO2 are released.
  3. ADP plus a free phosphate group (denoted as “Pi”) is put into the cycle, and these are smushed together to form an ATP.
  4. Finally, FAD+ is reduced to FADH2. (FAD and NAD are both very similar coenzymes, performing the same oxidative and reductive roles in a reaction, but they’re different because they work on different classes of molecules: FAD oxidises carbon-carbon bonds, and NAD oxidises carbon-oxygen bonds)

A diagram might make it a little clearer:

So, let’s do a quick round-up of what’s happened:

  • Acetyl-CoA has been released as two CO2 molecules
  • 3 NAD+ were reduced to 3 NADH
  • 1 FAD+ was reduced to 1 FADH2
  • 1 ADP+Pi formed 1 ATP molecule

This isn’t the end—the main goal of citric acid cycle is to prepare the electron carriers NADH and FADH2 for the electron transport chain, where much more ATP will be made.

Onwards to the ETC!

Further resources: Khan Academy: Krebs Cycle

[AP Bio] TEST FOUR: Cellular Respiration

REGULAR HIGHLIGHTED VERSION CAN BE FOUND HERE

(*IMPORTANT: a lot of the format and diagrams got really messed up on here, I apologize)

cellular respiration = breakdown of fuel to generate ATP for work

3 Key Pathways: 1) glycolysis, 2) citric acid cycle, & 3) oxidative phosphorylation/electron transport chain (ETC)

characteristics: waste products = CO2 & H2O, catabolic pathway

Oxidation-Reduction Reactions

AKA “redox” reactions

-the transfer of electrons
-> can be complete or partial (in cases of covalent bond sharing)

oxidation = the loss of electrons

reduction = the gaining of electrons

“oxidizing” agent = substance that accepts electrons from another

“reducing” agent = substance that gives up/“donates” electrons to another

*the transfer of electrons, as they are pulled down the energy gradient from a molecule of low EN -> molecule of high EN, is exergonic as this transfer causes the electrons to release potential energy

-> can be harvested for work! (INDIRECTLY)

-> cell resp. is all about understanding how the flow of electrons & protons controls the whole process!

Brief Overview of Cell Respiration

Fuel Reactant
Glucose Oxygen
Oxidized Reduced
Reducing Agent Oxidizing Agent
Goodbye electrons! :-c Hello electrons! c-:

oxidized (loses e’s)

C H 0 + 6O  -> 6CO  + 6H 0 + energy (ATP + heat)

reduced (gains e’s)

*typically carbs are used but lipids (fats) can also be used due to the large amount of H’s in the hydrocarbon tails, & actually generate a lot of energy

fun tidbit:
*the metabolic waste, C0 , is breathed out by the body and then taken in by plants, which use it to produce glucose -> thus the circle spins on & on

How Glucose is Broken Down

*energy cannot be efficiently harvested for work all at once, so rather it is broken down in a series of steps, called “stepwise energy harvesting”

1) Electrons taken from glucose (also, 1 proton) are given to Nicotinamide Adenine Dinucelotide (NAD+), a coenzyme
-> NAD+ is an oxidizing agent, and so therefore is able to accept electrons

2) NAD+ is an “empty taxi cab”. The enzyme dehydrogenase oxidizes food (such as glucose) to get the 2 e’s & 2 p’s (H+’s) so they can be given to NAD+.

3) NAD+ is reduced by accepting electrons, and becomes NADH. NADH is a “full taxi cab”, containing 2 e’s & 1 p (H+). The other H+ is released into the cytosol.
-> Each NADH represents potential energy that can be indirectly used to power the synthesis of ATP

4) NADH passes the e’s onto the electron transport chain (ETC). The ETC then passes the e’s on in a series of controlled steps to the oxygen molecules that pull them down the chain (b/c of its high EN). This process yields energy that can be used to re-generate ATP.

Stages of Cellular Respiration

1) Glycolysis- breakdown of glucose (“glyco” = glucose, “lysis” = breakdown)

2) Citric Acid Cycle- completes the breakdown into 2 molecules of pyruvate of glucose (AKA Krebs Cycle)

3) Electron Transport Chain (ETC)- accounts for most of ATP synthesis

 ————————————————————————————————-

(*the following diagram got really messed up on here, I apologize)

electrons carried via
NADH                                                                          electrons carried
                                                                                  via NADH & FADH2

Glycolysis                                                
1 glucose -> 2 pyruvate ——————-> citric acid                                                 (SPLIT)                                                    cycle                    electron transport
                                                                                               and chemiosmosis
                                            
                                                       (mitochondrion)
(cytosol)

                                                                                                         ATPs                                                                              ATP
   ATP

substrate-level                                  substrate-level                                             phosphorylation                                phosphorylation                                                                                                                                                                                                                                                                              *oxidative
                                                                                                phosphorylation*

2 ATPs were invested,                                                       results in a LOT more
and 4 in total produced, so            results in 2 ATPs                       ATPs
NET = 2 ATPs                                    now: total 6
                                                             NET = 4                   produces NET = 32-                                                                                                        34 ATPs                                                                                                                

Glycolysis


-occurs in the cytosol

                        [high] G     outside/ECM

facilitated
diffusion             *Integral protein & cell membrane
(no energy)    
                         [low]  G      inside/cytosol

G-p <— phosphate is added (neg. charge “locks” glucose inside cell!)



-requires the energy investment of 2 ATPs



Energy Investment Phase

1- 2 ATPs invested

2- Enzymes take phosphates off ADPs

3- Series of steps where phosphates are taken off ATPs & then phosphorylated to molecules (TWICE) that are slightly changed each step

4- Eventually split into 2 3-carbon sugars (“G3Ps”)

Energy Yielding Phase


1- As the 2 G3Ps are oxidized, NAD+ is reduced to NADH -> this contributes to the ETC by carrying electrons (& protons)!

2- After, there is an “intermediate molecule” (ex: 1,3-biphosphoglycerate -> don’t need to know exact molecule) that has a phosphate. This phosphate is taken off and given to 2 ADPs to become 2 ATPs. This happens twice within the series of steps in this phase. Also, at one point, 2 H2Os are taken out.

3- Eventually transformed into 2 pyruvates

4- A total of 4 ATPs are made in this “payoff” phase. However, since 2 were invested originally, there is only a net of  2 ATPs.

                                      C3H3O3
C6H1206                    -pyruvates-
                                      C3H3O3

(*this diagram got really messed up on here too)

Energy Investment Phase



Glucose



2 ADP + 2 p <—————— 2 ATP used



Energy Payoff


Phase      4 ADP +


                    4 p          ———————->   4 ATP    formed



2 NAD+ + 4 e


+ 4 H+                   —————————>   2 NADH + 2 H+



                 


                                                    ————–> 2 Pyruvate + 2 H2O




Net                     Glucose ————> 2 Pyruvate + 2 H2O



4 ATP formed - 2 ATP used ——-> 2 ATP



2 NAD+ + 4 e + H + ———-> 2 NADH + 2 H+




Substrate-Level Phosphorylation

-not as efficient in producing ATP as oxidative phosphorylation

-used in both glycolysis & krebs/citric acid cycle

Citric Acid Cycle

-AKA “Krebs” Cycle

-COMPLETES energy-yielding oxidation of the organic molecules (ex: glucose)

-BEFORE the cycle can begin, the 2 Pyruvates must be converted to Acetyl CoA -> this links the cycle to glycolysis!

1) The 2 Pyruvates are oxidized and enter the Mitochondrion via a Transport Protein

2) CO2 is released (lungs -> exhale)

3) NAD+ is reduced to NADH & the e’s & p’s (H+’s) are stripped

4) A Coenzyme helps with the conversion to Acetyl CoA

-CAC uses BOTH molecules of pyruvate
*cycle goes around TWICE!

*CITRIC ACID CYCLE SUMMARY*

2 CO2 X 2 = 4 (released)

3 NADH X 2 = 6 (reduced)

1 FADH X 2 = 2 (reduced)

1 ATP X 2 = 2 (produced)

*appreciate the many redox Rx’s going on to keep the cycle going, changing Acetyl CoA all the way to Oxaloacetate!

Ex: R = NAD+ -> NADH
     O = any previous molecule!

ETC - Chemiosmosis - Oxidative Phosphorylation

-located at the inner mitochondrial membrane (like the plasma membrane, but different proteins!)                                                                              

*proteins are special ones made from the mtDNA (mitochondrial DNA)

*2 membranes! (DOUBLE)

PROTON MOTIVE FORCE

-facilitated diffusion

-a lot of energy & collisions b/c of flow of e’s

-*H’s come from glucose/pyruvate!

1) H+’s pumped out
2) O’s take H+’s to create H2O
3) Take protons in -> [low] guaranteed

-energy to power movement of H+ out!
(POTENTIAL ENERGY -> from redox Rx’s!)

-if O2 NOT present, H+’s cannot be moved/slid out -> b/c O2 is the final e acceptor w/ a high EN & the e’s release potential energy when moving down the gradient to O which powers the proton motive force

-keeps getting more EN as e’s pulled down/along chain

-H+’s move into ATP Synthase (important and moves protons BACK into matrix) protein -> active transport -> change of shape -> ATPs

fun tidbit:
-cyanide affects the enzyme that works w/ cytochrome oxidase, as it is an irreversible inhibitor that is tetravalent and desperate for a fourth bond, and therefore highly reactive (can shut down body systems and kill you within a matter of hours, and this is all due to bonding!)

ELECTRON TRANSPORT CHAIN

-oxidative phosphorylation & chemiosmosis couples the ETC to ATP synthesis

-located in cristae of mitochondrion

Pathway:

1) The components are proteins that exist in multiprotein complexes and are unique to the mitochondrion. These protein complexes alternate between reduced and oxidized states as they accept and donate electrons

2) Electrons drop in free energy as they go down the chain & are finally passed to O2 -> form H2O

3) NO ATP generated!!!!!

*THE FUNCTION OF THE ETC is to break the large free-energy drops from food to O2 into smaller steps that release energy in manageable amounts.

*the more redox Rx’s, the more energy is available.



CHEMIOSMOSIS

*the energy-coupling mechanism

1) Redox Rx’s in the ETC -> provide energy for the transport proteins to pump H+ from the mitochondrial matrix to the intermembrane space.

NEXT STEP IMMEDIATELY FOLLOWS

2) Proton Motive Force  develops as [H+] INC., w/i intermembrane space. Then, moves back across membrane & passes through channels in ATP Synthase.

3) ATP Synthase transports H+ BACK into matrix.

4) ATP Synthase uses exergonic flow of H+ to drive the phosphorylation of ADP -> ATP    (endergonic).

*chemiosmosis = use of energy in H+ chemical gradient to drive ADP phosphorylation

Fermentation

*enables some cells to produce ATP w/o the use of oxygen!

How can food be oxidized w/o oxygen?

-NAD+ is actually the oxidizing agent of glucose. A net of 2 ATPs are produced by substrate-level phosphorylation. Then, if there IS oxygen, more (a lot of) ATP can be produced when NADH passes the removed e’s from glucose to the ETC & oxidative phosphorylation occurs.

*glycolysis STILL produces 2 ATP whether O is present of not, though!

(either aerobic or anaerobic)


-fermentation is the anaerobic catabolism of nutrients

-fermentation = the extension of glycolysis that can generate ATP solely by substrate-level phosphorylation
-> *as long as there is a sufficient supply of NAD+ to accept e’s during the oxidation step of glycolysis

-NAD+ needs to be recycled from NADH

Aerobic Anaerobic
Recycled by the transfer Recycled by the transfer of electrons from NADH to Pyruvate (end product of glycolysis!)
of electrons to the ETC

TYPES OF FERMENTATION

fermentation = glycolysis + Rx’s that regenerate NAD+ (transfer of electrons from NADH -> Pyruvate)

Alcohol Fermentation = Pyruvate converted to Ethanol

1) RELEASES CO2 from Pyruvate
-> converted to 2-carbon compound “acetaldehyde”

2) Acetaldehyde is reduced by NADH to Ethanol

-regenerate supply of NAD+ needed

*many bacteria carry out alcohol fermentation under anaerobic conditions, also fungi (ex: yeast)

fun tidbit:

yeast -> used for 1,000’s of years by humans for brewing, wine-making, baking (bread, gases released create bubbles that allow it to rise), etc.

Lactic Acid Fermentation = Pyruvate reduced DIRECTLY by NADH - > forms Lactate (ionized form of lactic acid) as end product -> NO release of CO2

*certain fungi & bacteria used to make cheese & yogurt

*other microbial fermentation used to make acetone & methanol (methyl alcohol)

1) When O is scarce, human muscle cells can still make ATP by using lactic acid fermentation.

2) Strenuous exercise -> sugar catabolism for ATP production outpaces muscle’s supply of O from blood

3) Cells switch from aerobic respiration to fermentation -> creates lactate -> buildup of lactate can cause muscle fatigue and pain!

4) Lactate is gradually carried away by the blood to the liver -> converted back to pyruvate by liver cells

*facultative anaerobes = make enough ATP to survive using either fermentation or respiration (ex: our muscle cells!)
-> consume sugar at faster rate when fermenting to make the same amount

*Pyruvate is a “FORK IN THE ROAD”

thelastgambit-deactivated201404  asked:

Currently learning about glycolysis/Krebs cycle. After the Krebs cycle, NADH and FADH facilitate the creation of electrochemical gradients across cell membranes, but I don't understand how the electrochemical gradient helps with synthesis of ATP. I understand the basics (i.e. H-plus moves through the protein ATP-synthase, which kickstarts bulk ATP production), but is there a resource somewhere that can explain it to me in more detail?

Crash course on Glycolysis

Goofy/weird Macklemore dub of Krebs cycle

Color Coding Bio Notes

I’m pretty sure some Bio majors are either already doing this

But here is some brands that I would recommend

(I like to get the sets that come in various colors - Note: Sharpies, Gel Pens, and pens like Sakura Microns are not the best to use while taking notes because they either feather out or bleed through Note book paper

This also applies to the STABILO markers and pens in this pic above - Those are great for diagrams

(though on printer/notebook paper they sometimes bleed through)

Paper Mate: Ink Joy pens are smooth and great to take notes with (and draw with too!)

I hope this was helpful in some way.