EK B1 Ch3 Metabolism I Flashcards
phosphate groups on ATP
very hydrophilic donation of these groups can change conformation of proteins - phosphate groups of ATP contain phosphoanhydride bonds or phosphoric acids*** that are linked to an oxygen atom, reactivity is very similar to anhydrides
phosphoanhyride bonds
- hydrolysis is exothermic and spontaneous, can provide energy required for less energetically favorable reactions
delta H
change in enthalpy -negative for exothermic reactions
enthalpy is the heat that is gained or lost in a reaction
spontaneous reactions
delta G, change in Gibbs free energy is negative NOTE atp –> adp + Pi (gamma phosphate) has delta G <<<0 SO SPONANTEOUS AND NEGATIVE
oxidative phosphorlyation
occurs when oxidation reactions provide the energy for phosphorylation
-requires the presence of oxygen as a final electron acceptor
- in mitochodnria for ETC
- energy comes from NADH, which is reduced form of nicotinamide adenine dinucleotide NAD+
substrate level phosphorylation
oxidation and phosphorylation are not coupled! ADP is simply one of several substrates in an enzyme-catalyzed reaction that results in transfer of a phosphate group to ADP - there are enzymes in both glycolysis and the citric acid cycle that catalyze substrate level phosphorylation
phosphorlyation
ATP is synthesized by teh addition of a phosphate group to adenosine diphosphate
acteyl-coa
coenzyme that transfres two carbons from pryvuate to 4-carbon oxaloacetic acid to begin the citric acid cycle (also known as Krebs cycle or TCA tricarboxylic acid cycle –> during this cycle two carbons are lost as CO2 and oxaloacetic acid is regernated
Each citric acid cycle….
-1 ATP, 3 NADH, 1 FADH2 - one GTP is converted to ATP via substrate level phosphorlation and 2 CO2** -one glucose model powers two turns of cycle, so really its 6 NADH, 2 ATP, 2 FADH2 only 2 NADH made per two glucose in glycolysis
beta- oxidation
produces 1 nadh per two carbon versus 3 NADH in TCA/KREBS/ ctric acid cycle
GTP in citric acid cycle
acts as phosphate donor to ADP to produce ATP, this process occurs via substrate level phosphorlyation just like glycolysis
what step exactly does GTP come in? so can draw on diagram for a blink of an eye, substrate level technically produces GTP then convert to atp
occurs between succinly-CoA using to succinate, enzyme succinyl-Coa synthetase converts it to succinate produces ATP and CoA-SH
so technically GTP subtrate level phosphorylation, adp + pi goes to GTP and quickly gtp converted to ATP!
NAD+ in TCA
regulation of TCA is tied to amount of NAD+ available, it is generated by the oxidation of NADH by the electron transport chain. If the ETC is inhibited, as when there is a lack of oxygen, NADH cannot be oxidized to NAD+. - in this case TCA is inhibited and the cell shifts its energy to anerobic respiration/pathways as a result TCA considered to be aerobic
NADH regulation in TCA
-citric acid cycle produces NADH! so if an excess of NADH builds up, the reactions slow down!
metabolism fats and proteins into TCA
-Acetyl-Coa not only substrate that can enter the TCA -some molecules can be modified to various TCA intermediates that can enter the cycle -amino acids come with carbon backbone, denamiated in liver -the deanimated product may be chemically converted to pyruvic acid or acetyl coa or it may enter TCA at various stages depending upon length of the carbon backbone
glutamic acid
5 c backbone can be converted into citric acid cycle intermediate alpha-ketoglutarate
to be used for energy.. amino acids
- must first be deanimated, after which they can enter the TCA as pyruvate or as one of the TCA intermediates -fats are converted to acetyl-CoA which can then enter the citric acid cycle, NUCLEOTIDES ARE NOT DENANIMATED!
ETC (NADH)
NADH loses electrons, is oxidized to become NAD+ - oxygen gains electrons, is reduced to form water!
atp synthase
ex of oxidative phosphorylation
type 1 diabetes
- autoimmune disease where the immune system attacks the beta cells of the pancreas
glucogenoesis
Blueprint exam 4 details
Gluconeogenesis is a process that the body uses to create glucose from pyruvate. It occurs primarily in the liver and to some extent in the adrenal cortex, and its goal is to ensure an adequate supply of glucose (which can then be converted into energy, or stored as glycogen) throughout the tissues of the body. In particular, it can be important to replenish the stores of glycogen in muscle cells after they have been depleted by intense activity. It is upregulated by glucagon and by the presence of surplus pyruvate/acetyl-CoA.
Gluconeogenesis is not quite reverse glycolysis, although these two pathways do share some of the same enzymes and steps (although they occur in reverse). However, they also differ at some crucial stages. Glycolysis contains some steps that are highly exergonic and essentially irreversible under biological conditions, so gluconeogenesis needs to bypass those steps. Additionally, glycolysis and gluconeogenesis need to be separated in order to prevent a futile cycle in which glucose is broken down to pyruvate and then pyruvate is built back up into glucose.
Gluconeogenesis
Blueprint Exam 4 concept cont.
In particular, the final stage of glycolysis (phosphoenolpyruvate [PEP] → pyruvate) must be bypassed by gluconeogenesis.
Thus, why gluconeogenesis has a two-step pathway split up between the mitochondria and cytosol, in which pyruvate carboxylase converts pyruvate to oxaloacetate in the mitochondria by adding a COO- group.
Oxaloacetate is briefly converted to malate for transport out of the mitochondria, where it is then converted immediately back to oxaloacetate. At this point, in the cytosol, PEP carboxykinase converts oxaloacetate to PEP.
Additionally, the early stages of glycolysis (where phosphate groups are added to glucose) must be bypassed by gluconeogenesis. These are irreversible steps in glycolysis that involve the investment of ATP. Gluconeogenesis cannot simply reverse these steps, because doing so would mean creating ATP, which is the job of ATP synthase in the electron transport chain. Instead, gluconeogenesis bypasses these steps using enzymes that catalyze a simple hydrolysis reaction, splitting off a Pi from the carbohydrate.
breaking down fats….
Cause and effect:
- breaking down fats produces glycerol which can enter gluconeogenesis as DHAP
- proteins can break down into glucogenic amino acids which can enter gluconeogenesis as OAA, which is then converted to PEP by PEPCK
Q13 Blue print
Which specific class of enzymes is primarily responsible for the release of free glycerol from stored triglycerides?
- Lipase
Every enzyme you will ever see on the MCAT will fit under one of these labels. The test makers will not expect you to learn a bunch of random enzymes, but they will expect you to match an enzyme’s name to the clues given about its function, or vice versa. Luckily, most enzymes are named for exactly what they do (e.g., pyruvate decarboxylase) and for the substrate they act upon (e.g., DNA ligase).
Typically, only 10-15% of an individual’s energy comes from the metabolism of protein. A woman has a disorder that causes her body to preferentially degrade protein, leading her to obtain 85% of her energy from protein metabolism. What is a potential symptom of this disease?
A.Ketoacidosis
B.Organ failure
C. Low blood sugar
D.Decreased fat stores
A.
Ketoacidosis
Ketoacidosis is caused by an excess of ketone bodies, which are generated from the oxidation of fatty acids, not proteins.
B.
Organ failure
B is correct. If an individual were using proteins as her primary fuel, she would quickly run down her muscular protein stores and would be forced to degrade proteins from organs. This would cause organ failure. Under starvation conditions, muscular atrophy can be observed when both sugar and fat supplies have been depleted.
C.
Low blood sugar
If the body is burning proteins instead of sugar, if anything, hyperglycemia would result.
D.
Decreased fat stores
Fat stores should not become smaller because this individual is not drawing her energy from fat.
A. The solid line is ketone bodies, while the dashed line is fatty acids.
B.The solid line is glycogen, while the dashed line is glucose.
C.The solid line is ketone bodies, while the dashed line is glucose.
D.The solid line is insulin, while the dashed line is fatty acids.
The solid line is ketone bodies, while the dashed line is fatty acids.
This answer is incorrect
B.
The solid line is glycogen, while the dashed line is glucose.
This answer is incorrect
C.
The solid line is ketone bodies, while the dashed line is glucose.
C is correct. During starvation, as glucose (dashed line) supplies decline, fatty acid oxidation and ketone body (solid line) synthesis will take over to supply metabolic fuel.
D.
The solid line is insulin, while the dashed line is fatty acids.
This answer is incorrect
catabolic rxns
- Metabolism consists of two classes of chemical reactions: catabolic and anabolic
- Catabolic reactions break down larger molecules and release energy (exergonic)
anabolic rxns
Anabolic reactions build up from smaller molecules and require energy (endergonic)
Metabolic rxns are catabolic and anabolic…..
Reactions are often coupled to drive anabolic reactions
ATP is the short term energy currency in the cell
ATP hydrolysis yields ADP + Pi , –7.6 kcal/mol energy
Humans and other animals are heterotrophs: must consume energy from outside sources
Plants are autotrophs: make their own food via photosynthesis
ATP hydrolysis yields ………
ATP hydrolysis yields ADP + Pi , –7.6 kcal/mol energy
Metabolic- redox reactions….
Redox reactions transfer energy through electron transfer
Reduction and oxidation always occurs together
Reducing agent causes something else to be reduced. It is oxidized
Oxidizing agent causes something else to be oxidized. It is reduced
Redox is critical for cellular respiration
Reduction in Metabolism
Reduction is a gain of electrons (valence # is reduced, e.g., Fe3+ to Fe2+, NAD+ to NADH)
A reduced molecule gains energy when it gains an electron
Reduction often takes the form of hydride addition (H– = H+ + 2e)
NADH and FADH2 act as hydride donors (much like NaBH4 and LiAlH4 in orgo)
Oxidation in Metabolism
Oxidation is a loss of electrons (valence # is increased, e.g., NADH to NAD+)
An oxidized molecule loses energy when it loses an electron
Oxidation often means more bonds to oxygen
Examples: addition of –OH groups or conversion of C-O single bond to C=O bond
Free energy
Free energy, ∆G, represents energy available to do work
∆Go = free energy change under “standard conditions”
Standard conditions = 25°C, 1 atm pressure, all solutions at concentration of 1M
These conditions are rarely met in real situations
Equilibrium constants reported in tables usually depend on ΔGo
They show whether products or reactants are favored when both start at 1M (unlikely)
ΔG = actual free energy change
ΔG= ΔG° + RT lnQ
ΔG =
ΔG = actual free energy change
ΔG°’=
ΔG°’= free energy change under standard cellular conditions
∆Go =
∆Go = free energy change under “standard conditions”
standard cell conditions
Standard cellular conditions = [H+] = 1 × 10^–7, all other aq concentrations = 1M
ΔG’= free energy change under actual cellular conditions
Typical temperature in human cells = 37°C
Typical concs = 1–4mM ATP, 0.1–1mM ADP, 1–3mM inorganic P, 0.2–1 mM Mg2+
These concentrations influence actual free energy of ATP hydrolysis
Aerobic respirations
Glucose C6H12O6 + 6 O2 → 6 CO2 + 6 H2O + energy (in form of ATP)
Glucose is oxidized, oxygen is reduced
ATP is formed by two mechanisms
Substrate-level phosphorylation: phosphate transferred directly from substrate to ADP
Oxidative phosphorylation: ATP made from energy stored in NADH, FADH2
Most energy during respiration comes from oxidative phosphorylation
Stage 1. Glycolysis
Stage 2. Formation of acetyl coenzyme A
Stage 3. Citric acid cycle (also called Krebs cycle or tricarboxylic acid cycle (TCA))
Stage 4. Electron transport chain
Substrate-level phosphorylation:
= phosphate transferred directly from substrate to ADP
Oxidative phosphorylation
ATP made from energy stored in NADH, FADH2
glycolysis
Glycolysis takes place in the cytoplasm
Glycolysis (sugar-splitting) is the breaking of glucose into 2 pyruvate
Highly conserved across kingdoms
2 ATP used for glucose and fructose phosphorylation
4 ATP produced by substrate-level phosphorylation
4 ATP out – 2 ATP in = 2 ATP net
Glucose enters cell, often by co-transport with sodium
First half of glycolysis = energy investment
Step 1 Glycolysis
Step 1: glucose is phosphorylated to glucose-6-phosphate by hexokinase
- ATP is the source of the phosphate group
- Glucose is trapped in the cell. Could go on through glycolysis or be stored as glycogen
- Hexokinase is in most cells, including muscle and brain
- Hexokinase has low Km (high affinity for glucose) but low Vmax
- Hexokinase will work even when glucose levels are low
- Glucokinase is an isoform of hexokinase that works mainly in liver and pancreas
- Glucokinase has high Km (low affinity for glucose) and high Vmax
- Clears excess glucose after meals, avoiding hyperglycemia
NEGATIVE DELTA G sponateous!
step 2 glycolysis
Step 2: glucose-6-phosphate is isomerized to fructose-6-phosphate
Enzyme is an isomerase
Step 3 glycolysis
Step 3: fructose-6-phosphate is phosphorylated to fructose 1,6-bisphosphate
ATP is the source of the phosphate group
Enzyme is phosphofructokinase. This is the committed step of glycolysis = first irreversible step unique to glycolysis
Phosphofructokinase allosterically inhibited and activated
Inhibition by high ATP or citrate
Activation by high AMP or ADP
Reaction is highly exergonic, essentially irreversible
Note that molecule is becoming more symmetrical before splitting occurs
\step overal is negative delta g has to couple those two parts of what is going on, every step has to be negative delta G overall otherwise it will not happen that is what makes it spontaneous, PEP going to pyruvate if just isolating creating of atp that requires energy input but so much energy is released when PEP get to pyruvate that compensates negative delta, every step is negative delta G very thing has to be favorable and negative delta G, exergonic
so reverse can be favorable adn exergonic, if you had to precisely reverse, like hexokirnase all of that would be unfavorable positive delta G in the reverse direction so in order to make that step and the glconeogenesis step process it gets done in a different way,
OVERALL ALL NEGATIVE delta G
bc using atp up
Step 4 of glycolysis
Step 4: fructose 1,6-bisphosphate is cleaved
Enzyme is aldolase (reverse aldol reaction)
Products = dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P)
Steph 5 glycolysis
Step 5: DHAP is converted to G3P. Only G3P continues on through glycolysis
Second half of glycolysis = energy pay-off
Now step 6
Step 6 glycolysis
Step 6: G3P is converted to 1,3 BPG, a high-energy compound
This involves phosphorylation and oxidation. NAD+ is reduced to NADH
This step is endergonic
1,3-BPG is a special high-energy compound that can be used to make ATP
step 7 glycolysis
Step 7: 1,3-BPG transfers a phosphate group to ADP to make ATP
The product is 3-phosphoglycerate (3PG)
This is substrate-level phosphorylation
Steps 6 and 7 are coupled. Together they are exergonic
step 8 of glycolysis
Step 8: 3PG is converted to 2PG (phosphate group on carbon 2 instead of carbon 3)
• The enzyme is a mutase.
- Mutases catalyze internal transfers of phosphate groups
Step 9 of glycolysis
Step 9: 2PG is converted to phosphoenolpyruvate (PEP), a high-energy compound
Enzyme is an enolase
PEP is a high-energy phosphate compound that can be used to make ATP
\step overal is negative delta g has to couple those two parts of what is going on, every step has to be negative delta G overall otherwise it will not happen that is what makes it spontaneous, PEP going to pyruvate if just isolating creating of atp that requires energy input but so much energy is released when PEP get to pyruvate that compensates negative delta, every step is negative delta G very thing has to be favorable and negative delta G, exergonic
so reverse can be favorable adn exergonic, if you had to precisely reverse, like hexokirnase all of that would be unfavorable positive delta G in the reverse direction so in order to make that step and the glconeogenesis step process it gets done in a different way,
OVERALL ALL NEGATIVE delta G
bc using atp up
Step 10 glycolysis
Step 10: PEP transfers a phosphate group to ADP to make ATP
This is substrate-level phosphorylation
The other product is pyruvate
In aerobic conditions (oxygen present), pyruvate is further oxidized in mitochondria
In anaerobic conditions (oxygen absent), pyruvate undergoes fermentation
Net yield of glycolysis
Net yield per glucose (6C): 2 pyruvate (3C) + 2 ATP + 2 NADH
Total ATP yield after oxidative phosphorylation: 6–8 ATP (see below)
FORMATION OF ACETYL COENZYME A
Occurs in mitochondrial matrix
Enzyme = pyruvate dehydrogenase complex
Pyruvate (3C) oxidized to acetate (2C)
Decarboxylation reaction produces CO2
Energy captured by formation of 2 NADH
Acetate is joined to coenzyme A, forming acetyl coenzyme A (acetyl CoA)
Net yield per glucose (2 pyruvate (3C)): yields 2 acetyl CoA (2C) + 2 NADH + 2 CO2
Total ATP yield after oxidative phosphorylation: 6 ATP
enzyme used in formation of acetyl coenzyme A
Enzyme = pyruvate dehydrogenase complex
citric acid cycle (also called Krebs or TCA)
Occurs in mitochondrial matrix
Acetate group (2C) of acetyl coA joins with oxaloacetate (4C), yielding citrate (6C)
Citrate recycled to oxaloacetate
Energy captured by formation of ATP, NADH and FADH2
ATP is formed by substrate level phosphorylation via GTP intermediate
Net yield per glucose: 2 acetyl coA (2C) yields 4 CO2 + 6 NADH + 2 FADH2 + 2 ATP
Total ATP yield after oxidative phosphorylation: 24 ATP
ELECTRON TRANSPORT CHAIN
Occurs at inner mitochondrial membrane (in bacteria, at the outer membrane)
Energy stored in reduced NADH and FADH2 is converted to ATP
Electrons from NADH/FADH2 enter stepwise electron transport chain to lower energies
Four complexes (I, II, III, IV) and coenzyme Q involved
Electrons from NADH → complex I
Electrons from FADH2 → complex II
Each NADH yields 3 ATP (but see below)
Each FADH2 yields 2 ATP
Complexes contain several classes of proteins and other molecules
Complexes reduce/oxidize each other by passing/receiving electrons
GLYCOLYSIS NADH YIELD ~2 ATP
- Glycolysis NADH are in the cytoplasm
- Shuttling electrons from these NADH into the mitochondria costs energy
- In skeletal muscle, brain, shuttle gives 2 ATP per glycolysis NADH
- In liver, kidney, heart, shuttle gives 3 ATP per glycolysis NADH
- Prokaryotes have no mitochondria and generate 3 ATP for each NADH
Net total is 36–38 ATP per glucose
ETC Complex 1
Complex I: NADH dehydrogenase
• Transfers two electrons from NADH to Coenzyme Q
ETC Complex 2
Complex II: Succinate-coenzyme Q reductase
- Transfers electrons to Coenzyme Q (in ETC)
- Dehydrogenates succinate to fumarate (in Krebs Cycle)
-Is the only enzyme complex that participates both in the Krebs cycle and ETC
-Is the only enzyme complex in the ETC not directly involved in proton pumping
ETC Complex 3
- Complex III: Coenzyme Q-cytochrome c reductase
- Picks up electrons from Q
Complex 4 ETC
Complex IV: Cytochrome c oxidase
- Picks up electrons from Complex III
- Inhibited by the poison cyanide
- Transfers electrons to oxygen → H2O
ETC End
- Protons pumped out by I, III, IV, forming gradient
- Proton gradient used by ATP synthase: H+ import linked to ATP generation
- Proton-motive force: energy released by flow of protons down gradient
- Chemiosmosis: flow of chemical species down gradient, generally through ion channel
- Coupling of ATP synthesis with proton flow
ETC image
As electrons passed alogn electron transport chain, they encounter coenzyme Q know structure of coenzyme Q like everything in ETC, everything ETC has a sort of special ability to cycle between an oxidized form and a reduced form, coenzyme Q oxidized form ubiquinone and oxidized form ubiquinol* so ubiquinone sitting in membrane, takes two electrons, becomes ubiquinol passes on those and goes back to beign ubiquinone.
Another v important structure is cytochrome structure- lots of cytochromes within electron transport chain all have porphorin ring structure** need to memorize 5 membered rings with nitrogen around a central iron, and one of the other fun facts about cytochromes pops up a bunch on MCATs, most constituents of eTc can take two e at a time, most time electrons passed down ETc in pairs, but when the ETC gets to cytochromes they have to go single file, cytochrome can only take one electron at a time* and that is because the cytochrome is relying on iron* to carry and transport its electrons and so iron only has 2 states Fe2+ or Fe3+, 2 possible oxidiation states*
Flavoproteins
Contain a prosthetic group that is a nucleic acid derivative of riboflavin:
Flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN)
Prosthetic group generally required for catalytic activity
Complex I of the ETC contains a flavoprotein (FMN)
Complex II of ETC contains a flavoprotein (FAD)
Flavoproteins are also important in DNA repair and free-radical scavenging
Ubiquinone
• Ubiquinone = Coenzyme Q10, = “Q”
Allows transfer of electrons as it alternates between oxidized and reduced forms
Oxidized form is ketone, ubiquinone
Reduced form is alcohol, ubiquinol
Complex II of ETC includes Q
Q is lipophilic, soluble and mobile in the mitochondrial inner membrane
Facilitates electron transfer
Ubiquinol can serve an antioxidant role in cells to protect them from oxidative damage
ubiquinone
Oxidized form is ketone
Reduced form is alcohol, ubiquinol
Complex II of ETC includes Q
ubiquinol
Reduced form is alcohol
Complex II of ETC contains Q
Cytochromes
Contain prosthetic heme groups
Heme groups consist of Fe2+ within an organic ring (called a porphyrin ring)
Cytochromes can take one electron at a time (alternating between Fe3+ and Fe2+)
Cytochromes are largely bound to inner mitochondrial membrane
Often combine to yield larger functional units
Example: cytochromeb and cytochromec1 yield Complex IIIc
Example: cytochromea and cytochromea3 yield Complex IV
regulation of aerobic respiration
In general, flux through metabolic pathway can be regulated by:
- Substrate availability
- Concentration of enzymes
- Allosteric regulation of enzymes
• Covalent modification of enzymes (e.g., phosphorylation)
OXYGEN DEPRIVATION
Oxygen deprivation stops last step of electron transport (reduction of H2O)
Entire chain is blocked, no ATP production
No oxygen results in anaerobic fermentation/glycolysis (2 ATP per glucose)
In humans, end product is lactate
In yeast, end product is alcohol + carbon dioxide (think bubbly champagne)
NAD+ is regenerated during anaerobic fermentation
INHIBITORS OF RESPIRATION
Cyanide binds to iron in cytochrome a3 (part of complex IV) and blocks entire chain
NADH can no longer be oxidized
Dinitrophenol carries H+ across membrane and destroys H+ gradient: proton uncoupler
NADH can still be oxidized and electrons flow down chain, but no ATP produced
image of NAD+ from metabolism
image of proton uncoupler
Dinitrol phenol proton uncoupler** makes holes in membrane that destroys proton gradient
-protons come back into matrix through membrane instead of going through atp synthase and making atp*
Question 11 (Blueprint qbank 11/21)
Which statement(s) regarding the regulation of glycolysis is/are true?
I. Each step of glycolysis can be directly up- or downregulated by the presence of certain coenzymes or products.
II. Glycolysis and gluconeogenesis share all of the same enzymes, since one process is the exact reverse of the other.
III. Glucose 6-phosphate allosterically inhibits Step 1 of glycolysis.
IV. AMP allosterically activates Step 3 of glycolysis, but allosterically inhibits the final step of the glycolytic pathway.
A.
I only
B.
III only
C.
III and IV only
D.
I, II, and IV only
A.
I only
The glycolytic pathway has three major points of regulation. In other words, only three of its steps are strictly regulated (I).
B.
III only
Glucose 6-phosphate is the product of Step 1. Thus, when it is present in excess, it will inhibit the forward reaction of this step through a classic negative feedback mechanism. Step 1 is one of the three main points of regulation in glycolysis (III). CORRECT
C.
III and IV only
AMP does allosterically activate Step 3 of glycolysis, but it does not inhibit the final step (IV).
D.
I, II, and IV only
The glycolytic pathway has three major points of regulation. In other words, only three of its steps are strictly regulated (I). Glycolysis and gluconeogenesis do share most of the same enzymes. However, glycolysis is marked by three irreversible steps for which gluconeogenesis must use its own unique enzymes to catalyze the reverse reaction (II). AMP does allosterically activate Step 3 of glycolysis, but it does not inhibit the final step (IV).
hexokinase vs glucokinase
hexokinase- in lots of cells, higher affinity, lower km
glucokinase- in liver, lower affinity for glucose HIGHER KM, blood from small intestine flows first through liver hepatic portal vein liver gets first crack at glucose, if a lot of glucose you want liver to take some and store as glycogen but do nto want liver to be greedy and soak up so much glucose that there isn’t enough available for other organs that come later by having an enzyme with low affinity for glucose, means liver will only hold onto glucose if excess so much glucose present, if not a lot of glucose liver will not soak it up and deprive other organs**
Glycolysis step 1 part 2
Glycose comes into cell and broken down for making ATP, happens in cytoplasm consists of ten steps
- For step 1. Glucose comes in, hexokinase phosphorylates it source of it is atp, after that reaction we have glucose 6 phosphate, most cells hexokinase iso form glucokinase operates in liver and pancreas, glucokinase has lower affinity in liver what you want! Don’t want liver to hog glucose because goes to liver first, traps it in the cell and then also as soon as have glucose 6 phosphate that molecule is no longer part of gradient, so no more glucose can come into cell passively keeps phosphorylating, keeps concentration low in cell’s cytoplasm to facilitate more passive entry of glucose in cell*
***keep concentration of glucose low in cell in cytoplasm by converting it immediately to G-6P similar but not ht same thing, doesn’t count as glucose so not part of gradient so goes down passively
g6p not part of gradient! so not seen as glucose, glucose concentration in cell’s cytoplasm still very low - Cell hasn’t yet committed to doing glycolysis, glucose comes in it is phosphorlated, glucose 6 phosphate can participate in other pathways besides glycolsis but following it through
Glycolysis step 2, 3
(cnt.)
Isomerase enzyme glucose6P to F6P
step 3 next phosphorylation spending another ATP here to make fructose 1,6,bisphosphate* this is the committed step of glycolsis*
the first step is also a very exothermic negative delta G step, this one is very exothermic, very negative delta G and cell will only do it if sure it wants to continue on through glycolysis*
so there are a few molecules that act as regualtors of phosphofructokinase= HIGH ATP inhibits phosphofructokinase purpose of whole pathway is to make ATP, if already have a lot of it shut it down, don’t go through effort to make more.
Other allosteric regulator of phosphofructokinase is citrate** which is formed early in Krebs cycle first step, and so if citrate v high binds to phosphofructokinase tells cell there is a backlog lower down in pathway and maybe cell should hit pause on glycolysis for a while*
Glycolsis steps 4,5,6
(cnt.)
4 and 5- Then enzyme aldolase splits fructose1,6,bisphosphate into DHAP and GAP (or G3P, used more on MCAT), after split it get molecule of DHAP and molecule of G3P but only GAP/G3P can proceed to part 2, little triose isomerase to turn DHAP into GAP so everything can move onto second half of lgyoclsysi
Next part 2- step 6= now 2 infront GAPs proceeding on, next step dehydrogenase enzyme, dehyrogenases want to remember as beign associated with oxidation reduction eactions, specificaly ones that invovle NAD+ or FAD**
As we proceeding here and making 1,3,bisphosphoglycerate from G3P reducing two equivalents of NAD+ to NADH*
- NADH energy storage molecule and we are if conditions are aerobic, oxygen present can trade in NADH through ATP later* through electron transport chain, more temporary energy storage form
1,3, bisphophoglycerate (step 6 and 7 of glycolysis part 2)
1,3, bisphophoglycerate- very very high energy molecule, higher energy than ATP that is why can directly transfer one phosphate group onto ADP to make ATP* phosphorylation occurs twice since 2 molecules 2 ATPs
This is an example of substrate level phosphorylation* means directly put phosphate group onto ADP to make ATP didn’t use atp synthase or the ETC, we are doing it in a more direct transfer of phosphate group*
Basically all atp made by enzyme atp synthase later made through oxidative phosphroaltion* any other time making atp its always subtrate level phosphorylation*
Step 8-10 glycolsis (cnt. )
step 8- 3 phosphoglycerate, mutase makes 2-phosphglcyerate, enolase enzyme takes out water makes specifically phosphenolpyruvate, which is another very vyer high energy moelcules
A higher special energy molecule, higher energy then atp, substrate level phosphorylation, so the phosphate group goes onto ADP get ATP and left with pyruvate
Mutase in glycolysis
Mutase= literally moves a phosphate group from one carbon to a different carbon, so can see what mutase accomplishes is that have 3 phosphoglycerate end up with 2 phosphoglycerate phosphoglyerate group moves over!
So either direction is possible depdening on specifc reaction
Kinase in glycolysis
= part of group of enzymes called transferases*
we normally think of kinases as taking phosphate group from atp and put onto something else* but pyruvate kinase is transferring a phosphate group but in the other direction, putting phosphate group onto ADP to make ATP*
phosphorlyation is a covalent modification*
For the preparation of Acetyl-CoA=
Preparation of acetyl- CoA is now in matrix produces acetyl CoA and releases Co2, in process per pyuruvate one NADH also gets generated, so if we were to do our bookeepign on per glucose basis making 2 NADHs at this step* because have 2 pyruvates***
- Pyruvate dehydroganse enzyme that does this- memorize names of other cofactors, TPP, lipoate and FAD are also necessary to have present in order for pyruvate dehydrogenase to do its job
- Structure- sulfur huge lone pair over its head how coenzyme A attaches to acetyl group and other things its binding to, do not need to memorize the whole structure of aceyl-CoA but be familiar with these parts, pantothenic acid, beta-mecaptoethylamine, modified adenosinediphosphate molecule*
Krebs cycle cnt.
is isocitrate, one C shorter than others lose it by CO2 lost; alpha ketoglutamate to succinyl-co-A down to 4 carbons generating another NADH (first NADH generated from isocitate dehydrogenase to alpha-ketoglutarate), succinyl-coA is the third example of another very high energy molecule to participate in substrate level phosphorylation* making ATP from ADP+Pi can also think how after alpha-ketoglutmate coenzymeA went on molecule to prime it then succinyl-coa goes to succinate, make ATP through substrate level phosphorylation but also released coenzyme A again* in this case labeled on image as CoA-SH
atp technically adp + PI forms GTP then that is converted to ATP
what step exactly does GTP come in? so can draw on diagram for a blink of an eye, substrate level technically produces GTP then convert to atp
- Now moelcule symmetrical can’t tell what is what, something has to be reduced which is FAD reduced to FADH2 succiante to fumarate*fumuarte lost hydrogen so more oxidized form, fewer bonds to H* biochem point of view easier to say lost H so that is oxidation, and gains H is reduction easier to see H*
Krebs cycle cnt 3.
What is the energy yield after Krebs?
Fumarase to malate added water across the double bond because malate has an OH* and then malate dehydrogenase oxidaize that Oh to a ketone* oxidation if put orgo hat on the malate is oxidized to oxaloacetate and NAD+ is reduced* to NADH*
ENERGY YiELD krebs cycle for every 1 glucose, there are 2 molecules of acetyl co-a because two moelcules of pyruvate, and if we think about for one molecule of acetyl-coa enters krebs cycle if add it all up get 3 NADHs, 1FADH2 and 1 ATP* = with x2, gets 6 NADH, 2 FADH2, and 2 ATP
Fermentation
Under anaerobic conditions cell can do glycolsis and then fermentation, cannot carry on through Krebs cycle or ETC which requires oxygen as final electron acceptor*; technically theoretically it could do krebs cycle, but the way the cell has chosen there has to be some way to regerenate NAD+ and for whatever reason the system has evolved pyruvate is converted to lactic acid or ethanol in the reaction that will regenerate NAD+ no theoretical reason why do not do krebs cycle, maybe not as adaptive because such an ordeal so many reactions why do all that
Fermantion in us and most bacteria, pyruvate reduced to lactic acid, at the same time, NADH is oxidized to NAD+
Normally when NADH drops off its electrons at the beginning of the electron transport chain, it goes back to its NAD+ form* that is super important in order to keep doing glycolsis you need to have NAD+ so if cell has converted all its NAD+ to NADH it can’t keep doing glycolsis and you want to keep doing glycolsis first fermentation reaction
Yeast is a different process converts pyruvate to acid aldehyde then ethanol can regenerate nad+
How many electrons can cytochrome C take at a time?**
Most constituents of ETC can take two e at a time/most time electrons passed down ETC in pairs
But when the ETC gets to cytochromes they have to go single file, cytochrome can only take one electron at a time* and that is _because the cytochrome is relying on iron*_ to carry and transport its electrons and so iron only has 2 states Fe2+ or Fe3+, 2 possible oxidiation states*
NADH mechanism
Yeast is a different process converts pyruvate to acid aldehyde then ethanol can regerneate nad+; mechanism on the bottom, H and its electrons acts as a nucleophile* attacks c of acetaldehyde and reduces it ends up with ethanol and NAD+
After we eat, goes to liver stores as glycogen, then first thing in morning body breaking down that glycogen to give us glucose*
