EK B1 Ch3 Metabolism I

Question 1

phosphate groups on ATP

Answer 1

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

Question 2

phosphoanhyride bonds

Answer 2

• hydrolysis is exothermic and spontaneous, can provide energy required for less energetically favorable reactions

Question 3

delta H

Answer 3

change in enthalpy -negative for exothermic reactions

enthalpy is the heat that is gained or lost in a reaction

Question 4

spontaneous reactions

Answer 4

delta G, change in Gibbs free energy is negative NOTE atp –> adp + Pi (gamma phosphate) has delta G <<<0 SO SPONANTEOUS AND NEGATIVE

Question 5

oxidative phosphorlyation

Answer 5

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+

Question 6

substrate level phosphorylation

Answer 6

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

Question 7

phosphorlyation

Answer 7

ATP is synthesized by teh addition of a phosphate group to adenosine diphosphate

Question 8

acteyl-coa

Answer 8

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

Question 9

Each citric acid cycle….

Answer 9

-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

Question 10

beta- oxidation

Answer 10

produces 1 nadh per two carbon versus 3 NADH in TCA/KREBS/ ctric acid cycle

Question 11

GTP in citric acid cycle

Answer 11

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!

Question 12

NAD+ in TCA

Answer 12

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

Question 13

NADH regulation in TCA

Answer 13

-citric acid cycle produces NADH! so if an excess of NADH builds up, the reactions slow down!

Question 14

metabolism fats and proteins into TCA

Answer 14

-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

Question 15

glutamic acid

Answer 15

5 c backbone can be converted into citric acid cycle intermediate alpha-ketoglutarate

Question 16

to be used for energy.. amino acids

Answer 16

• 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!

Question 17

ETC (NADH)

Answer 17

NADH loses electrons, is oxidized to become NAD+ - oxygen gains electrons, is reduced to form water!

Question 18

atp synthase

Answer 18

ex of oxidative phosphorylation

Question 19

type 1 diabetes

Answer 19

• autoimmune disease where the immune system attacks the beta cells of the pancreas

Question 20

glucogenoesis

Blueprint exam 4 details

Answer 20

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.

Question 21

Gluconeogenesis

Blueprint Exam 4 concept cont.

Answer 21

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.

Question 22

breaking down fats….

Answer 22

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

Question 23

Q13 Blue print

Which specific class of enzymes is primarily responsible for the release of free glycerol from stored triglycerides?

Answer 23

• 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).

Question 24

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

Answer 24

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.

Question 25

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.

Answer 25

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

Question 26

catabolic rxns

Answer 26

• Metabolism consists of two classes of chemical reactions: catabolic and anabolic
• Catabolic reactions break down larger molecules and release energy (exergonic)

Question 27

anabolic rxns

Answer 27

Anabolic reactions build up from smaller molecules and require energy (endergonic)

Question 28

Metabolic rxns are catabolic and anabolic…..

Answer 28

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

Question 29

ATP hydrolysis yields ………

Answer 29

ATP hydrolysis yields ADP + Pi , –7.6 kcal/mol energy

Question 30

Metabolic- redox reactions….

Answer 30

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

Question 31

Reduction in Metabolism

Answer 31

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)

Question 32

Oxidation in Metabolism

Answer 32

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

Question 33

Free energy

Answer 33

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

Question 34

ΔG =

Answer 34

ΔG = actual free energy change

Question 35

ΔG°’=

Answer 35

ΔG°’= free energy change under standard cellular conditions

Question 36

∆Go =

Answer 36

∆Go = free energy change under “standard conditions”

Question 37

standard cell conditions

Answer 37

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

Question 38

Aerobic respirations

Answer 38

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

Question 39

Substrate-level phosphorylation:

Answer 39

= phosphate transferred directly from substrate to ADP

Question 40

Oxidative phosphorylation

Answer 40

ATP made from energy stored in NADH, FADH2

Question 41

glycolysis

Answer 41

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

Question 42

Step 1 Glycolysis

Answer 42

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!

Question 43

step 2 glycolysis

Answer 43

Step 2: glucose-6-phosphate is isomerized to fructose-6-phosphate

Enzyme is an isomerase

Question 44

Step 3 glycolysis

Answer 44

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

Question 45

Step 4 of glycolysis

Answer 45

Step 4: fructose 1,6-bisphosphate is cleaved

Enzyme is aldolase (reverse aldol reaction)

Products = dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P)

Question 46

Steph 5 glycolysis

Answer 46

Step 5: DHAP is converted to G3P. Only G3P continues on through glycolysis

Second half of glycolysis = energy pay-off

Now step 6

Question 47

Step 6 glycolysis

Answer 47

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

Question 48

step 7 glycolysis

Answer 48

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

Question 49

step 8 of glycolysis

Answer 49

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

Question 50

Step 9 of glycolysis

Answer 50

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

Question 51

Step 10 glycolysis

Answer 51

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

Question 52

Net yield of glycolysis

Answer 52

Net yield per glucose (6C): 2 pyruvate (3C) + 2 ATP + 2 NADH

Total ATP yield after oxidative phosphorylation: 6–8 ATP (see below)

Question 53

FORMATION OF ACETYL COENZYME A

Answer 53

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

Question 54

enzyme used in formation of acetyl coenzyme A

Answer 54

Enzyme = pyruvate dehydrogenase complex

Question 55

citric acid cycle (also called Krebs or TCA)

Answer 55

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

Question 56

ELECTRON TRANSPORT CHAIN

Answer 56

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

Question 57

GLYCOLYSIS NADH YIELD ~2 ATP

Answer 57

• 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

Question 58

ETC Complex 1

Answer 58

Complex I: NADH dehydrogenase
• Transfers two electrons from NADH to Coenzyme Q

Question 59

ETC Complex 2

Answer 59

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

Question 60

ETC Complex 3

Answer 60

• Complex III: Coenzyme Q-cytochrome c reductase
• Picks up electrons from Q

Question 61

Complex 4 ETC

Answer 61

Complex IV: Cytochrome c oxidase

• Picks up electrons from Complex III
• Inhibited by the poison cyanide
• Transfers electrons to oxygen → H2O

Question 62

ETC End

Answer 62

• 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

Question 63

ETC image

Answer 63

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*

Question 64

Flavoproteins

Answer 64

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

Question 65

Ubiquinone

Answer 65

• 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

Question 66

ubiquinone

Answer 66

Oxidized form is ketone

Reduced form is alcohol, ubiquinol

Complex II of ETC includes Q

Question 67

ubiquinol

Answer 67

Reduced form is alcohol

Complex II of ETC contains Q

Question 68

Cytochromes

Answer 68

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

Question 69

regulation of aerobic respiration

Answer 69

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)

Question 70

OXYGEN DEPRIVATION

Answer 70

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

Question 71

INHIBITORS OF RESPIRATION

Answer 71

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

Question 72

image of NAD+ from metabolism

Answer 72

Question 73

image of proton uncoupler

Answer 73

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 74

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

Answer 74

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).

Question 75

hexokinase vs glucokinase

Answer 75

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**

Question 76

Glycolysis step 1 part 2

Answer 76

Glycose comes into cell and broken down for making ATP, happens in cytoplasm consists of ten steps

1. 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
2. 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

Question 77

Glycolysis step 2, 3

(cnt.)

Answer 77

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*

Question 78

Glycolsis steps 4,5,6

(cnt.)

Answer 78

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*

1. 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

Question 79

1,3, bisphophoglycerate (step 6 and 7 of glycolysis part 2)

Answer 79

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*

Question 80

Step 8-10 glycolsis (cnt. )

Answer 80

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

Question 81

Mutase in glycolysis

Answer 81

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

Question 82

Kinase in glycolysis

Answer 82

= 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*

Question 83

For the preparation of Acetyl-CoA=

Answer 83

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***

1. 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
2. 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*

Question 84

Krebs cycle cnt.

Answer 84

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

1. 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*

Question 85

Krebs cycle cnt 3.

What is the energy yield after Krebs?

Answer 85

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

Question 86

Fermentation

Answer 86

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+

Question 87

How many electrons can cytochrome C take at a time?**

Answer 87

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*

Question 88

NADH mechanism

Answer 88

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*