Exam 2_Concepts Flashcards

Question

# Metabolism How is rxn selectivity accomplished in nature and in eukaryotes?

Answer 1

In Nature: Substrate specificity of particular enzymes In Eukaryotes: Compartmentalization of organelles

Answer 2

"add image; from ch 15 pg 443 of txtbook"

Answer 3

By controlling the... 1. Amount/Concentration of enzymes 2. Catalytic activity of enzymes 3. Accessibility of substrates

Answer 4

1. Pyranose (hemiacetal) form is favored over open (α-hydroxy aldehyde) form b/c of its hydroxyl groups are equatorial to the compound 2. Open form of aldoses react nonenzymatically w/ protein amino groups to give α-amino ketone derivative of proteins 3. Glucose, compared to other aldoses, has a low tendency to modify/damage proteins

Answer 5

Break down of glucose in conjunction with generating ATP. Produces: 2 pyruvate molecules and 2 ATP Anaerobic process

Answer 6

Production of glucose.

Answer 7

Process that generates ATP anaerobically and organic compounds act as both electron donors and acceptors.

Answer 8

Process that does NOT require O2.

Answer 9

Process that DOES require O2.

Answer 10

Organisms that can only live in anaerobic (no O2) environments b/c O2 is toxic to them.

Answer 11

Organisms that can live in both anaerobic (no O2) and aerobic (has O2) environments.

Answer 12

1. Phosphorylation (by ATP) 2. Retroaldol Cleavage 3. Keto-Enol Tautomerization 4. Oxidation of aldehyde to thioester 5. Acylation of phosphate (by thioester) 6. Phosphorylation (by phosphoglyderate) 7. Transphosphorylation 8. β-elimination (of phosphoric acid) 9. Phosphorylation (by phosphoenolpyruvate)

Answer 13

Stage 1-Trapping and Preparation Phase: -trap glucose in the cell and form a compound that can be readily cleaved into phosphorylated 3- carbon units Stage 2: Isomerization of 3-carbon compound -3-carbon phosphorylated sugar is isomerized into G3P -Sugar ring gets opened via cleavage of a C-C bond Stage 3: ATP Harvesting -3-carbon fragments are oxidized to pyruvate and 2 ATP are harvested from 1 molecule of glucose

Answer 14

Enzymes that catalyze the transfer of a phosphoryl group from ATP to an acceptor.

Answer 15

Role: TRAPS GLUCOSE IN THE CELL How: Catalyzes the phosphorylation of glucose into Glucose-6-Phosphate Why works: Binding of glucose to hexokinase induces a major conformational change (INDUCED FIT) that PREVENTS THE RXN OF WATER (instead of glucose) WITH ATP.

Answer 16

Mg2+ Why: Mg2+ helps to neutralize the negative charge of the phosphate groups on ATP which makes ATP more an electrophile thus making it more appealing to bond to for glucose.

Answer 17

A POSITIVELY CHARGED species that are ATTRACTED TO ELECTRONS They ACCEPT ELECTRON PAIRS in order to bond with a NUCLEOPHILE * usually positively charged BUT can also be neutral and have an atom w/out a full octet of electrons * get attacked by the most electron dense part of a nucleophile

Answer 18

Chemical species that DONATES A PAIR OF ELECTRONS to an electrophile in order to form a bond *ALL molecules with a FREE ELECTRON PAIR can act as a nucleophile.

Answer 19

Phosphoglucose Isomerase

Answer 20

Catalyze the 2nd phosphorylation step of glycolysis to trap the ketone - Fructose-6-Phosphate becomes Fructose 1,6-biphosphate * This step is a KEY CONTROL POINT for metabolism

Answer 21

Role: Catalyze the net retroaldol cleavage of Fructose 1,6-biphosphate into Glyceraldehyde 3-phosphate.

Answer 22

1. Substrate binding 2. Schiff base formation b/w the enzyme's active site Lys residue and the open-chain form of F-1,6-BP 3. Retroaldol cleavage to form an enamine intermediate of the enzyme and DHAP, with release of GAP (G3P) 4. Tautomerization and protonation to the iminium form of the Schiff base 5. Hydrolysis of the Schiff base w/ the release of DHAP

Answer 23

Role: Catalyze the isomerization which converts DHAP (dihydroxyacetone phosphate) into GAP (i.e. G3P, Glyceraldehyde 3-phosphate). *this rxn is reversible

Answer 24

Structure: αβ barrel= a 7-strand β barrel inside a 7-helix array When bound to a substrate: 1. Loop closes the active site 2. Forces intermediate enediol to undergo confirmation change causing it to get trapped in the active site of TIM 3. Confirmation change makes intermediate unfavorable for an elimination rxn that produces toxic compound, methyl glyoxal.

Answer 25

Control over the nature or rate of the products of a chemical rxn through control of the orientation of electron orbitals.

Answer 26

IT'S ALL ABOUT THE O-H AND C-OPO3 BONDS: When DHAP is in a confirmation where O-H and/or C-OPO3 bonds are PERPENDICULAR to the plane of the π-bond --> elimination is DISFAVORED -->leads to formation of methyl glyoxal (i.e. TOXIC) When DHAP is in a confirmation where O-H and C-OPO3 bonds are COPLANAR with 1 of the p-orbitals of the π-bond--> elimination is FAVORED--> allows for simultaneous generation of new π-bonds and cleavage of σ-bonds.

Answer 27

Since G3P can be used in glycolysis to form ATP, as DHAP is converted into G3P, G3P is removed and used in subsequent rxns in glycolysis. This creates a constant conversion of DHAP into G3P (i.e. Le Chatlier's Principle).

Answer 28

Used to pull the proton away from a carbon atom adjacent to a carbonyl group Glu residue=acts as a general acid-base catalyst-->takes a proton (H+) from carbon 1 and gives it to carbon 2 His residue=proton donor which helps to stabilize neg charge that develops on the C-2 carbonyl group

Answer 29

Phosphate group because if the enediol intermediate lost its phosphate group, it would become methyl glyoxal (i.e. TOXIC compound)

Answer 30

It has achieved CATALYTIC PERFECTION b/c it's close to the DIFFUSION CONTROLLED RATE.

Answer 31

Describes enzymes whose rates of catalyzation occurs as quickly as the substrate diffuses to the enzyme (i.e. diffusion limited)--> basically every time substrate and enzyme meet, rxn is catalyzed.

Answer 32

Rate of rxn is limited by the rate of encounter of the substrate with the enzyme.

Answer 33

Used: - 2 ATP - 1 molecule Glucose Created: -2 molecules of G3P/GAP (Glyceraldehyde 3-phosphate)

Answer 34

To catalyze the conversion of G3P/GAP into 1, 3-BPG (1,3-bisphosphoglycerate) * this is the 1st step of stage 3 * rxn involves coupling the oxidation and phosphorylation processes to avoid a high energy activation step Oxidation rxn= oxidation of the aldehyde to a carboxylic acid by NAD+ Phosphorylation rxn= carboxylic acid and orthophosphate are joined together to form the acyl-phosphate product.

Answer 35

1. Aldehyde substrate reacts with the sulfhydryl group of cystein to form a hemithioacetal 2. A hydride ion (H-) is transferred to a molecule of NAD+ that's tightly bound to the enzyme and adjacent to the cystein residue -creates a favorable compound for deprotonation of hemithioacetal by histidine 3. Deprotonation produces the products: NADH and a thioester intermediate *note: thioester intermediate's free energy is close to that of the reactants 4. NADH leaves the enzyme and gets replaced by a 2nd NAD+ -IMPORTANT step b/c (+) charge of NAD+ polarizes the thioester intermediate to facilitate the attack by orthophosphate 5. Orthophosphate attacks the thioester to form 1,3-BPG and the cysteine residue is freed

Answer 36

Because 1,3-BPG has a greater phosphoryl-transfer potential than ATP.

Answer 37

PHOSPHOGLYCERATE KINASE - it catalyzes the TRANSFER of the phosphoryl group from the acyl phosphate of 1,3-BPG to ADP. - 1,3-BPG becomes 3PG (3-PHOSPHOGLYCERATE) Type of Phosphorylation: Substrate-Level Phosphorylation

Answer 38

Mutase is an enzyme that catalyzes the intramolecular shift (i.e. within same molecule) of a chemical group.

Answer 39

Role: Move phosphate group from oxygen 3 to oxygen 2 (i.e. CONVERTS 3-Phosphoglycerate into 2-Phosphoglycerate) How: 1. 2,3-BPG is needed to activate Phosphoglycerate Mutase by phorylation of a histidine residue.

Answer 40

From isomerization of 1,3-BPG (an intermediate in glycolysis) which is catalyzed by 1. bisphosphoglycerate mutase and then 2. 2,3-biphosphoglycerate phosphatase (a Pi is removed here) This is done by ERYTHROCYTES (red blood cells).

Answer 41

1. Activate phosphoglycerate mutase (PGM) | 2. Regulate oxygen binding affinity of hemoglobin.

Answer 42

Catalyzes the dehydration of 2PG which adds a C-C double bond to form PEP (phosphenolpyruvate).

Answer 43

HIGH Why: Due to enol-keto tautomerization. -phosphoryl group traps molecule in its UNSTABLE enol form -when phosphoryl group is transferred to ADP, the enol (PEP) converts into a more stable ketone (Pyruvate)

Answer 44

Molecule switches back and forth between enol and keto form. By moving a H atom from an adjacent carbon atom to a carbonyl group of a keto compound= becomes enol form By moving a H atom from a carbonyl group to an adjacent carbon atom of a enol compound= becomes keto form.

Answer 45

Enzyme responsible: PYRUVATE KINASE (PK) Generates: 2 ATP

Answer 46

Necessary to keep glycolysis going. Methods: 1. Ethanolic fermentation - turns pyruvate into ethanol 2. Homolactic fermentation - turns pyruvate into lactate 3. Formation of acetyl CoA via oxidative decarboxylation of pyruvate

Answer 47

Role: Acts as a coenzyme to pyruvate decarboxylase which decarboxylates pyruvate. How: inverts the normal electron deficient polar reactivity of the ketone carbonyl thus allowing a carbanion to be formed on the carbon on pyruvate

Answer 48

1. Allosteric Control: enzymes respond to small molecules -milliseconds 2. Phosphorylation: controlled by kinases -seconds 3. Transcriptional Control: control enzyme conc. by controlling rate of protein production -hours

Answer 49

1. PKF (Phosphofuctokinase) 2. HX (Hexokinase) 3. PK (Pyruvate Kinase) Why: they catalyze "essentially" irreversible rxns

Answer 50

*PKF structure has 4 allosteric sites: 2 are catalytic sites and 2 are regulatory sites. Catalytic and regulatory sites do not share the same structural shape. 1. High [ATP] or High [citrate] inhibits PKF (*but AMP is the positive regulator of PKF) How: ATP binds to a specific regulatory site distinct from catalytic site which lowers PKF's affinity for F6-P-->slows down glycolysis. 2. Low [ATP] or Low [citrate] stimulates PKF activity 3. Decrease in pH increases the inhibitory effect of ATP which results in inhibition of PKF 4. PFK activity increases when ATP/AMP ratio is lowered Why: AMP reverses the inhibitory effect of ATP 5. F-2, 6-BP activates PFK by increasing PFK's affinity for F6P (substrate for PFK) and decreasing inhibitory effect of ATP

Answer 51

-Allosterically inhibited by high [G6-P] in muscle/brain (neg feedback) -This causes glucose to be converted into G6-P in the liver by GLUCOKINASE -The G6-P form in liver is used to store glucose as glycogen - If Hexokinase is active it converts glucose into G6-P form used for glycolysis and synthesis of glycogen, ribose or NADPH--found in muscle or brain - PGI catalyzes rxn of G6-P to F6-P - F6-P can become F1,6P (via PFK catalysis) or F2,6BP (via FBPase2) - F2,6BP acts as positive feedback for PFK activity and the conversion of ATP to ADP coupled with F6-P to F1,6BP - F1,6BP converts into ATP or Citrate and acts as neg feedback for PFK activity

Answer 52

Enzymes that are almost identical to one another | ex. hexokinase and glucokinase

Answer 53

PFK catalyzed rxn of F6-P to F1,6-BP *this is the first use of ATP: ATP is converted into ADP

Answer 54

Through use of PYRUVATE KINASE ISOFORMS -these prevent glycolysis from occurring simultaneously in dif parts of the body which would cause them to compete for energy resources Isoforms of pyruvate kinase: L (liver) Isoform: deactivated by phosphorylation when blood [glucose] low M (muscle, brain) Isoform: cannot be turned off by phosphorylation

Answer 55

Family of glucose transporter isoforms - Regulate it through mediated passive diffusion - Transporters found on cell membrane will transport glucose along conc. gradient - Transporters found within the cell on membranous vesicles are inactive - Transporters are activated by INSULIN

Answer 56

Formation of glucose from pyruvate