Last Chunk of Exam 1

Catbolic Pathway

Enzymes in Metabolic Pathways

________: Enzymes in a pathway can function to breakdown biomolecules and release energy.

• Eg. The steps involved in the breakdown of glucose to lactate.

Anabolic Pathway

Enzymes in Metabolic Pathways

________: Enzymes in a pathway can also make complex biomolecules, needed by the cell, from small precursors.

• Eg. The steps involved in the synthesis of amino acids from simplier precursor

regulatory enzymes

Metabolomics

Metabolic pathways

• Numerous interconnecting pathways, there needs to be signals to indicate - rate, quantity and timing of each enzyme, specifically these enzymes need to be functionally compartmentalized.

• Enzymes are tightly controlled by ____________.

signals

Metabolomics

Regulatory Enzymes

• catalytic activity increases or decreases in response to certain ______.

• allows the cell to meet changing needs for energy and biomolecules.

Unfavorable

Roles of Regulatory Enzymes

• Pathways may contain __________ reactions - An unfavorable reaction can be driven forward by a favorable reaction

  • E.g. If the equilibrium contsant for the 2nd reaction favors W or X, but 3rd reaction uses X with a more favorable equilibrium constant, this can drive the 2nd reaction forward.

Regulated

Roles of Regulatory Enzymes

• Pathways are ________- Substrates or products of one step in the pathway can interact with one of the enzymes to affect its activity and alter the effeciency of the entire pathway

  • E.g. Product Z may inhibit E1, to down-regulate the pathway.

decrease

Roles of Regulatory Enzymes

• Cells do not waste energy, or building blocks, making biomolecules that are already plentiful enough, or that are not needed under a given enviornmental condition.

  • In this case, a pathway may be down-regulated to _____ its production of end-product.

increase

Roles of Regulatory Enzymes

• If a cell needs more energy, or more of a particular biomolecule, under a given set of circumstances, the cell will produce more.

  • In this case, a pathway may be up-regulated to ______ its production of the end product.

regulatory enzyme

Characteristics of Regulatory Enzymes

• The first enzyme (E1) is often the ________. This more effecient since other steps do not waste energy unnecessarily.

Michaelis-Menten

Other enzymes follow _________ kinetics, but regulatroy enzumes usually do not.

• All regulatory enzymes do not follow Michaelis-Menten kinetics.

multi-subunit

Regulatroy enzymes tend to be ________ proteins.

Allosteric enzymes

Modulation of Regulatory Enzymes

• ___________- function through reversible, noncovalent binding of regulatory compounds called allosteric modulators or allosteric effectors (small metabolites or cofactors)

  • Reversible covalent modification

  • Binding of a separate regulatory protein/s

  • Removal of peptide segments ny proteolytic cleavage

modulator binding site

Allosteric Regulation of Enzymes

• In many allosteric enzymes, the substrate binding site and the __________ are of different subunits, the catalytic (C) and the regulatroy (R), respectively.

activity

Allosteric Regulation of Enzymes

• The binding of positive regulator and the absence of a negative regulator increases ________.

Homotropic

Allosteric Regulation of Enzymes

______- regulation in which the substrate and modulator are identifcal

Heterotropic

Allosteric Regulation of Enzymes

______- regulation in which the modulator is a moelcule other than a substrate

Aspartate transcarbamoylase

______________(ATCase) - catalyzes the formation of carbamoyl aspartate, an early step in pyrimidine biosynthesis.

• Regulatory Enzyme

Quaternary

The _____________ Structure of Aspartate Transcarbamoylase

Diverge

The Kinetic Properties of Allosteric Enzymes _____from Michealis-Menten Behavior

sigmoid saturation curve

Allosteric Enzymes

• Plot of V0 versus [S] usually produce a _________, rather than a hyperbolic curve.

• [S]0.5 or K0.5 represents the [S] giving half-maximal velocity of the reaction which is different from the Km

[S]

Allosteric Enzymes

• A relatively small increase in ____ in the steep part of the curve causes a comparatively large increase in V0*

• Activators

• Inhibitors

Modulations to alter either K0.5 or Vmax

• For heterotrophic allosteric enzymes

  • _______: may cause the curve to become more hyperbolic.

  • ________: may cause the curve to become more sigmoidal.

Homotrophic modulator

A substrate that causes a conformational change in an enzyme to enhance its own binding is a(n):

___________

reversible

Some enzymes are regulated by _______ covalent modification

Protein Kinases

Phosphoryl Groups Affect the Structure and Catalytic Activity of Enzymes

• __________ = catalyze the attachement of phosphoryl groups to specific amino acid residues (Ser, Thr, Tyr, His)

phosphoprotein phosphatases/protein phosphatases

Phosphoryl Groups Affect the Structure and Catalytic Activity of Enzymes

• ___________________= remove phosphoryl groups from the same target proteins

Phosphorylation

Regulation of Muscle Glycogen Phsophorylase (Regulatory Protein) Activity by _________

• Glycogen phsophorylase is regulated by 2 other proteins → phosphorylase (adds a phosphate) and phosphoprotein phosphatase 1 (removes a phosphate)

cleaved

Regulation by Proteolytic Cleavage of an Enzyme Precursor

• Protein/enzyme needs to be ____ for it to be activated

Zymogen

______- inactive precursor that is cleaved to for an active protease

Proprotein or proenzyme

________- precursors that are cleaved to form other proteins (Already activated)

Coagulation

A Cascade of Proteolytically Activated Zymogens Leads to Blood ______________

Regulatory Cascade

______ = a mechanism that allows a very senestive response to ‘and amplification of’ a molecular signal

• Example = formation of a blood clot

Blood Clot

________= aggregate of specialized cell fragments that lack nuclei (platelets) cross-linked and stabilized by proteinaceous fibers consisting maingly of the protein fibrin (dervied from the soluble zymogen fibrinogen)

thromboxanes

Blood Coagulation Cascade (1)

• Caused by collagen exposure to blood (tissue damage)

• Causes the release of signaling molecules such as _______to stimulate the activiation of additional platelets.

fibrin

Blood Coagulation Cascade (2)

• Fibrinogen is converted to _____ by the preoteolytic removal of amino acid residues.

• Thromin - serine protease that catalyzes peptide removal

• Factor xiia - transglutaminase enzyme that catalyzes the formation of covalent cross-links between fibrins

Intrinsic pathway

Blood Coagulation Cascade

_______- involes all compounds found in the blood plasma (internal injury)

Extrinsic pathway

Blood Coagulation Cascade

______- tissue factor pathway = involves the protein tissue factor (tf) which is not present in blood

transductions

Bioenergenetics is the stidy of energy ________ in living systems.

• How do cells extract energy from the enviornment and sue this energy to synthesize biomolecules?

thermodynamics

Biological energy transuctions obey the laws of ________

• First Law of Theormodynamics: Energy may change form, and may be transported, but energy cannot be created or destroyed.

• Second Law of Thermodynamics: The entropy (randomness) of the universe will always increase

Universe

Thermodynamic Laws apply to the ______(Biochemical)

• The reacting system and its surroundings.

form

Energy Transofrmations in Living Organisms

• The first law of thermodynamics: in any physcial or chemical change, the total amount of energy in the universe remains constant, although the _____ of energy may change.

catabolism

The Relationship Between Catbolic and Anabolic Pathways

• __________- the degradative phase of metabolism

  • releases energy

anabolism

The Relationship Between Catabolic and Anabolic Pathways

• _________(biosynthesis) - the building phase of metabolism

  • requires energy

Diverge

Catabolic Pathways and Anabolic Pathways _________

• Acetate (Acetyl-CoA) is at the center of a bunch of catabolic and anabolic pathways in living organisms

Gibbs free energy

Thermodynamics

• __________, G, a measure of the amount of work a system can perform at constant temperature and pressure.

DeltaG

____: Changes in G allows prediction of the direction of chemical reactions (i.e. whether favored and the equilibirum position)

• Exergonic reaction; releases free energy -Delta G (Favorable)

• Endergonic reaction; gains free energy +Delta G (Not favorable)

H

Enthalpy, ___, or heat contant, reflects the number and kinds of bonds in reactants (substrate, S), and product, P. Units: J/mol

• Exothermic reaction, heat is releases -Delta H

• Endothermic reaction heat is absorbed +Delta H

increase

Entropy, S, measures randomness or disorder. Units J/mol x K

• Entropy ____; gain entropy when products are less complex or more disordered than reactants +Delta S

  • The change in Gibbs free energy: (view equation)

Standard Free Energy Change → ______

• Free energy associated with a specific equation at a specific concentration/pressure/temperature

• Reacting systems tend to move toward equilibrium.

  • At equilibrium, the forward and reverse reaction rates are equal. Also, the concentrations of reactants and products define the equilibrium constant.

Tendency toward equilibrium represents a driving force that can be expressed by the _____ for the reaction.

constant

DeltaG’o is a measure of how far a reaction must go to reach equilbirum, when initial concentrations of each component are 1M, with standard state conditions (1atm and 298K)

• DeltaG’o is ________ for a given reaction

actual

Kinetics vs Thermodynamics

• The actual free energy for a reaction depends on the initial concentrations of substrates and products, and on the tempature.

• These are unlikely to be standard conditions.

  • In this equation, the concentration terms and temperature are the ____ conditions.

forward direction

When Delta G < 0 reaction tends to go in the __________

Reverse direction

When Delta G > 0 reaction tends to go in the _______

equilbirum

When Delta G = 0 the reaction is at _______

• But this does not say how fast, just where it will end

DO NOT

Gibbs Free Energy

• Reaction rate constant, k, is a function of DeltaG(TS) (Delta G (Tcat) < Delta G (Tuncat)

• Equilibrium constant K’eq is a function of DeltaGo

• Enzymes _________ affect the rate of equilibirum, only the reaction rate and the rate of approach to equilibrium.

coupled

Biochemical Bookkeeping

• Standard free energy changes for sequention reactions are additive

• Therefore, a thermodynamically unfavorable reaction (DeltaG’o > 0 or endergonic) can be _____ to a thermodynamically favored reaction (DeltaG’o < 0, exergonic) to drive the unfavorable reaction forward.

Currency

ATP is the Energy “_____” of cells

• ATP hydrolysis is a coupling reaction that couple reactions

exergonic

• The DeltaG’o for ATP hydrolysis is large and negative

• The _____ process of ATP hydrolysis is coupled to many endergonic reactions and processes.

group transfer

In metabolism, it is not ATP hydrolysis, but ________ that couples the energy of ATP breakdown to endergonic reactions

• i.e. Phosphoryl, pyrophosphoryl, or adenylyl group transfer.

• For some mechanoenzymes, energy of ATP hydrolysis drives conformational changes to drive reactions.

  • e.g. DNA helicase hydrolyze ATP to unwind DNA

3

Hydrolysis of ATP

• There are __ phosphates that can be hydrolyzed

nucelophilic

Group Transfer by ATP 1

• each of the three phosphates of ATP is susceptible to _________ attack

free energies

Group Transfer by ATP 2

• Recall in thermodynamics, what matters is the relative energies of the reactants and the products

• The pathway from reaction to products is not important.

• Therefore, you can add the _____ of the two reactions to get the overall free energy for the system of coupled reactions

Carbohydrates

What is the most abundant biomolecule on earth?

Oxidized

Carbohydrates

• _____ to produce energy in non-photosyntehtic organisms

• Structural

• Protective

Carbohydrates

• Polymers are both ____ and _________ in some organisms

hydroxyl groups

Carbohydrates

• Lubricates joints, involved in cell-cell adhesion and recognition

• Glycoprotein or glycolipid acts as signal for intra and intracellular transport

• Aldehydes or ketones with at least two ___________, or substances that yield such compounds on hydrolysis

Many carbohydrates have the empirical formula → ______

*Carbohydrates by themselves → not usually signaling molecule: intract with lipids/proteins

Carbohydrates s

Introduction to ________

Monosaccharides

Classification of Carbohydrates

• _________ = simple sugars, consist of a single polyhydroxy aldehyde or ketone unit, example D-glucose

  • Carbohydrates D isomers, Amino Acids L isomers

Oligosaccharides

_________ = short chains of monosaccharide units, or residues, joined by glycosidic bonds.

Disaccharides

_________ = oligosaccharides with two monosaccharide units

example: sucrose (D-glucose and D-fructose)

Polysaccharides

___________ = sugar polymers with 10+ monosaccharide units

examples: cellulose (linear), glycogen (branches)

• Aldose

• Ketose

Monossacharides

• _____ = aldehyde group is at an end of the carbon chain

• ______ = ketone group is at any other position other than the end.

  • Contains 2 or more hydorxyl groups - steroisomeric forms

D-Glyceraldehyde an aldotriose

Dihydroxyacetone a ketotriose

D-Glucose an aldohexose

D-fructose, a ketohexose

D-Ribose an aldopentose

2-Deoxy-D-ribose an aldopentose

chiral carbon atom

Stereochemistry of Monossacharides

• All monosaccharides (expect dihydroxyacetone) contan 1+ ____

  • Occur in optically isomeric forms (D,L enantiomers)

Enantiomers

_______= two different optical isomers that are non-superposable mirro images.

2^n

In general, a molecule with n chiral centers can have __ stereoisomers

carbon atoms

Sugar stereoisomers - _____ to which the hydroxyl groups are attached are chiral centers.

• Enzymes that act on sugars are stereospecific (most common sugars in nature → D_

Aldoses and Ketoses

________

The position of the carbonyl carbon

What chemical feature determines if a sugar is an aldose or ketose?

Epimers

_______: two sugars that differ only in the configuration around one carbon atom

cyclic (ringed) structures

Cyclization

• In aqueous solution, aldotetroses and all monosaccharides with 5+ backbone carbon atoms occur as ________

• Formed by a covalent bond between the carbonyl group and the oxygen of a hydroxyl group

ring/cyclic

Cyclization

• Hemiacetals or hemiketals

  • reaction between alcohols and aldehydes or ketones

  • product of the first alcohol molecule addition

  • a five or six membered ____ structure forms if the -OH and carbonyl groups are on the same molecule.

glycosidic bond

Cyclization

Acetal or ketal = product of the second alcohol molecule addition - forms a _______

Review

Formation of Hemiacetals or Hemiketals

hemiacetal linkage

Formation of the Two Cyclic Forms of D-Glucose

• Reaction between the aldehyde group at C-1 and the hydroxyl group at C-5 forms a ______

• Mutarotation = the interconversion of alpha and Beta anomers

Pyranoses

Pyranoses and Furanoses

• _______ = six membered ring compounds

  • form when the hydroxyl group at C-5 reacts with the aldehyde group at C-1

Furanoses

Pyranoses and Furanoses

• _______ = five-membered ring compounds

  • form when the hydroxyl group at C-5 reacts with ketone group at C-2

perpendicular

Hawroth Projection

• Haworth perspective formulas = more accurate representation of cyclic sugar structure than Fischer prohections

  • six-membered ring is titled to makes it plane almost ____ to that of the paper

  • bonds closets to the reader are drawn thicker than those farther away

Review

Symbols and Abbreviations for Monosaccharides and Derivatives

• Review

Review

Glycosidic Bonds - Acetals and Ketals Review

Aldehydes

The Reducing End

• ________ - formation of a glycosidic bond renders a sugar nonreducing

Anomeric

Reducing end - the end of a disaccharide or polysaccharide chain with a free_______ carbon

Lactose

Disaccharides

• _____ - is a reducing disaccharide - anomeric carbon is availiable for oxidation