Welcome to BCMB / BIOL / CHEM 3100 Introductory...

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Welcome to BCMB / BIOL / CHEM 3100

Introductory Biochemistry

Please pick up handouts(duplicate sets at both ends of the front desk).

www.biology.arizona.edu

www.sussex.ac.uk

INSTRUCTORS FOR THIS COURSE

1st half of course:Professor Debra MohnenDepartment of Biochemistry and Molecular BiologyComplex Carbohydrate Research Center, Room 2044315 Riverbend Rd.Phone: 706-542-4458

email: [email protected]

2nd half of course:Professor Emeritus Daniel DerVartanianDepartment of Biochemistry and Molecular BiologyB316B Life SciencesPhone: 706-542-4620email: [email protected]

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INTRODUCTORY BIOCHEMISTRY

BCMB/BIOL/CHEM 3100

Fall Semester 2017

**10:10-11:00 AM, Mon. Wed. & Fri,

Room C127 - Life Sciences

** Breakout Session: 5:00-5:50 PM,

Tues. Room C127 – Life Sciences

COURSE TEXT:

Biochemistry: A Short Course, Third Edition. John L Tymoczko, Jeremy M. Berg, and Lubert Stryer. W.H. Freeman and Company, New York, 2015

SEE SYLLABUS for important information about the course

•Partial Class Notes will be available on the class website at least one day prior to lecture

•Class website (see syllabus for website)http://www.ccrc.uga.edu/~dmohnen/bcmb3100/list.html

•Grading: 100% from 4 exams(you have the opportunity to add up to 2 points to yourgrade if you turn in all requested homework, quizzes, groupand other assignments)

•You are strongly encouraged to form study groups

•Any handouts/exams not picked in the breakout session, will be available in the BCMB office (B Tower Life Sciences)

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•Read the chapter BEFORE CLASSSkim chapter (look at figures!)Bring partial notes to class and write on themRead in detailReread and integrate information from the notes andfrom the text. Pay attention to major concepts.

•Keep up!

•Work at the material every day

•Form study groups and meet regularly

•Complete homework by the due date and bring it to the breakout session.

•Bring calculator to all exams and breakout sessions. You may NOT use pencils, blue or red ink for the exam. YOU MUST USE BLACK PEN FOR THE EXAMS!!

Tips for doing well in BCMB/BIOL/CHEM3100

BCMB / BIOL / CHEM 3100Introductory Biochemistry

www.biology.arizona.edu

www.sussex.ac.uk

http://www.bbisolutions.com/content/uploads/2015/01/Red-Ebola-virus-high-res-2.jpg

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BIOCHEMISTRY

"... the central goal of the science of biochemistry is to determine how

the collections of inanimate molecules found in living organisms

interact with each other to constitute, maintain, and perpetuate

the living state."from Biochemistry, Albert L. Lehninger, 1975

Biochemistry is the study of the molecular basis of life. It is an empirical, reductionist, and rapidly

evolving discipline.

BCMB 3100 - Chapter 1

• History of BIOCHEMISTRY

• Important functional groups

• Four types of macromolecules in living organisms

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HISTORY OF BIOCHEMISTRY

1800’s: predominate theory to explain life was vitalism

vitalism: animate world obeys different chemical laws than inanimate world

1770-1774- Priestly showed plants produce oxygen, O2

consumed by animals

1773 - Rouelle - isolated urea from urine

1828 - Friedrich Wöhler - showed organic molecule (urea) could be synthesized from the inorganic molecule (ammonium cyanate). MOLECULES OF LIFE COULD BE SYNTHESIZED OUTSIDE A LIVING ORGANISM!

1862 - Louis Pasteur – disproved spontaneous generation*Showed sterilized solutions did not spontaneously form life. *Air required to introduce microbes. *Living organisms arise from living organisms++Still vitalist: “ferments” in yeast viewed inseparable from life

1897 - Eduard & Hans Buchner – DEATH OF VITALISM*Fermented sucrose into alcohol using yeast extract.*Chemical reactions occur outside living cells! *DEATH OF VITALISM. Enzymes = cell-derived catalysts. *Metabolism = chemistry.

Emil Fischer 1890 - lock-&-key model forsubstrate enzyme interaction.

1891 - configuration of D-glucose

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Early 1900s - 1st biochemistry departments established. Isolation of biomolecules, study of structure, function & role in metabolism

1926 - James B. Sumner - crystalized 1st enzyme (urease)& showed was protein

1930s - Linus Pauling & Robert Corey - x-ray crystallography of amino acids and peptides.

1950s - 3D structure of 1st proteins by x-ray crystallography Max Perutz hemoglobin

John Kendrew myoglobin

1953 - James Watson & Francis Crick - 3D structure of DNA. Molecular biology as part of biochemistry.

Current biochemical generalizationregarding living things

1. Life requires life

2. Biochemical reactions require catalysts

3. The information of life is transmitted in the genome

4. The Central Dogma of life information flow:

DNA RNAProtein

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BCMB 3100 – Chapters 1 & 2




Table 3.1

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General formulas - Organic compounds

Table 2.1

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General Formulas - Functional groups

General Formulas - Linkages

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There are four types of molecules in living cells:proteins, carbohydrates, lipids

& nucleic acids

The basic macromolecular compartments of living things are cells

Prokaryotic cells contain no nucleus or intracellular membranes and are usually unicellular (bacteria and archaea)

Eukaryotic cells contains membrane-bound organelles: nucleus, ER, Golgi, mitochondria, lysosomes, peroxisomes, chloroplasts (animals, plants, fungi, protists)

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Biochemists concentrate on certain “model” organisms for their studies.

Prokaryote: E. coli

Eukaryote: humans, mice, rats, yeast, arabidopsis, drosophila

Eukaryotic cell (plant)

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Eukaryotic cell (animal)

Viruses

• Adenovirus: Viruses consist of a nucleic acid molecule surrounded by a protein coat, ds DNA linear genome

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Be sure to see text (Chapter 1 & 2 ) for:

*SI for size units & terminology

o

Note: one angstrom (A) = 0.1 nm !!!

*subcellular organization

*types of organic compounds, linkages and functional groups (Table 2.1, pg 25)

in vivo versus in vitro

Notices:

First Breakout Session, Tuesday, August 15, C127, 5:00-5:50 pm

Chapter 2 and other homework will be given out & described in the Breakout Session on Tuesday.

Reading for this week and next: Chapters 1-3, 5.

During the breakout session you will be asked to turn in to me a GROUP SHEET with your group names and emails. You will

also, on that sheet, include a first in class short group report regarding research on our class mascot.

Handouts not picked up in class are placedin the BMB office.

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http://www.reed.edu/biology/professors/srenn/pages/teaching/web_2010/qaic_site/phylogeny.html

Meet our Class Mascot

the Naked Mole Rat (Heterocephalus glaber)

http://www.reed.edu/biology/professors/srenn/pages/teaching/web_2010/qaic_site/adaptation.html

Naked Mole Rat (Heterocephalus glaber)

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www. newswise.com

Naked Mole Rat (Heterocephalus glaber)

http://www.the-scientist.com/?articles.view/articleNo/32136/ title/Underground-Supermodels/

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PICK UP THE TWO HANDOUTS ON THE FRONT DESK

Opportunity for extra credit “homework” points

There are 2 errors in the class text book on page 27.

In the Breakout Session on Tuesday (tomorrow) turn in (individually) a sheet of paper with the following to get extra credit points:

(1) Your name(2) Briefly state the mistakes(3) Give the corrections

BCMB 3100 – Chapter 2

• Properties of the solvent of life: water

• Four types of noncovalent interactions

• Review of acid-base concepts, pKa

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WATER

• 60%-90% of most cells and tissues is water

• water is the solvent of life

• it is ESSENTIAL to understand the chemical properties of water in order to understand how molecules react in water

Space-filling structure of water

Covalent bond angle of

water

*water is a polar molecule with asymmetric charge

distribution

*geometry is tetrahedral due to shape of outer e- orbital of

oxygen

pg. 19

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Fig. 2.1, pg 19 Polarity of Small Molecules

• Water and ammonia each have a permanent dipole while CO2 does not

Water molecules have a high affinity for each other

• Water is cohesive

• water forms hydrogen bonds (~20 kJ/mol; 3-6 kcal/mol)

• attraction between slightly negative O and slightly positive H

• H bonds are directional (more stable when linear)

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Hydrogen bonding between

two water molecules

Hydrogen bonding by a water molecule

• A water molecule can form up to four hydrogen bonds

• Hydrogen bonds shown in green

• Water is partly ordered, H-bondscontinually form & break, average 3.4 H-bondsin liquid water

Fig. 2.1

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https://www.nyu.edu/pages/mathmol/textbook/wat_10A.gif

Liquid water~3.4 H-bonds / water

Solid water~4 H-bonds/water

Frozen water forms a crystalline lattice that is less

dense than liquid water

Water is an excellent solvent for polar molecules and molecules that ionize

* It weakens electrostatic forces & H-bonds by competing for their attraction

* it forms oriented solvation shells around ions

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Fig. 2.3

* life depends on the ability of water to dissolve polar molecules. A high [ ] of these molecules can coexist with water

*Molecules that dissolve readily in water are called hydrophilic. They can be polar or charged.

Structure of glucoseGlucose is an example of a very soluble molecule since it has five hydroxyl groups and a ring oxygen which can hydrogen bond with water Different short-chain alcohols have different

solubility in water

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*Some polar interactions, however, are essential for life. Biological systems have created water free microenvironments where polar interactions have maximal strength

*Molecules that are nonpolar (e.g. hydrocarbons) do not dissolved in water. They are called hydrophobic.

*Nonpolar molecules or groups tend to cluster together in water = hydrophobic “attractions”; hydrophobic effect

C6H14

C6H14

water

hexaneC6H14

C6H14

Two clustered hexane

molecules

Fig. 2.9

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Nonpolar solute molecules are driven together in water NOT because they have a high affinity for each other

Thus, there is a net gain in entropy when the nonpolar groups aggregate and water is freed from an ordered state.

BUT BECAUSE WATER BONDS STRONGLY TO ITSELF.

Water that surrounds nonpolar molecules is more restricted in its interaction with other water molecules.

Second Law of Thermodynamics: “The total entropy of a system and its surrounding always increases in a spontaneous process.”

• A synthetic detergent

• A 12-carbon tail

• Polar sulfate group

Sodium dodecyl sulfate (SDS)

Amphipathic: molecules that are both hydrophilic and hydrophobic

Are all molecules hydrophilic or hydrophobic?

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Challenge of the Week Aug 15, 2016

We are in the early stages of a “Freshwater Crisis” (Scientific American, August 2008)

Today one out of six people (> 1 billion) have inadequate access to water.

By 2050, as much as ¾ of the earth’s population could face scarcities of water.

What is minimum amount of water each person requires per year for drinking, hygiene and growing food?

What is minimum amount of drinking water each person requires per year?

PLEASE HAVE ANSWER TO TURN IN FOR BREAKOUT NEXT TUESDAY.





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There are four types of noncovalent bonds(reversible molecular interactions)

• Charge-Charge (Electrostatic)

• Hydrogen bonds

• Van der Waals bonds

• Hydrophobic interactions (hydrophobic effects)

Charge-charge interactions - attraction based on charge

* Charge-charge interaction: also called ionicbond, salt linkage, salt bridge, ion pair,(electrostatic attraction)

*In an optimal charge-charge interaction, distance between oppositely charged groups is2.8Å (compare to 1.54 Å in C-C bond)

Electrostatic bond: potentially strongest noncovalent interaction: ~40-200 kJ/mol(3-7 kcal/mole)

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Hydrogen bonds: a hydrogen atom is shared by two other atoms; can form between uncharged or charged molecules

*Hydrogen donor: atom to which H is more tightly associated. O-H, N-H

*Hydrogen acceptor: atom to which H is less tightly associated. O or N. The acceptor has partial negative charge that attracts H atom.

* Distance between 2 electronegative atoms involved in hydrogen bond = ~2.6-3.1Å

*Hydrogen bond energy ranges from ~2-20 kJ/mol(3-7 kcal/mol)

*Hydrogen bonds are highly directional

Hydrogen bonding between hydrogen acceptor and hydrogen donor

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Some biologically important H-bonds

Fig. 2.4

Van der Waals bonds: non-specific attractive force important when any two atoms are 3-4 Å apart. Most important when numerous atoms in one molecule come close to may atoms in another.

* weaker & less specific than electrostatic & H-bonds

* the distribution of electric charge around an atom changes with time

*Thus, at any instant charge distribution is asymmetric.This asymmetry around one atom encourages similarasymmetry in electric distribution around neighboringatoms, leads to attraction

*Attraction is distance dependent: most strong at Van der Waals contact distance

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• Strongly repulsive at short internuclear distances, very weak at long internuclear distances

• Van der Waals attraction is maximal when two atoms are separated by their van der Waals radii

• Van der Waals contact radius: 1.2-2.0Å

• Van der Waals contact distance : 2.4-4.0 Å

• Van der Waals bond energy: 0.4-4 kJ/mol (~1 kcal/mol). Only slightly larger than the average thermal energy of moleculesat RT (0.6 kcal/mol)

Effect of internuclear separation onvan der Waals forces

Van der Waals contact distance

Van der Waals contact radius

Fig. 2.6

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Hydrophobic interactions

* weak interations: 3-10 kJ/mol (~1 kcal/mol)

*Interactions between nonpolar molecules due totendency of water to bond strongly to itself

*Hydrophobic interactions are major driving forcefor folding of macromolecules, binding of substrates to enzymes, & formation of membranes

Noncovalent interactions in biomolecules

• Charge-charge interactions

• Hydrogen bonds

• Van der Waals interactions

• Hydrophobic interactions

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Water is a weak NUCLEOPHILE

*Nucleophile: electron-rich group due to negative charge orunshared paris of electron

*Nucleophiles tend to donate electrons to positively charged or electron deficient groups known as electrophiles

*Most common biological nucleophiles contain O, N, S or C

*High cellular concentration of water makes hydrolysis(cleavage of a bond such as anhydrides or peptide bonds bywater) a potential problem

*Nonbeneficial hydrolysis in organisms is prevented by:-biopolymer stability at physiological pH-inactive or inaccessible storage of hydrolases-two-step biosynthetic reactions using non-water nucleophiles-shielding water-sensitive intermediates in enzyme active site

Have Partial notes for BOTH

Chapters 1-2 and Chapter 3

for use in class tomorrow

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Review of Acid-Base ConceptsIonization of Water (1)

Water dissociates into hydronium (H3O+) and hydroxyl (OH-) ions H2O + H2O → H3O+ + OH-

(write H+ rather than H3O+ for simplicity)

H2O H+ + OH-

Equilibrium constant (Keq)Keq = [H+] [OH-] / [H2O]

[H20] = 55.5M Keqwater = 1.8 x 10 -16 M

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Ionization of Water (2)

H2O H+ + OH-

Since [water] (i.e. 55.5 M) changes little by

ionization , the equilibrium constant of water

(Kw) can be simplified :

Keq = [H+] [OH-] / [H2O]1.8 x 10 -16 M = [H+] [OH-] / 55.5M

Kw = [H+] [OH-] (Kw = ion product of water)

At 25°C, Kw is 1.0 x 10 -14 M2

Definition of Acid & Base

Acid = proton donor Base = proton acceptor

Conjugate Acid Conjugate Base

acid H+ + base

acetic acid H+ + acetateCH3-COOH H+ + CH3-COO-

ammonium ion H+ + ammoniumNH4

+ H+ + HN3

The above are conjugate acid-base pairs

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The pH Scale

• pH is defined as the negative logarithm of the concentration of H+

The pH of a solution is a measure of the concentration of H+

(Søren Peter Lauritz Sørensen, 1909)

Acid-Base behavior in Water

Note: Since the ion product for water (Kw) is constant

(i.e. 1.0 x 10-14 M2), the product of [H+] and [OH-] is always1.0 x 10 -14 M2, thus

as an acid is dissolved in water,

the [OH-] decreases and vice versa.

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pH values for some fluids

• Lower values are acidic fluids

• Higher values are basic fluids

M)

M)

milk

- Household bleach

- Seawater

, tears

, saliva

- Black coffee- Beer

- Red wine

-Cola,

- Lemon Juice-vinegar

Acid Dissociation Constants of Strong vs Weak Acids

• Strong acids and bases dissociate completely in water

HCl + H2O Cl- + H3O+

• Cl- is the conjugate base of HCl

• H3O+ is the conjugate acid of H2O

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Acid Dissociation Constants of Weak Acids

Acetic acid is a weak acid

• Weak acids and bases do not dissociate completely in H2O

Equilibrium constant = Ka = [H+] [A-] / [HA]

The equilibirum constant for the dissociation of a proton from an acid in water is called the acid dissociation constant, Ka.

The Henderson-Hasselbalch Equation

• Defines the pH of a solution in terms of:

(1) The pKa of the weak acid

pKa = -logKa = log 1/Ka

*pKa is pH at which an acid is half dissociated

pKa is a measure of acid strength

(2) Concentrations of the weak acid (HA) and conjugate base (A-)

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Figure highlights some of the major acute (short-term) effects on the body during exercise.

http://www.chemistry.wustl.edu/~edudev/LabTutorials/Buffer/Buffer.html

When Dr. Mohnen says “go”, start holding your breath.

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Titration curve of acetic acid

(CH3COOH)

• Titration curves are used to determine pKa values

Buffering Power: An acid-base conjugate pair resists changes in pH of a solution (i.e. it acts as a buffer). A weak acid has most effectivebuffering capabilityin +/- one pH unit of its pKa.

Fig. 2.12

Fig. 2.13

Titration curve of acetic acid made by adding acid equivalents

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Fig. 2.14

Equilibrium constant = Ka = [H+] [A-] / [HA]

*

**

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Pick up Handout on Chapter 3 Homework Problems from the book (on the front desk)

Titration curve for

phosphoric acid (H3PO4)

The phosphate buffer system contributes to

intracellular buffering

Phosphoric acid

Dihydrogen phosphate ion

Monohydrogen phosphate ion

Phosphate ion

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The pH of the blood is regulated primarily by the

CO2-carbonic acid-bicarbonate buffer system.

Human Blood plasma is ~pH 7.4

CO2

CO2

Blood plasma of mammals has a remarkablyconstant pH of 7.4

Physiological salinepH 7, 1 liter

(0.15 M NaCl)

Blood plasmapH 7.4, 1 liter

1 mL 10 M HCL

pH 2 pH 7.2

How???

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Bicarbonate Buffer System for Blood. Percentages of carbonic acid and its conjugate bases as a function of pH (pH of blood plasma ~7.4)

CO2 (Gaseous)Carbonic

acid Bicarbonateion

Carbonateion

Proteins (hemoglobin) & inorganic phosphate also contribute to intracellular buffering

(app)

[H2CO3* includes dissolved CO2 (i.e. CO2(aq)), H2CO3* is used to represent the two species]

*

Regulation of the pH of blood in mammals

Build up of H+ from the tissues

Alkalosis(e.g. hyperventilation)

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Why did the pH of your blood not decrease markedly when you held your breath at the beginning of class?

Due to the bicarbonate buffer system in the blood.

*In the bicarbonate buffer system, the equilibrium between carbonic acid and bicarbonate acts as a pH regulator.

*When [H+]rises (pH drops), the bicarbonate ion acts as a base and removes the excess hydrogen ions. Excess H2CO3

becomes dissolved CO2 can be removed during breathing.

Conversely, if the [H+] concentration falls (if the pH rises), more carbonic acid dissociates, replenishing hydrogen ions. Dissolved CO2 can be increased by breathing.

Questions?

Questions?

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STOP

Answers for 8/15/17 Thought of the Day

What is minimum amount of water each person requires per year for drinking, hygiene and growing food?

*1000 cubic meters (264,170 gallons) (2/5 of Olympic-size swimming pool). [723 gallons/day] (Scientific American, Aug 2008)

* the average American uses over 100 gallons of water per day (EPA, 2004)

Water is minimum amount of drinking water each person requires per year?

SAFE DRINKING WATER ACT 1974 – 2004: (EPA)

* 66% of the human body is water

* A person must consume 2.5 quarts (~2/3 gallon) of water per day from all sources (drinking, eating) to maintain health

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Notices and Reminders

Be sure to form study groups for this class. It is a proven method to do well in the class!

Due at Breakout session next week:Homework Chapter 1-2Practice QuizThought of the Day

Chapter 3 Homework Assignments(see handout will be given out on Friday, or see website)

Minimum standards for daily water intake are universally recognized and set at 2.5 – 3 liters per day (or approximately 85 – 101 fluid ounces).

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Undergraduate Research Opportunities in

biochemistry andmolecular biology/molecular genetics

See Dr. Mohnen

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