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MCB

 102:  
Survey  of  the  Principles  of  Biochemistry  and  
Molecular  Biology

Welcome!
MCB  102:  
Survey  of  the  Principles  of  Biochemistry  and  
Molecular  Biology

0.5  µm 3  µm 5  µm

Bacteria/archaea Animal  cell Plant  cell

Compartments:  Lipid  membrane  separate  cell  components  from  surrounding  environment.


Also,  separates  different  processes  from  each  other  inside  the  cell.
Genetic  code:        DNA  contains  all  the  information  (code)  required  to  make  a  living  organism.
Proteins:                          Encoded  by  DNA.  Performs  all  the  tasks  required  for  a  living  organism.
Energy:                               Required  to  power  reactions  and  other  cellular  processes
Course  Aim
Help  guide  you  through  the  process  of  learning  the  
fundamental  principles  of  cellular  life
Part  1  -­‐ Biomolecules Part  2  -­‐ Metabolism Part  3  – Molecular  Biology

Prof.  Davies Prof.  Miller Prof.  Ingolia

Structure  of  biomolecules.   Anabolism  and  Catabolism.   Transcription  and  Translation.  


Focus:  How  order  and   Focus:  Chemistry  of  cellular   Focus:  How  the  code  
properties  of  amino  acids   reaction  used  to  obtain   contained  in  DNA  is  
determine  the  function  of   energy  and  the  basic  building   converted  to  proteins  
a  protein blocks  of  biomolecules
MCB  102:  
Meet  the  GSIs

King  Cada Shawn  Costello Brittany  Daws Chandra  


Greenberg

Albert  Lee Erika  Lopez-­‐Alfonzo NasimaMayer


Overview  of  Today’s  Class

Introductions

Course  policy

Questions  and  queries

MCB102  Part  1:  The  nanoscale


Prof.  Karen  Davies  – Structural  Biology
Prof.  Karen  Davies  – Structural  Biology
We  study  how  proteins  interact  in  situ  to  execute  cellular  functions
Oxidative  phosphorylation ATP
ADP  +  Pi
NADH
NAD+
Mitochondria

H+
Succinate
2H2O
O 2 H+
H+ H+
H+
matrix
UQ UQ

cristae  space
H+
H+ H+ Cytochrome   + H+ H+ H+
H H+
H+ H+ C H+ H+ H+
H+ H+ H+ H+
Complex  I Complex  III Complex  II Complex  IV Complex  V
NADH   Cytochrome  C   Succinate   Cytochrome  C   ATP  
dehydrogenase reductase dehydrogenase oxidase synthase

Photosynthesis  – light  reaction ADP  +  Pi


Cyanobacteria

Light ATP
H+ NADPH
Light
H+ NADP
H+ H+ Fd
stroma FNR H+
PQ

lumen +
Plastocyanin
H+ H+ H
O2   H+ H+ H+ H
+
2H2O H+ H+ H+
H+
Photosystem   Cytochrome   Photosystem  I ATP  
II b6f synthase
Prof.  Karen  Davies  – Structural  Biology
We  study  how  proteins  interact  in  situ to  execute  cellular  functions

ATP  Synthase
IVA
IVB

III2
I1
Respiratory  Chain  
Mitochondrion Supercomplex
Prof.  Evan  Miller  – Central  Metabolism
Prof.  Evan  Miller  – Central  Metabolism
Prof.  Nick  Ingolia – Molecular  Biology
Prof.  Nick  Ingolia – Molecular  Biology
Prof.  Nick  Ingolia – Molecular  Biology
MCB  102:  
Meet  the  GSIs

King  Cada Shawn  Costello Brittany  Daws Chandra  


Greenberg

Albert  Lee Erika  Lopez-­‐Alfonzo NasimaMayer


MCB  102:  
GSI  – King  Cada
A.  King  Cada
Molecular  &  Cell  Biology,
James  Hurley/  
Carlos  Bustamante  Labs
Discussion  sections:
Wed  12-­‐1  pm,  130  Dwinelle
Wed.  2-­‐3  pm,  242  Dwinelle

Office  hours:
Tuesdays,  11-­‐12  PM,  B1  Stanley    

I  am  interested  in  understanding  how  proteins  control  the  shape  of  membranes.  My  
research  focuses  on  determining  how  a  set  of  proteins  called  ESCRT  releases  HIV  from  the  
host  cell.

My  research  mostly  aligns  with  MCB102  part  I  which  explains  the  fundamentals  of  protein  
structure  and  function.  
MCB  102:  
GSI  – Shawn  Costello
Shawn  Costello
Biophysics,  
Susan  Marqusee  Lab

Discussion  sections:
Tuesday,  9-­‐10  am,  20  Wheeler
Friday,  10-­‐11  am,  B56  Hildebrand
Office  hours:
Friday,  9-­‐10  am,  Stanley  Hall  B1
Nascent  Chain

I  am  interested  in  how  proteins  fold  during  translation.  My  goal  is  to  develop  
techniques  that  will  allow  us  to  monitor  the  structure  of  proteins  as  they  are  translated  
by  the  ribosome,  and  to  investigate  how  this  process  prevents  protein  misfolding.

My  research  most  closely  aligns  with  the  first  part  of  MCB102  covering  protein  structure,  
energetics,  and  function.
MCB  102:  
GSI  – Brittany  Daws
Brittany  Daws
Molecular  and  Cell  Biology/  
Chemical  Biology,  
Evan  Miller’s  Lab
Discussion  sections:
Monday,  9-­‐10am,  Dwinelle 234  
Monday,  10-­‐11am,  Wheeler  108
Office  hours:
Monday,  2-­‐3pm,  1  Lewis  Hall

In  general,  I  am  interested  in  how  electrical  activity  within  a  single  cell  can  act  as  a  
molecular  signal.  To  do  this  my  lab  works  on  developing  systems  where  we  can  visually  
measure  the  electrical  changes  across  a  membrane,  especially  in  nerve  cells  for  example.  

My  research  most  closely  aligns  with  the  2nd part  of  MCB102  covering  metabolism.
MCB  102:  
GSI  – Chandra  Greenberg
Chandra  Greenberg
MPH  Student
School  of  Public  Heath

Discussion  sections:
Friday,  9-­‐10  am,  234  Dwinelle
Friday,  12-­‐1  pm,  3  Evans
Office  hours:
Wednesday,  10-­‐11  am,  GPB  105 Clostridium  difficile

I  am  interested  in  infectious  disease  epidemiology,  health  disparities,  and  


immunology.

My  research  most  closely  aligns  with  the  third  section  of  the  course  covering  
molecular  biology.  
MCB  102:  
GSI  – Albert  Lee
Albert  Lee
Molecular  and  Cell  Biology,  
Jay  Groves  Lab

Discussion  sections:
Monday,  1-­‐2  pm,  385  LeConte
Monday,  2-­‐3  pm,  243  Dwinelle
Office  hours:
Tuesday,  2-­‐3  pm

I  am  interested  in  the  biochemistry  and  biophysics  of  enzymatic  reaction  on  
the  membrane.  Specifically,  how  spatial  confinement  can  influence  the  
reaction  kinetics  of  peripheral  membrane  proteins.

My  research  most  closely  aligns  with  the  first  part  of  MCB102.
MCB  102:  
GSI  – Erika  Lopez-­‐Alfonzo
Erika  M.  López-­‐Alfonzo
Molecular  and  Cell  Biology
Andreas  Martin  Labs

Discussion  sections:
Thursday,  9-­‐10  am,  103  GPBB
Thursday,  10-­‐11  am,  103  GPBB
Office  hours:
Wednesday,  1-­‐2  pm,  1  Lewis  Hall

I  am  interested  in  studying  the  process  of  protein  degradation  by  the  26S  proteasome.  
Specifically,  I  want  to  elucidate  which  substrate-­‐proteasome  interactions  are  required  for  
commitment  to  degradation  of  a  substrate.

My  research  interest  align  best  with  the  first  part  of  the  course,  where  we  talk  about  
protein  structure  and  enzyme  kinetics.  
MCB  102:  
GSI  – Nasima Mayer
Nasima  Mayer
Endocrinology  Program
Mina  Bissell  Lab

Discussion  sections:
Monday  12-­‐1pm  224  Wheeler
Monday  3-­‐4pm  242  Dwinelle
Office  hours:
Mondays  4  -­‐ 5pm,  105  GPB

I  am  interested  in  understanding  consequences  of  estrogen  receptor signaling  in  normal  
ER-­‐𝛼+  luminal cells  that  is  distinct  from  malignant  cell  lines.  

My  research  most  closely  aligns  with  the  second  part  of  MCB102  which  focuses  on  
metabolism.
MCB  102:  
Course  Organization
Contact  components:
Lectures:     3  hours  /  wk
11:10  am  to  12  noon,  Dwindle  Hall  155
Monday,  Wednesday,  Friday

Discussions:     1  hours  /  wk


Must  sign  up  to  one  discussion  section
Only  attend  the  discussion  section  you  signed  up  for
Discussion  sections  start  Monday  22nd January

Optional  components:
Office  hours:     9  hours  /  wk
Attend  if  you  are  struggling  with  concepts  or  have  specific  
questions
Prof.  office  hours        2  hours/wk only  during  section  of  Prof.  
GSI.    office  hours        7  hours/wk throughout  course
MCB  102:  
Office  Hours  -­‐ Instructors
Instructor  Name:  Karen  Davies
Part  1

Office  Location:  458  Donner Laboratory


Office  Hours  (Time  and  Day):  
Thursday  11  -­‐ 12  pm;  Friday  1:30  -­‐ 2:30  pm
E-­‐mail:  karen.davies@berkeley.edu

Instructor  Name:  Evan  Miller


Office  Location:  227  Hildebrand  Hall
Part  2

Office  Hours  (Time  and  Day):  Thursday,  3-­‐4  pm;  


Friday  3-­‐4  pm
E-­‐mail:  evanwmiller@berkeley.edu

Instructor  Name:  Nicholas  Ingolia


Office  Location:  231  Barker  Hall
Part  3

Office  Hours  (Time  and  Day):  Tuesday,  3-­‐4pm;  


Friday,  3-­‐4pm
E-­‐mail:  Ingolia@berkeley.edu
MCB  102:  
Office  Hours  -­‐ GSIs
Monday
2  – 3  pm,  Brittany,  1  Lewis  Hall
4 – 5  pm,  Nasima,  105  GPB  
Tuesday
11  – 12  pm,  King,  B1  Stanley  Hall
2  – 3  pm,  Albert,  458  Donner
Wednesday
10  – 11  pm,  Chandra,  105  GPB  Hall
1  – 2  pm,  Erika,  1  Lewis  Hall  
Thursday
No  GSI  office  hours

Friday
9 – 10  am,    Shawn,  B1  Stanley  Hall
MCB  102:  
Course  Timetable

9:00  am Monday Tuesday Wednesday Thursday Friday


Dis: 101 Dis:  107 Dis:  110 Dis:  112
Shawn
10:00  am Brittany   Shawn Erika Chandra
Dis:  102 Dis:  111 Dis:  113
Chandra
11:00  am Brittany Erika Shawn
Class King Class Davies  (Part  I) Class
12:00  pm
Dis:  103 Dis:  108 Dis:  114
Nasima King Chandra
1:00  pm
Dis:104
Albert Erika
Albert
2:00  pm Davies (Part  I)
Dis:  105 Dis:  109
Brittany
Albert King
3:00  pm Miller  (Part II)
Dis:  106 Miller (Part II)
Ingolia (Part III)
Nasima Ingolia (Part III)
4:00  pm
Nasima
5:00  pm
MCB  102:  
Examinations

30% Midterm  #1 25th Feb. 155  Dwinelle 7-­‐9pm


100  GPB

30% Midterm  #2 3rd April 155  Dwinelle 7-­‐9pm


2050  VLSB
30% Midterm  #3 14th May TBA.

10% Quizzes Best  5  of  6  tests  taken  in  discussion  sections

Exam  conflicts  
Must  notify  Professors  or  GSI  before  4th February
DPS  students
MCB  102:  
Review  Sessions

GSI
Exam  1  Review:  Friday,  February  22 from  5-­‐7pm
Exam  2  Review:  Monday,  April  3  from  5-­‐7pm
Exam  3  Review:  Friday,  May  10  from  5-­‐7pm  or  11-­‐12pm

Instructor
Exam  1  Review:  Friday,  February  22 from  11-­‐12pm
Exam  2  Review:  Monday,  April  1  from  11-­‐12pm
Exam  3  Review:  Wednesday,  May  8 11-­‐12pm  
MCB  102:  
Study  Aids

Textbook:   Principles  of  Biochemistry  7th Edition,  Lehninger

BCourse:   All  course  information,  lecture  slides,  problem  set  and  course  
announcements  will  be  distributed  through  the  bCourse site.  
You  are  responsible  for  reading  announcements  made  through  
the  bCourse website.  

Piazza:   Piazza  will  be  used  to  facilitate  group  discussion.  This  application  runs  
through  the  bCourse site.  Group  discussion  threads  are  moderated  by  
instructor  and  GSIs.  Posts  can  be  completely  anonymous  to  classmates.  
We  encourage  classmates  to  also  answer  posted  questions.
Please  use  Piazza  to  ask  questions  if  you  are  struggling  with  concepts  or  
problems.  Do  not  use  e-­‐mails  as  you  will  NOT  get  a  response.  
https://piazza.com/berkeley/spring2019/58258/home
MCB  102:  
Study  Tips
Participate  actively!

Come  to  lecture

Ask  questions:
-­‐ especially  in  discussion  section
-­‐ can  be  online/anonymous  using  Piazza
Answer  questions
-­‐ you  know  it  best  when  you  explain  it
-­‐ answering  questions  on  Piazza  can  be  a  great  tool  to  
assess  your  knowledge
Reading  and  practice  problems
-­‐ read  assigned  chapters
-­‐ complete  practice  problems

Exams  will  test  application  of  knowledge  as  well  as  contents
-­‐ don’t  just  memorize  slide,  work  to  understand  and  apply  contents

If  you  are  struggling,  attend  office  hours!!


MCB  102:  

Any  Questions  or  


Queries?
MCB  102:  
Part  1  – Prerequisite  Knowledge
Prerequisite  courses:          Chem.  1,  Chem.  3A-­‐3B,  Biol.  1A  &  1AL

Architecture  of  Cells


Properties  of  water
Functional  groups
Carbon  chemistry
Entropy

Advised  Reading: Chapter  1   1.1  p3-­‐6,  Box  1-­‐1


1.2  p12-­‐13
1.3  p21-­‐27
Chapter  2 2.1

Advised  Problems:       Textbook:  Chapter  1:  Q1  &2,  


The  Nanoscale
Class  Aim:  Provide  an  appreciation  of  how  small  a  cell  is  and  how  the  
movement  of  a  single  charged  atom  can  severely  affect  cellular  activities

1  inch  =  2.5  cm 1  yard 1  meter

Imperial  vs.  Metric  scales


In  science  we  use  the  metric  system
(it  is  a  lot  easier)
The  Nanoscale
Focus  of  
MCB102

http://learn.genetics.utah.edu/content/cells/scale/
The  Nanoscale

http://learn.genetics.utah.edu/content/cells/scale/
How  Small  is  The  Nanoscale
Osmotic  pressure
Osmosis  – red  blood  cells   P = icRT

Hypertonic Isotonic Hypotonic

H2O H2O

H2O

Concentrated
Saline  solution Pure  water
salt  solution

Saline  solution  =  0.15  M  NaCl


How  many  molecules  of  Na+ or  Cl-­‐ would  be  inside  a  cell?
How  Small  is  The  Nanoscale
Bacteria/
Red  Blood  Cell Epithelia  Cell
mitochondrion

2-­‐2.5   2  µm
1  µm
µm

18  
µm

Mitochondria
8  µm 11  
µm
11  µm
Volume  of  Cylinder  =  phr2 Volume  of  Cylinder  =  phr2
µm  =  10-­‐6 m
42  x  1.6  x  p x  (10-­‐6)3 11  x  11  x  18  x  (10-­‐6)3 0.52  x  2  x  p x  (10-­‐6)3
8.04  x  10-­‐187 m3
80.4   2178  x  10-­‐18  5  m3
2.178   1.57  x  10-­‐18 m3
1L  =  0.001  m3
8.04  x  10-­‐14 L 2.178  x  10-­‐12  L 1.57  x  10-­‐15  L
How  Small  is  The  Nanoscale
Bacteria/
Red  Blood  Cell Epithelia  Cell
mitochondrion

2-­‐2.5   2  µm
1  µm
µm

18  
µm

Mitochondria
8  µm 11  
µm
11  µm
Volume: 8.04  x  10-­‐14 L 2.178  x  10-­‐12  L 1.57  x  10-­‐15  L

Molecules mols
Avogadro’s  number  =   Molarity =   Liter
mols
6.022  x  1023 0.15  M

Molecules  in  a  ’cell’  =  Avogadro’s  number  x  Molarity x  Liter


How  Small  is  The  Nanoscale
Bacteria/
Red  Blood  Cell Epithelia  Cell
mitochondrion

2-­‐2.5   2  µm
1  µm
µm

18  
µm

Mitochondria
8  µm 11  
µm
11  µm

8.04  x  10-­‐14 L 2.178  x  10-­‐12  L 1.57  x  10-­‐15  L


8.04  x 0.15 x  6.022  x 2.178 x  0.15 x  6.022 x   1.57 x  0.15 x  6.022 x  
10-­‐14 x  1023 10-­‐12 x  1023 10-­‐15 x  1023
7.26  x  109  molecules 1.97  x  1011  molecules 1.42  x  108  molecules
7.26  Billion 197  Billion 142  Million
Molecules  in  a  ’cell’  =  Avogadro’s  number  x  Molarity x  Liter
pH  in  the  Cell
pH  =  -­‐log  [H+] pH  7.8

pH  4.7

pH  6.7-­‐6

pH  5.5
pH  7.0

pH  7.2
pH  in  Mitochondria
Cristae
Inner   Matrix  (pH  7.8)
membrane Outer  
Intracrista space   membrane
pH  7.4
ADP  +  iP
NADH
What  happens  when  a  single  Proton   ATP
NAD+ moves  across  the  membrane?
H+
Succinate
O2 2H2O
H+ H+ H+
H+
matrix
UQ UQ

cristae  space
H+
H+ H+ H+ Cytochrome C
H+ H+ H+ +
H+ H+ H H+ H
+
H+ H
+
H+ H+ H+
Complex  I Complex  III Complex  II Complex  IV Complex  V
NADH   Cytochrome c Succinate Cytochrome c ATP  
dehydrogenase reductase dehydrogenase oxidase synthase
Mitochondria
Mitochondrion Crista 40  nm

320  
nm

2  microns  x  1  
micron  diameter
150  nm
V  =  2p x  (0.5)2 x  (10-­‐6)3  x  103 V  =  0.32  x  0.15  x  0.04  x  (10-­‐6)3  x  103
0.00192  x  10-­‐15 L
1.57  x  10-­‐15 L 1.92  x  10-­‐18 L
Mitochondria
pH  =  -­‐log  [H+]

pH Mitochondrion Crista

significantly  change  pH  of  cristae  space


8 9.45 0.0012

Movement  of  just  one  H+  can  


Matrix  pH 7.8 14.9 0.018

Cristae  pH 7.4 37.6 0.046

pH  at   7 94.5 0.12


which  ATP  
synthase   6.5 299 0.37
activity  
inhibited 6 945 1.2

How  do  mitochondria  function  if  the  movement  of  one  proton  
drastically  changes  the  pH  in  the  cristae  space?
pH  in  Mitochondria
Cristae
Inner   Matrix  (pH  7.8)
membrane Outer  
Intracrista space   membrane
pH  7.4
ADP  +  iP
NADH
What  happens  when  a  single  Proton   ATP
NAD+ moves  across  the  membrane?
H+
Succinate
O2 2H2O
H+ H+ H+
H+
matrix
UQ UQ

cristae  space
H+
H+ H+ H+ Cytochrome C
H+ H+ H+ +
H+ H+ H H+ H
+
H+ H
+
H+ H+ H+
Complex  I Complex  III Complex  II Complex  IV Complex  V
NADH   Cytochrome c Succinate Cytochrome c ATP  
dehydrogenase reductase dehydrogenase oxidase synthase
The  Secretory  Pathway  in  the  Cell
Homework Lysosomes  
degrade  broken  
and  infectious  
things  by  
acidification

e.g.  Protons  
are  pumped  
into  the  
vesicle

How  many  protons  will  change  an  early  endosome  into  a  lysosome?
Typical  lysosomes  are  0.1-­‐1.2µm
Calculate  for  largest  and  smallest  
pH  =  -­‐log  [H+]
lysosome  e.g.  0.1  µm  and  1.2  µm
Avogadro’s  constant  =  6.022  x  1023
MCB  102:  
Part  1  – Prerequisite  Knowledge
Prerequisite  courses:   Chem.  1,  Chem.  3A-­‐3B,  Biol.  1A  &  1AL

Architecture  of  Cells


Properties  of  water
Functional  groups
Carbon  chemistry
Entropy

Advised  Reading: Chapter  1   1.1  p3-­‐6,  Box  1-­‐1


1.2  p12-­‐13
1.3  p21-­‐27
Chapter  2 2.1

Advised  Problems:       Textbook:  Chapter  1:  Q1  &  2,  

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