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Biochemistry Exam #2
Notes

Lecture 7: Carbohydrates
“Hydrates of Carbon”  composed of C, H, and O
Chemical formula = (CH2O)n
Polymers of monosaccharides
Functions include: energy storage, signaling, structure
Cellulose = polymer of glucose



Structural function of plants
Glucose added to each other by beta linkages

Starch = polymer of glucose





Potatoes, rice
Storage form of glucose = stores glucose in our bodies until we
need it
Our bodies can break it down
Glucose added to each other by alpha linkages
o C-O bond is axial

Starch and cellulose are different because of one stereogenic center
Glucose = monosaccharide







Cyclic form is most stable = open chain form in water is not
stable  form 5 or 6 member rings intramolecularly
Heterocyclic = all atoms in the ring are C except for one O
Alpha and beta D-glucose
Carbon #1 is called the anomeric carbon
Hydroxyl group attacks from the top = alpha D-glucose
Hydroxyl group attacks from the bottom = beta D-glucose

Bottom-most stereogenic center determines D or L



D is when OH is on the right
L is when OH is in on the left

More carbons = more stereocenters = more stereoisomers exist
Aldo vs
...
L
Pyranose (6 membered ring) vs
...
Free fatty acids
 Long Hydrocarbon chains, end with COOH
 Functions: fuel, building blocks for membrane lipids
 They are stored as triacylglycerols
 Unsaturated = at least 1 double bond
i
...

 Saturated = all single (sigma) bonds
 Zwitterionic = at physiological pH, COOH is deprotonated
(loses a proton), becomes negatively charged, and is neutral,
but slightly basic
 Even # of C  12 to 24
 Alpha carbon is the carbon next to the carboxylate carbon
2

Biochemistry Exam #2
Lecture 8: Lipids (continued)


NOTATION: #Carbons : # of Double Bonds

2
...
Phospholipids
 Amphipathic or amphiphilic
 Polar head and non-polar tail
 Interact with both water and organic solvents
 Formed from phosphoric acid, glycerol, fatty acids
 Exterior of the cell is water and interior is water
 Barrier between extracellular/intracellular is lipid-based
 Hydrophobic effect = hydrophobic tails are aggregated


Sphingosine backbone
i
...
Only 1 fatty acid (not 3)
iii
...
R group is typically choline
v
...
Can be a sugar moiety like glucose or galactose –
therefore can also be a glycolipid *??*

4
...
Steroids/Cholesterol
 Helps maintain membrane fluidity
 Not covalently bound – has at least 1 hydroxyl group that
interacts with phosphate of the phospholipid
...
response

Biosynthesis of Steroids



Estrogen, testosterone, cortisol
Cortisol is an analgesic = needed for pain, give corticosteroids which
reduces inflammation

If you don’t produced cholesterol, mess with integrity of bilayer, might
actually rupture the cell membrane
...
Temp at which this happens = Tm = depends on
length of HC chain
Longer chain = higher Tm because of more bonds = more
rigidity

Cholesterol
Composition




Bending at cis double bond
Decrease Tm because of unsaturation
Kinks caused by double bonds = favors packing = increases
fluid state

Permeability of Lipid Bilayers
High permeability = small hydrophobic molecules, small uncharged
polar molecules
Low permeability = larger uncharged polar molecules, ions


Pores across membrane help transport ions, amino acids,
vitamins, etc
...

*all important for signal transduction pathways
In lipid bilayer, proteins and ion channels sit across the membrane to
transport otherwise impermeable molecules into the cytosol

5

Notes

Biochemistry Exam #2
Lecture 9: Membrane Structure and Function
(continued)
MHC complexes = some peripheral proteins outside cell
...

Work in 3 ways:
o Change in protein conformation  opens channel pore
 regulates ion flow
o Action potential changes  voltage-gated channels
(Na, Ca)
o Binding of ligands  ligand-gated channels
 Ligand = substance that when it binds to the
channel it will open the channel
Distinguishing features of ion channels:
7

Notes

Biochemistry Exam #2
Lecture 9: Membrane Structure and Function
(continued)
o
o
o

Ion selectivity = regulation by pore side
Selectivity filter = group of amino acids in pore that
regulates what ions can go through
Ion channel gating = channels exist in “open” and
“closed” gates that open to a stimulus

Voltage-gated = sodium channels, calcium channels
Ligand-gated (EC) = tyrosine and kinase receptors, TCRs
Ligand-gated (IC) = calcium channel
Mechanically-gated = mechanical stress such as stomach muscles or
carotid arteries in neck region

Lecture 10 (Bose): Cell Signaling
Communication between cells to coordinate their behavior to benefit
organisms
One protein tells another protein to activate – continues – cascade

Components of cell signaling
Receptor: usually integral membrane proteins that are bound to the
plasma membrane or other organelles (ER, mitochondria)
Ligand: small molecule that binds to receptor
Ex: glucocorticoid receptor – glucocorticoid must bind to it
Agonist: a ligand that causes a biological effect
Ex: increased heart rate caused by adrenaline; when
adrenaline binds to beta receptors on <3, activates <3
Antagonist/Blockers: binds to receptor or prevents agonist binding
Ex: Lopressor is a beta-blocker; sits where adrenaline is
supposed to bind to increase <3 rate

8

Notes

Biochemistry Exam #2
Lecture 10: Cell Signaling (continued)

Notes

Elements of signaling pathways
1
...
Antigens, hormones, ligands
2
...
Nicotinic receptors, acetylcholine receptors
3
...
Signal transduction = generation of second
messengers  bind to protein, DNA causing gene
expression, metabolism, etc
...
CALCIUM is MOST IMPORTANT 2nd messenger
4
...
Initiation of cellular proceses
Ligand passes on messages to effector (example of a peripheral
protein)  effector relays info to 2nd messenger  this messenger
goes to diff
...
”
Examples of molecular swiches: Phosphorylation and GTP-binding
proteins
Activation by Phosphorylation:
Kinase = cause phosphorylation (“on”)
Phosphotase = ADP + Pi  ATP (“off”)
Activation by GTP/GDP-binding:
GEF (Guanosine Exchange Factor) = GDP  GTP (“on”)
GAP (GTPase Activating Protein) = GTP  GDP + Pi (“off”)
**does not involve phosphorylation – just protein swapping**
GDP = sits in pocket of protein so that the protein is inactive
GAP cleaves GTP
GDP = guanosine diphosphate

9

Biochemistry Exam #2
Lecture 10: Cell Signaling (continued)

Notes

Ion-channels
Voltage-gated cation channels



Activated by voltage-opening channel
Conduction of Na+, Ca++, and K+

Ligand-gated ion-channels


Ligands activate the channel

G-Protein Signaling Pathways
GPCRs = G-protein coupled receptors
G-proteins




guanosine binding protein
heterotrimeric (“3 different proteins” bc of 3 subunits)
three protein subunits = alpha, beta, gamma
o Alpha is the biggest subunit  also has intrinsic GTPase
activity, turns “off” GPCRs
o GDP binds to alpha subunit
o When you have GDP, GPCR is off/inactive

GTP bound = active
GDP bound = inactive
Hang out near plasma membrane/close to integral membrane protein
50% of drugs target GPCRs; 20% of top-selling drugs
When a ligand binds to GPCR  causes a conformational change 
GDP out and GTP in  activates alpha, beta, and gamma subunits 
relayed downstream  turn off by removing GTP and getting GDP in
the pocket again
**Calcium Pathway (IP3)**
Calmodulin (CaM)




Activated by Ca++ & changes conformation by binding two or
more Ca++
CaM activates CaM Kinases such as CaMKII  phosphorylates
CREB which is a transcription factor (protein expression)
CaMKII in cytosol
10

Biochemistry Exam #2
Lecture 10: Cell Signaling (continued)



Notes

PMCA activated by CaM  on cell wall, pumps Ca++ out of cell
using ATP = muscle contraction and relaxation
CREB forms your memory

**cAMP dependent activation pathway**
Revelant in cardiac function/skeletal muscle
Special GPCRs in <3 = beta receptors
AC = adenylyl cyclase = converts ATP to cAMP
cAMP activates PKA = protein kinase A
PKA activates ryanodine receptors to release Ca++ which activates
CAM
CAM activates TNN which causes contraction
To turn off:
PDE cleaves ester group on cAMP  now 5’-AMP
Without cAMP = no functions = relaxation
*important = phosphorylase inhibitors (caffeine)*
PKA
Regulatory domain and catalytic domain
Known as Ser/Thr kinase
C + R bound = not activated
cAMP binds to R domain, then C domain gets detached, both go to
activate different pathways
After GPCRs are activated:





Adrenergic receptor: fight or flight - <3 rate
Histamine receptor: immune rxn – gastric acid release
Muscarinic receptor: rest&digest – muscle contract – salivation
Serotonin antagonist: neurotransmitter release
o Activator: Prozac

11

Biochemistry Exam #2
Lecture 11: Cell Signaling 2

Notes

Protein kinase C


Activated by DAG and Ca++

Functions:






Cell growth and division
o Activation of c-jun, c-fos (oncogenes)
o Activation of ras pathway
o Activation of NF-kB
Smooth muscle contraction
Cardiac function
GI acid pump function

Receptor tyrosine kinase (RTKs)
Transmembrane receptors
Activated by ligand binding
Tyrosine side chains stick out because kinase is right next to it and
will phosphorylate the side chain
Kinase domains – phosphoryl groups
Peptide group factors are ligands
Dimerization of RTKs leads to autophosphorylation of RTKs
Absence of ligand = RTK is a monomer
Ligand binds to monomer = forms dimer
When dimerized, so close that kinases start phosphorylating at the
same time = self or cross phosphorylation
Once you have outside domains getting phosphorylated, allows for
docking of proteins  get effector protein
SOS = son of sevenless  without this you cause cell division and cell
growth
Ras – Superfamily of GTPases
Ras is monomeric and has intrinsic GTPas activity
Anchored close to the plasma membrane
When Ras is bound to GDP = off
Activates MAP kinase
TWO TYPES:
Ras that needs GAP activity, RAS that has intrinsic GAP activity
12

Biochemistry Exam #2
Lecture 11: Cell Signaling 2 (continued)

Notes

Ras ultimately activates ser/thr kinases (PKA)
Most important cascade is the MAPK pathway  signals downstream
phosphorylation
MAPKKK = already have kinase and then phosphorylate two more;
phosphorylating in three different places
Now known as Raf
Raf is also a kinase because its KKK
-takes MAPKKK and converts it into activated MAPKK then turns it into
activated MAPK (Erk)
-Erk goes into nucleus and activates proteins and transcription factors
**MAPK Pathway**
1
...

3
...

5
...
Activation of CREB = neurotransmission, immune
response, inflammatory response
b
...
Activates Elk = learning and memory
d
...
MAIN FXN = case more cell growth and division = Cyclin
D1

Mutated Ras  cannot turn itself off, therefore keeps activating and
sending signals which activates all downstream proteins
-uncontrolled cell growth and division from Erk = cancer
Cross talk between Ca++ release and RTKs
Signaling molecules: IP3R, PLC, SERCA
**Cross-Talk/N-FAT Pathway**
Ligand binds to RTK
Activation of PLCy  formation of IP3  release of Ca and increase of
cytosolic Ca  activates calcineurin  NFAT moves to nucleus 
activates gene transcription
13

Biochemistry Exam #2
Lecture 12: Cell Signaling 3

Notes

**AKT Pathway**
Initiated by tyrosine kinase pathways
Important for glucose metabolism (diabetes)
AKT is activated by RTK (insulin growth factor receptor) and ligands
(insulin or IGF)
Phosphorylation of IGF
Activating of PI-3 Kinase  phosphorylates PIP2 to PIP3
PIP3 dephosphorylated by PIP2 by PTEN
PIP3 activates PDK1  mediated phosphorylation of AKT to AKT-P
AKT amplifies signal using various messengers
o
o
o

AS160 – causes GLUT4 (glucose transporter) to bind to
PM to increase glucose transport
NF-kB – increase cell survival
mTOR (major target of rapamycin)
 increases cyclin D activation  increase in cell
proliferation
 ani-apoptotic Bcl-2  promotes growth and
differentiation
 downstream regulation such as lipid synthesis,
ATP production, O2 levels

MAIN FXNS: increasing glucose transport, increase cell survival,
promote cell growth and proliferation

Nuclear Receptors (NRs)
o
o
o
o

bind to DNA and cause transcriptional changes
found in cytoplasm or nucleus
ligands are steroid hormones, thyroid hormones, retinoids,
vitamin D  hydrophobic
short term and long term effects (mainly long term)

NR family
Fenofibrate = targets PPAR alpha
Actose acts on PPAR gamma (glucose synthesis)
Estrogen = contraceptives
Retinoid = cirrhosis
Thyroid = Synthroid/Levothyroxine
Mineralcorticoid = aldosterone antagonist = Spironolactone
Anti-inflammatory = gluticocorticoid = pain & inflammation
14

Biochemistry Exam #2
Lecture 12: Cell Signaling 3 (continued)

Notes

NRs composed of 2 domains: Ligand binding and DNA binding
Ex: steroid binds  conformational change

Corepressors will decrease gene expression *??*
Co-activator proteins = try to prevent ligand from dissociating, thus
increasing gene expression

Lipid signaling pathways
Eicosinoids = lipids made from oxidation of 20C fatty acids
AA is most common precursor in humans
o
o

not stored in cells – activated by physical/chemical stimuli
produced by phospholipids

AAs go downstream and produce prostaglandins

1
...
AA converted to:
a
...
NSAIDs inhibit COX = therefore inhibits PGE2
and you feel less pain
1
...

ii
...
PGE2 = pain, vasoconstriction, gastric
secretions
2
...
PGH2  TXA2 by thromboxin synthase
a
...
Leukotrines (LTs) by lipoxygenase (LOX)
i
...
Neutrophil migration
ii
...
Bronchoconstriction = if you have
asthma, you have more LTD4, get
montelukast/singulair

15



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