Unformatted text preview: CHEM 350: Introduction to Biological Chemistry
Brian Lee, Ph.D.
Ofﬁce: Neckers 146G or 324
Hours: 9:30am to 10:30am or by appointment
Textbook (required, U.S. edition only)
Fundamentals of Biochemistry, 3rd Ed., Voet, Voet & Pratt.
Study Guide (recommended)
Student Companion to Fundamentals of Biochemistry, 3rd Ed.
Tuesday 6:30 to 7:30 pm in Neckers 218
Thursday 5:00 to 6:00 pm in Neckers 410 Announcements
Undergraduate Research Opportunities
Research for credit (such as CHEM 396 or CHEM 496)
Student worker ($8.00 per hour) (http://www.siu.edu/~fao/jobs/)
Undergraduate Assistantships (http://www.siu.edu/~fao/jobs/)
McNair Scholars Program (http://www.siu.edu/~mcnair)
REACH Awards Competition (http://www.siu.edu/~reach/)
Summer Research Experiences for Undergraduates (REU)
Deadline for SIUC REU Program is March 7th
For other REU programs, search the National Science Foundation site:
Students must contact the individual sites for information and
application materials. NSF does not have application materials and does
not select student participants. A contact person and contact
information is listed for each site. Assignments
Read Chapter 9 Lipids and Biological Membranes
Chapter 9 Problems
Student Companion site for Voet, Voet & Pratt
http://bcs.wiley.com/he-bcs/Books?action=index&bcsId=4274&itemId=0470129301 Second Midterm Exam, Wednesday February 29th
Chapters 6 through 9 (All exams are cumulative)
No class on Monday, February 27th (no ofﬁce hours) Help Desk
Tuesday 6:30 to 7:30 pm in Neckers 218
Thursday 5:00 to 6:00 pm in Neckers 410 Lipids as Hormones: Intercellular Messengers
Steroids are carried by the
bloodstream to distant
tissues to regulate
kidney function, and
As oxidized derivatives of
sterols, steroids are more
polar than cholesterol and
bind to receptors on the
membrane surface. Steroid drugs have an
by inhibiting phospholipase
activity and reducing
prostagladin synthesis. Vitamin D production and metabolism
Photolytic action of UV light Vitamin D regulates
metabolism in kidneys,
bones and intestines. Rickets
Vitamin D deﬁciency
reduces uptake of
Ca2+ from intestines. Vitamin D toxicity
Excess vitamin D
leads to high Ca2+
seru m levels causing
kidney stones. Steroid synthesis:
Sterols and other isoprenoids
are synthesized by combining
isoprene units. Seven isoprene
units are used to make squalene,
a precursor for sterol. isoprene (5 carbons) Steroid synthesis:
Oxidosqualene cyclase creates
the four ring structure of the
the sterol precursor.
19 steps are required to
generate cholesterol from the
rearrangement of lanosterol. Other isoprenoids are built from isoprene units.
Hydrophobic tails make vitamins “fat soluble”. Protects against oxidative
damage to proteins and lipids.
No evidence that supplements of
vitamin E are beneﬁcial. Warfarin blocks activation of
prothrombin by vitamin K
dependendent carboxyglutamase Ubiquinone and Plastoquinone are electron carriers.
“Fat soluble” - found within the membranes of mitochondria
and chloroplast, necessary for ATP synthesis through
oxidative phosphorylation and photophosphorylation. Vitamin A1, precursors and derivatives Retinal is essential for vision (cis to trans).
Outside of the eye, retinoic acid acts as a
hormone to stimulate tissue repair, but can
also be teratogenic (causes birth defects). How do Lipids form Cell Membranes? Micelle
Bicelle Single tail lipids do not
co mpletely exclude water
in the bicelle structure.
Single tail lipids are not
useful for the lipid bilayer. Bicelle formed by
lipids with two tails
Cylindrical form leads
to better packing in
bilayer portion, but not
at the rounded ends.
Lipid Bilayer in a
liposome maximizes the
There are no rounded
ends as in the bicelle. Membrane dynamics
semisolid gel phase
Cellular activities are
optimal in the intermediate
liquid-ordered state. Bacteria vary the ratio of unsaturated lipids in the cell
membrane depending on temperature of environment.
Animals use the rigid cholesterol to decrease membrane
ﬂuidity and inhibit interactions between fatty acid chains.
This broadens the transition range between ﬂui d and solid.
high TM Motion of single
phospholipids in a bilayer: Flippase maintains
of inner and outer
faces of the cell
An untethered lipid
moves very rapidly.
Same applies to
“fat soluble” molecules Measurement of lateral diffusion
rates by ﬂuorescent recovery
after photobleaching (FRAP). Diffusion is dependent on
membrane ﬂuidity which varies
with the melting temperature of
the lipid components.
Higher melting temperatures are
indicative of more viscous lipids.
Ideal membrane is both ﬂui d-like
and solid-like. Fluid mosaic model of membrane structure Figure 9-25 Lipid Rafts - stable associations produce a microdomain Membrane proteins make up 50% of the cell membrane
Essential for function of cell membrane: transport, signaling,
adhesion, metabolism, photosynthesis, etc.
Integral membrane proteins associate with lipids in membrane
Hydrophobic interactions – lipid tails
Salt-Bridge and Hydrogen Bonding – head groups Polar and charged
residues internal Glycosylation – external domain Hydrophobic residues Transmembrane helix
3.6 res/turn 5.4 Å rise/turn
27-35 Å membrane depth
19-25 residues in helix Hydropathy plot shows region of hydrophobic residues Bacteriorhodopsin OmpF porin Cell Adhesion
Integral proteins that function in cell-cell interactions and cellextracellular matrix proteins interactions Lipid linked proteins can associate with membrane
Prenylation – farnesyl or geranylgeranyl isoprenoids Cysteine thiol linkage
X – alaiphatic Membrane Associated Proteins – lipid linked or head group
Myristoylation – N-terminal Gly residue
typically intracellular or organelle proteins
Palmitoylation – Cys residue linked to palmitic acid
cytoplasmic face of membrane – cell signaling
Glycosylphosphatidylinositol-linked protein (GPI anchor)
extracellular membrane bound proteins
Protein Lipid Protein targeting depends on amino acid sequence and linked lipids and carbohydrates The secretory pathway – directed by the signal peptide.
Signal Recognition Particle (SRP) - GTP driven recognition.
SRP Receptor on ER membrane, also GTP triggered.
Translocon – peptide insertion and TM embedding. The signal peptide at the N-terminus of a protein
directs the ribosome to the Rough ER for completion
of protein synthesis and insertion into the ER. SecY translocon in
a hydrophilic pore
in the membrane
to allow passage
of the nascent
chain into the
Sec61 is eukaryotes
performs the same
task for transport
into the RER. Hydrophilic
pore in the
middle of SecY
to pass through
the RER membrane What happens when a hydrophobic stretch of the
nascent peptide chain enters the pore? Model fo
of a hyd
bilayer o Cytoplasmic and mit
proteins are synthesized on
The signal peptide
directs the ribosome
to the Rough ER.
After synthesis and initial
processing, proteins are
transport from the
Rough ER to the
for ﬁnal processing.
From the Golgi,
proteins are transport
to the membrane for
insertion or secretion,
or to the lysosome,
or back to the Golgi or ER. Vessicle Fusion Clathrin coated vessicles Clathrin coated vessicles Nerve impulses are
the synapse between
neurons by small
released from vessicles
into the synaptic
cleft. SNARES mediate vesicle fusion with a membrane.
Q-SNARES – glutamine. R-SNARES – arginine. SNARES associate through
coiled-coil interaction Tetanus and botulinum
neurotoxins target SNARES
and prevent vessicle fusion
blocking release of
for signal transmission.
Q-SNARES on the target membrane surface include
SNAP-25 and syntaxin (green and red). R-SNARE on the
vessicle surface is synaptobrevin (blue). SNARE helices
are amphipathic. A seven residue repeat sequence:
a-b-c-d-e-f-g with a and d residues being hydrophobic.
Errata: The textbook mixed up syntaxin and synaptobrevin
in the legend to Fig 9-44 ...
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