Molecules of Living Systems
the chemical properties of the living
state
The
structure of biological molecules and how their
shape
determines
the roles
they play in the complex chemical processes of life.
Even the most complicated biological molecules can be divided
into smaller and smaller
functional groups.
The chemicals of life...
ELEMENTAL
CHEMISTRY
- elements
are substances composed of
atoms all
with identical number of protons…
- can’t be reduced to simpler substances by
normal chemical means
-
only
30
of
92
elements
COMMONLY OCCUR IN LIVING SYSTEMS...
- and
99%
of LIVING MATTER is made of...
C H O
P S N
all have
low atomic numbers,
table of
valance electrons
& are easily reactive &
form
covalent bonds* covalent
bond figure
|
Molecular composition of cells...
|
|
Water (H2O)
 |
70
% |
|
Inorganic ions (Na, K, Cl, PO4) |
1
% |
|
Small molecules (aa’s, sugar, nucleotides) |
5
% |
|
Macromolecules (protein, n.a., etc) |
24
% |
chemical composition of bacteria*
-->
JMM |
Biomolecules, Weak Forces, & Design of Metabolism
The properties of chemcials that are
esssential for ALL CELLULAR PROCESSES and
may have lead to the
EMERGENT PROPERTIES of molecular systems
(akin to life)
BIOMOLECULES...
mostly
carbon compounds
are found in living systems…
WHY
Carbon
?
(carbon
skeletons)*
-
easily forms 4 covalent bonds…
thus makes many small
biomolecules
atom's electronegativity is able to attract electrons from other
atoms:
nonpolar covalent bond:
equal electronegaivity/equal
sharing of e-'s
[C-C, C-H]
polar covalent bond:
unequal electronegativity
results in unequal charge distribution
within an electrically
neutral molecule
[water -
fig 2.5*].
-
allows 3-D shapes that may evoke
biological activity
based upon conformation
-
carbon favors
great
chemical reactivity…
-
Carbon covalents interacts with common
chemical functional
groups*
Functional Groups:
groups of atoms, acting as a unit, that give organic molecules
their physical properties,
chemical
reactivity, & solubility
in aqueous solutions.
In bio-molecular chemistry, the concept of
functional groups is useful,
as a basis for classification of large numbers of compounds according
to their chemical properties and reactivity.
|
|
most
functional groups possess electronegative atoms on C's
[ C-
O, N, P, S
] |
|
key bonds are :
esters C-O-C*
&
amines &
amides -C-N-* |
| most are
ionizable at physiological
( pH 6.6 to 7.4) read
pages 47-49* |
| |
 |
|
Consequences of substitution with a functional group* |
|
|
Let's look at
small
Biomolecules made
via Chemical Bonds & Functional Groups
Major groups of small biomolecules...
the monomers -
mcb fig 2.13* -
make polymers
a.
SUGARS
-
compounds
with repeat formula of... [CH
2O]
n
aldoses vs. ketoses*,
rings*, a & ß-links*, isomers:
glucose vs. galactose*
 *
glucose
+
glucose = mono-,
disaccsaccharides*, tri-,
polysaccharides*
&
long chain polymers of monosaccharides
b.
FATTY ACIDS
-
saturated
FA* vs unsaturated*fatty acids*
[Table 2.4*]
form
triacylglycerols*
=
lipid - 3 chain hydrocarbons*
3
lipids &
animal
fats
*
and
phospholipids* of membranes
(mcb fig 2.20*)
easily self-assembly into aggregates*:
soap
micelles &
bilayers*
&
fluidity*
also steroid & cholesterols* (4-ring skeleton)
are lipids because they're
insoluble
in
membranes (mcb fig 1.13)*
mcb5e fig 18.6 derivatives
end 6
Biological Activity
&
the Shapes of Biomolecules |
 |
Structural Chemistry:
orientation of covalent bonds in space.
molecular configuration
results in specific bond angles and molecular geometry
|
methane
CH4
109.5o - a tetrahedron
with free rotation
formaldehyde
H2C=O
120o - same plane
with no free rotation |
fig
2.3* |
| |
|
| one key
to shape is the ASSYMETRIC CARBON... |
| a carbon atom bound to 4 dissimilar atoms in a
nonplanar configuration (tetrathedron) |
results in 2 different spatial orientations
--> producing
CHIRAL molecules...
ones that are mirror images of each other (i.e., optical or stereoisomers) |
|
|
ENANTIOMERS* molecules
that are non-superimposable mirror images of one another
called
Stereoisomers...
the two molecules are not equivalent or identical, and
have
2 molecular orientations
or mirror images
an optically active,
CHIRAL*,
is not superimposable
on
its mirror image
chiral animation
stereoisomers
may have mostly
identical chemical properties,
but
often rotate plane of
polarized light
via different angles.
LEVOROTARY*
(L) -
rotates light
left
(-
negative optical rotation)
DEXTRORTATORY
(D) - rotates light
right
(+
positive optical rotation)
and likely have different BIOLOGICAL ACTIVITY...
Parkinson's
Disease & dihydroxyphenylalanine
=
L-DOPA
figure*
"awakenings"
Biological activity...
is catalytic ability of molecules to do work
There are
2 properties of biomolecules, which
contribute to a molecules
unique FITNESS
for Biological Activity &
the Living State
*
A.
CONFIGURATION: spatial arrangement of atoms in molecules
about bonds...
configuration can’t be inter-converted w/o breaking bonds
covalent examples of configurations:
isomers... based upon covalent bond configurations [glu
vs. gal]*
each has different chemcial properties
and those due especially to
COVALENT
DOUBLE BOND*
isomers...
built upon
double bonds C=C
Cis = Trans*
fix atoms above & below plane of molecule &
restricts free rotation, thereby fixing 3D shape
in space.
maleic (cis) vs. fumaric (trans)
11-cis-retinal
vs. 11- trans-retinal
Biological Activity
& the
Shape of Biomolecules
continued...
|
B. CONFORMATION
[or shape] - surface
outline
or
contour |
3-D orientation
of chemical groups that are free
to assume different positions in space without breaking any bonds
- do primarily to...
FREE ROTATION of atoms about a single chemical bond
WEAK NON-COVALENT FORCES hold atoms in spatial
arrays |
 |
- consequences
of conformations...
different isomeric
shapes (forms) of molecules can exist,
only one
of which may be
biologically active
(others aren't)
ENZYMES can distinguish between
biologically active forms
(isomers)
based
upon the "SHAPE" of that isomer |
|
|
due to
Weak Molecular Forces of Life...
IONIC bonds*
attraction between cation
(+) & anion (-);
no fixed geometry for electrostatic field
is
uniform in all directions; readily soluble with polar water
[Na+,K+,Ca+2,Mg+2,Cl-]* |
DIPOLES* attractions via asymmetrical,
internal distribution of charges in a
molecule,
which has no net
charge (opposite poles +/- attract) |
DISPERSION*
(van der Waal’s) Forces- electrostatic
interaction between orbitals of 2 atoms that
generates transient dipoles that attract/repel; results is cohesion between
non-
polar molecules that don't form H-bonds mcb fig 2.10 important in 3-D shapes |
HYDROPHOBIC Interactions*
- repulsion of electrostatic dipoles of water by
non-polars-
"fatty-hydrocarbon" groups self assembly
- "like dissolves like*" |
HYDROPHILIC Interactions* - substances that dissolve readily in water (ions & polar molecules)
water, as a
dipole, surrounds & solubilizes a solute molecule |
HYDROGEN
bonds*
[fig] - electrostatic attraction between
H of one atom
& pair of non-bonded
e-’s on
an acceptor group; linear directionality.
O-H &
N-H with
O- & N-
see 2.6a |
|
Non-covalent Electrostatic Interactions*...
(in
the 10-150 cal/mol range) |
Covalent & Weak Molecular Forces of Life ...
|
TYPE of BOND |
ENERGY (Kc/mol) |
TYPE of INTERACTIONS |
ENERGY (Kc/mol) |
|
SINGLE COVALENT BONDS |
NON-COVALENT BONDS |
|
O - H |
110 |
IONIC BONDS |
1.0 - 5.0 |
|
H - H |
104 |
HYDROGEN BONDS |
1.0 - 2.0 |
|
C - H |
99 |
VANDER WAALS |
0.1 - 1.0 |
|
C - O |
84 |
HYDROPHOBIC |
0.1 - 1.0 |
|
C - C |
83 |
 |
|
S - H |
81 |
|
C - N |
70 |
|
C - S |
62 |
|
DOUBLE BONDS |
|
C = O |
170 |
|
C = N |
147 |
|
C = C |
146 |
fig 2.6 relative
bond energies*
Biological Design or
How
Shape &
Weak Molecular Forces may
build
FORM
Tensegrity-
(tensional integrity) where a structure maintains stability under tension;
it
may be
an architectural principle
that helps contributes to
biological
form & shape.
a
basic question of the living condition has always been (???)
How do individual groups of molecules assemble
themselves within living organisms?
Is there
a
fundamental principle that guides biological
organization ?
obviously some common-universal rules of molecular assembly may exist…
one sees recurring patterns of
spirals,
triangulated
forms, & pentagons
in
everything from
crystals to
proteins,
viruses to
plankton, paramecia to protozoa.
...Is there some PRINCIPLE
of SELF-ASSEMBLY...
molecules join to form larger & more stable structures,
often
with new & non-predicted
properties
or
emergent properties…
macromolecules
->
organelles
->
cells
->
tissues
->
organs
maybe the answer lies in the principles of
TENSEGRITY...
the application of general architectural principles to biomolecules & living systems
|
TENSEGRITY
defines the mechanical rules of how structures are stabilized
by balancing forces of internal
tension and
compression
[tensional integrity].
|
TENSEGRITY
may be a fundamental aspect of
SELF-ASSEMBLY -
an architectural system, mechanically stable, yet dynamic,
where the forces of tension and compression balance.
"tension
& compression are eternally complementary elements in any structure"
|
Geodesic
Domes
(Buckminster
Fuller)
an entire structure distributes its mechanical stresses...
on frames of rigid struts connected into
triangles,
pentagons,
or hexagons…
each of which bears
tension or
compression. |
 |
|
 |
Prestress Structures
(Ken
Snelson
pic) -
struts that bear
tension are distinct from ones bearing
compression.
Compression members can provide rigidity while remaining separate,
not touching one another, held in stasis only by means of
tensed wires. |
click on pic*
|
In both of these structures
tension
is continuously
transmitted across all
structural members.
|
|
|
some toy models - models*
and
picture
and
straw structures |
Tensegrity in Biological Systems ???
Organismal Level
(a crude example...)
bones
are the
compression struts and
muscles, tendons,
&
ligaments
are the
tension bearing wires
Cell
(1970’s view)… membrane bounded viscous gel (molasses filled balloon)
today's...
cytoskeletal*
microtubules awash in a viscous gel,
tensed by microfilaments, surrounded by
membrane
fluorescent picture of cytoskeleton
cytoskeletal elements
cytoskeletal
elements as
the
microtubules... may act as
compression "girders";
and
microfilaments exert
tension, pulling all a cell's parts toward nucleus
►
the Cytoskeleton then may
be a
hard-wired molecular system that stabilizes
cell form & shape, according to the
architectural principles of tensegrity?
Biological
Tensegrity
suggests
-
that the structure of cell's
cytoskeleton can be changed by altering
the balance of physical forces transmitted across the cell’s surfaces.
for example: cultured cells on glass
[flat]
vs. a flexible surface [round]
Donald Ingber’s Tensegrity Model of a
Cell*
&
'Architecture of Life' by Don Ingber
Tensegrity further suggests –
Since many
enzymes and other substances that control protein synthesis, energy
conversion, & growth in the cell are physically
immobilized upon the cytoskeleton,
changing
the cytoskeletal geometry & mechanics
may affect biochemical reactions
& even alter the genes, which
may be activated & thus proteins may be made.
mcb fig 6.5
Binding a signal molecule (or
mechanical stress) to a receptor, which traverses a cell
membrane into a cell, MAY CAUSE conformational changes at the opposite end of
the receptor, which may then trigger a cascade of molecular restructuring inside
a cell, including reorientation of the cytoskeleton.
cellular mechanotransduction*
SELF-ASSEMBLY of molecules into organelles
and/or cells into tissue
is
not much different from self-assembly of atoms
into compounds.
The shape a molecules assumes is characteristic of the way
the structure as a whole will behave in 3-D space, and maybe
cells respond in a similar way according to rules of
Tensegrity
µ
Fully triangulated
tensegrity structures, once self assembled,
may have been selected for through evolution, because of
their
structural efficiency, their high
mechanical strength, &
minimal use of materials.
|
Tensegrity may be the most
economical and
efficient way to
build cell structure. |
SUMMARY:
a few fundament |
