Download Basic Acidic other polar amino acids

Metabolic Pathways
A --------- B ---------- C --------- D ---------- E
------------------------------------------------
usual direction of the reaction
In the body, metabolism involves a series of reactions that are linked together. This is similar to what is
shown above, with substrate A entering the pathway and it being converted, finally, to product E. Each
individual reaction is reversible but it doesn’t appear to be so because the product of one reaction acts as
the substrate of the following reaction and the reactions almost always proceeding from left to right under
normal circumstances.
Cascade: a special type of pathway (example is clotting) where the
product of one reaction
acts as an enzyme to make the next
reaction
occur. Here’s the blood clotting example:
This image is from:
http://neurobio.drexel.edu/GalloWeb/blood%20clotting%20cascade.gif
Law of Mass Action
This Law states that the concentrations of reactants and products influence the rate and direction of a
chemical reaction. Here’s a non-biological example:
This example will be discussed in some detail in class.
Gems
+
jeweler
--------------------
Jewelry
Gold
(reactant)
(product)
If LOTS of reactant is present <------------------------ You make lots of product
This direction is favored -
What happens ito the reaction if the following is occurring?
Reactant ----------------------------
If LOTS of product is present
Which direction is favored? ____________________________
A reversible reaction will come to equilibrium, with some product and some reactant always present
when the “dust clears”. At equilibrium, the rate of formation of products is equal to the rate of formation of
reactants.
How can we increase the rate of a chemical reaction?
1.
decrease the sizes of the molecules (they move faster so there is more chance of
collision and subsequent reaction).
2.
increase the concentration of reactant(s); the law of mass action tells us what will
happen!
3.
increase the temperature (molecules will move faster)
4.
decrease the activation energy; activation energy is an energy “hump” you have to climb
in order for a reaction to occur. In essence, you have to add energy before anything
happens.
5.
Add a catalyst, which functions to decrease the activation energy.
Biological catalysts are called enzymes. This is the only mechanism the body can
use to speed up reactions. Here’s an example of how much a difference enzymes
make:
Carbonic anhydrase can catalyze the following reaction:
H2O + CO2 <-----------
H2CO3
The reaction with the enzyme is 10,000,000 times faster than without it!
See Figure 2.21, page 55
Inorganic vs. Organic Molecules
Inorganic molecules do not contain C atoms; the exception is CO2 (carbon dioxide). Water and
salts are also examples of inorganic molecules.
Water’s Special Properties
1.
Universal solvent. Water molecules adhere to polar molecules. This occurs because of the
ability of water to disrupt ionic bonds and interact with polar molecules. Most of the molecules
found in the body are polar and thus like to interact with water, becoming solutes.
Figure 2.12, page 40
2.
High heat capacity. The temperature of water changes more slowly than that of other liquids. It
absorbs a lot of heat before it gets hot.
3.
High heat of vaporization. Water resists changing from a liquid to a gas.
4.
Water participates in some chemical reactions. Examples of this are dehydration synthesis
and hydrolysis, both of which we will discuss later.
5.
The body uses water to provide cushioning and protection (example, CSF around brain)
Salts and Electrolytes
The ionic bonds in salts are disrupted in water. The ions interact with the water molecules instead of
each other. Ions in water are called electrolytes, since they can allow the solution to carry an electric
charge.
Role of electrolytes in the body
Needed for almost all vital biological processes. Examples include:
1.
2.
3.
4.
5.
muscle contraction
nerve impulses
hormone release
blood clotting
fluid balance
The body regulates electrolyte concentrations via the skeletal system, kidneys and the digestive
tract.
Acids, Bases, and pH
•
Acids
•
•
•
donate a proton (H+) to a solution)
there are weak and strong acids
a strong acid dissociates almost completely in water
HCl ----------- H+ + ClHydrochloric
acid
There is little HCl remaining after it is added to water.
•
•
a weak acid doesn’t completely dissociate in water
H2CO3 ----------- H+ + HCO3Carbonic
Bicarbonate
Acid
ion
(exists in solution)
(exists in solution)
•
•
there are both weak and strong
bases usually release OH- (hydroxyl ions)
Mg(OH)2 ---------- Mg+2 + 2 OH(magnesium
hydroxide
This is
an antacid!)
Phillip’s Milk of Magnesia!
Bases
Then they hydroxide ions combine with hydrogen ions to form water, thus neutralizing the stomach acid!
2OH- + 2H+ --------- 2H2O
pH scale
Figure2.13 , page 42
In water H+ = 10-7M, OH- = 10-7M
pH= -log [H+]
pH = -(-7) = 7
Chemical Buffers
Physio intro 8
•
Help a solution resist a change in pH when either acid or base is added
•
composed of two related substances (a weak acid and a weak base)
•
the acid can donate a proton and the base can accept a proton
example:
The very physiologically important bicarbonate buffer system which we
will talk about more than once in this class. Cells produce acids like lactic acid
as a metabolic byproduct. The pH of the blood stays in a very narrow normal
range (7.35 – 7.45) primarily due to the ability of the bicarbonate buffer system to
neutralize these acids. If blood pH drops below 7.35 the person is said to be in
acidosis; if it rises above 7.45, the person is experiencing alkalosis.
Composed of H2CO3 and HCO3-; both species are present in the solution.
HCO3- can accept a proton:
HCO3- + H+ ------- H2CO3
H2CO3 can donate a proton:
H2CO3 ------ H+ + HCO3-
We will see later that there are also physiological buffers; this ends up buffering acid or base and
preventing the pH of the blood from changing too much if excess acid or base is produced. To do this,
the body changes the functioning of the lungs (breathing rate and depth) and/or kidneys (urinary
excretion). We will talk about this after we discuss the urinary system.
ORGANIC MOLECULES (overview Physio intro 10)
Large organic molecules are called macromolecules, composed of many smaller “building
blocks”.. Examples are the polysaccharides, nucleic acids, and polypeptides,
1.
Carbohydrates (carbs)
Figure 2.14, page 45, Physio intro 11A
Only1% of the body weight but SO important as a preferred fuel.
Contain C, H, O atoms
a.
Monosaccharides (simple sugars):
i.
pentoses such as ribose and fructose
ii.
hexoses such as glucose
b.
Disaccharides (simple sugars)
i.
Sucrose = the sugar we cook with
c.
Polysaccharides (large chains of simple sugars = complex carbs)
i.
Plant starch (the carbs in rice, bread, grains and beans)
ii.
Animal starch (glycogen, found in liver and skeletal muscle)
iii.
Cellulose (woods) protozoa in termite stomach digests the
cellulose; the termite can’t get nutrients otherwise!
How is a disaccharide (polypeptide) built up? ________________________
How is it broken down? _______________________ (See Fig 2.14, page 45!)
2.
Lipids Figure 2.15, page 47, and Table 2.2, page 48, and Physio intro 11A
15% of body weight; lots of non-polar (neutral) bonds so hydrophobic
contain C and H atoms (lots of C – H and C – C bonds).
a.
neutral fats (triglycerides = fats)
3 fatty acids and one glycerol ------ triglycerides
i.
saturated fats: no double bonds in FA (Fatty acid) chain
(solid at room temperature) = coconut oil, animal fats
ii.
monosaturated fats: one double bond in FA chain (liquid; olive
oil)
iii.
polyunsaturated fats: more than one double bond
(more solid at room temp = more of these in canola or
corn oil)
i.
The naturally found kinds are great! See the
table below for oils with polyunsaturated fats.
iii.
a special case = trans fats. These aren’t found
in high amounts in nature; produced artificially
when margarine or shortening is made. Crisco
and margarine producers changed the
manufacturing process to eliminate these bad
fats. Very BAD! They lower HDL, raise LDL
and triglycerides.
FYI:
Oil Types
% saturated fat in different oils
Canola oil
Olive oil
Margarine
Chicken fat
Palm oil
Beef fat
Butter fat
Coconut oil
b.
c.
d.
3.
6
14
17
31
51
52
66
77 ouch! Try not to eat this!
phospholipids
i.
nitrogen/phosphate group on one of the FA of a
triglyceride
ii.
polar head and non-polar tail
steroids
i.
ots of C – C and C – H bonds! Very hydro__________!
ii.
Examples include: aldosterone, estrogen, testosterone,
progesterone
eicosanoids (prostaglandins). We won’t discuss these.
Proteins Physio intro-11B
17% of the body weight
20 different amino acids are the building blocks of protein
Figure 2.16, page 49, Physio Intro-9
R
I
H2N – C - COOH
amino
I
carboxyl group
group
H
Amino acid- general structure
R = 20 different groups
are posssible
Protein structure – three or four levels of complexity
1.
Primary structure: sequence of amino acids linked by peptide bonds.
The chemical roperties of a protein and its folding depend on the chemical
groups that comprise the side chains (R groups).
H
|
+H3N— C—COO|
R
R group varies for each amino acid
The 20 amino acids are often grouped based on similar chemical properties.
Hydrophilic (water-soluble)
Basic
Lysine
Arginine
Histidine
Acidic
Aspartate
Glutamate
other polar amino acids
Serine
Threonine
Asparagine
Glutamine
Hydrophobic
Alanine
Valine
Isoleucine
Methionine
Phenylalanine
Tryptophan
Some amino acids can be easily remembered based on their unique properties.
Amino acid(s)
--containing sulfur:
methionine, cystine
--with H as the R group: glycine
--which is an imino acid: proline
--with aromatic side chains: phenylalanine, tyrosine,
tryptophan
--with –OH (alcohol) groups in side chain: serine, threonine
How is a peptide bond formed between 2 amino acids?
Figure 2.17, page 49
Carbonyl carbon from carboxylic acid group of one amino acid is linked to the amino
nitrogen of the next with removal of water. Dehydration synthesis forms a peptide bond
by removing H2O to link two amino acids together! Hydrolysis breaks the peptide bond.
2.
Secondary structure: localized arrangement of parts of the polypeptide chain into folds
called alpha helix or a beta-pleated sheet. These structures are due to a regular pattern
of hydrogen bonds.
Figure 2.18, page 51
Alpha helix: hydrogen bonding among residues in a protein spaced 4 apart.
Shown as coil or cylinder in schematic diagrams of proteins.
Beta sheet: hydrogen bonding between two chains (at least 5-8 residues at a
stretch) in a protein. Causes the protein to form a corrogated sheet. Shown as
ribbons in schematic diagrams.
3.
Tertiary structure: Three dimensional folding of proteins mediated by many different
types of bonds and interactions. (It is a further folding of the secondary structure).
4.
Quaternary structure: Three dimensional structure of a multi-subunit protein. This occurs
when different protein chains associate with each other. Hemoglobin and myoglobin as
examples.
Fibrous versus Globular Proteins
Table 2.3 , page 52
More functional versus more structural
Fibrous = structural with repeating subunits (collagen, elastin, reticular
fibers)
Globular = more variable structure (enzyme, receptors,
transport proteins, antibodies, etc.)
How can you alter the function of a protein? Denature it =denaturation
1.
2.
3.
Heat it (fever)
Change the pH around it (acidosis, alkalosis)
Increase the ions around it (may be able to “salt it out” of solution)
Denaturation by high heat (boiling) is almost always irreversible.
Figure 2.19, page 53
Some of the Possible Roles of Proteins in the Body
•
Hormone
•
Cell surface or intracellular receptor
•
Enzyme
•
Structural component
•
Transporter (ion channel, carrier protein)
•
Antibodies (defense)
•
Movement (muscle proteins)
Enzymes
A protein + a cofactor (“helper” molecules or ions needed for activity; are ions, vitamins)
Characteristics
1.
show specificity (interact by lock and key binding to their substrate)
2.
not used up when they act; are reused over and over again
3.
not permanently modified
4.
composed of amino acids (they are proteins)
5.
decrease the activation energy of a chemical reaction so it goes faster
6.
are globular proteins
How do they work?
Figure 2.20, page 54, and Figure 2.21, page 55
Enzymes versus Cell Surface Receptors
There are two types of proteins that we talk about that use lock-and-key binding; namely enzymes and
cell receptors. The receptors may be in the cell membrane or inside the cell. There are specifid terms
used for each of these systems.
Property or Characteristic
Enzyme
Cell Receptor
What binds?
Substrate
Ligand
Binding site name?
Active site
Receptor binding site
Affinity
(goodness of fit)
yes
yes
Specificity
(lock and key)
yes
yes
There is a lot of debate about the naming of different-sized proteins
Protein/Polypeptide = >50 amino acids long
Peptide = < 50 amino acids long
4.
Nucleic Acids Physio Intro-11, 12
contain C, H, N, O, P atoms
i.
monomers = nucleotides (building blocks)
ATCG nucleotides in DNA (stores genetic info)
Figure 2.22, page 56,
AUCG nucleotides in RNA (used to make protein)
ii.
macromolecules (DNA, RNA)
Complementary base pairing links nucleotides in DNA
iii.
ATP, GTP (high energy molecules) Figure 2.23, page 57
Potential energy: energy stored in chemical bonds
Red squiggle in picture – high energy bond
“energy cash for cell”
not “banked” for long – only a few seconds
What is ATP used for? Figure 2.24, page 59
1.
transport work
2.
metabolism (chemical work)
3.
cell signaling
4.
cell division
5.
muscle contraction (3,4 & 5 are mechanical work)
Nucleotide structure
Base-sugar-phosphate
If no –OH on “R” = deoxyribose
If an –OH is present = ribose
Dehydration synthesis and hydrolysis
Happens to be used to build up and break down the basic macromolecules of the body
(proteins, nucleic acids, polysaccharides, lipids)
Cell theory:
1.
2.
3.
4.
5.
6.
the cell is the smallest living unit
the function of a cell depends upon its structure
cells are the living building blocks of all living organisms
an organism’s structure and function depend on the properties and structure of its cells
and the fact that they work independently and cooperatively
all cells arise from pre-existing cells
the cells of all organisms are similar in structure and function
Cell structure and function Figure 3.1, pg 65
Not all of the DNA found inside a cell nucleus is used (expressed). As cells mature (differentiate) they
turn off many genes and only use some to make some proteins. In doing this they become “specialists” =
become fully differentiated (see Figure 17.11, page 661 which shows the differentiation of a stem cell in
the bone marrow to become a specific type of WBC).
This is why there are over 200 different cell types in the body.
The composite or average cell, shown in your text book, doesn’t exist!
(>200 different cell types in the body) Figure 3.2, pg 66
What are the functions of the cell membrane?
1.
acts as a physical barrier
2.
regulates a cell’s interaction with the environment (selective permeability)
3.
senses the environment (contains receptors)
4.
provides structural support for the cell
Fluid Mosaic Model of the Cell Membrane Figure 3.3, pg 67, Physio intro 13
3 major components
1.
phospholipids
i.
bilayer has a specific orientation in water
ii.
some molecules with lipids attached to form glycolipids
2.
proteins
i.
there are integral (membrane spanning) and peripheral proteins
ii.
some membrane proteins have lipids attached, forming glycoproteins –
used for cell anchoring and recognition
3.
cholesterol
i.
stabilize the membrane
ii.
makes it more fluid
fluid = proteins and lipids float in the membrane
mosaic = proteins stud the surface of the cell membrane; look like mosaic
What roles can cell membrane proteins have? Figure 3.4, pg 68
1.
transport (ion channels/carriers/pumps)
2.
surface receptors (used for signal transduction)
3.
enzymes
4.
used for cell-to-cell recognition
5.
anchors
6.
cell-to-cell attachment
Ligand = something that binds to a cell receptor binding site
Effect of Ligand binding on Cell Function Physio Intro-12
The specific binding of a ligand to a cell surface receptor can cause one of a number of cellular
changes, such as:
1.
secretion
2.
uptake of a substance
3.
cell division
4.
production of a specific protein
5.
opening of an ion channel
6.
change of the charge of the cell membrane
and many other specific effects!
G-protein linked systems are used in cases when a ligand binds to a cell surface receptor
(Figure 3.16, page 84). We will discuss this in detail later.
Types of Membrane Junctions
1.
tight junctions
molecules can pass between cells; means that the cells must regulate what gets
in and out
located in the digestive tract, blood-brain barrier, and kidney
2.
desmosomes
don’t allow two cells to separate; “glues” them together
located in skin, heart muscle
3.
gap junction
allows cells to share ions; more than 20 different types of gap junctions found to
date
located in many cells including cardiac cells and smooth muscle
Cell membrane permeability
What happens if a cell is impermeable? ______________________________________
What happens if a cell is permeable? _______________________________________
What happens if a cell is selectively permeable? ______________________________
Active and Passive Processes Table (see Table 3.1, page 75 and Table 3.2, page 80)
ECF and ICF