HANDOUT IN BIOCHEMISTRY

PROTEINS AND RELATED FUNCTIONS

AMINO ACIDS

- Except for proline, amino acids contains both amine (-NH 2) and carboxyl (-COOH) functional
groups
- General formula: H2NCHRCOOH, where R is an organic substituent
- the amino and carboxylate groups are attached to the same tetrahedral carbon atom, the α-carbon
- amino acids are linked by peptide bonds to form protein (refer to Fig. 3.1, Boyer)
- each amino acid (except glycine) can occur in two ismeric forms: L- and D-, because it can form
two different stereoisomers around the central carbon atom (refer to Fig. 3.2, Boyer)
- Only L-amino acids are found in proteins in all organisms
- Some D-amino acids are found in bacterial cell walls

- ZWITTERION – an amino acid can form a positive/negative ion because an acid and base are
present. (refer to Fig. 3.3, Boyer)

Classification of Amino Acids (refer to Fig. 3.5, Boyer)

1. Amino acids with aliphatic R-groups

2. Non-aromatic with hydroxyl R-groups
3. Amino acids with sulfur-containing R-groups
4. Acidic amino acids and their amides
5. Basic amino acids
6. Amino acids with aromatic rings
7. Imino acid - Proline

PROTEINS

Every function in the living cell depends on proteins: (refer to Table 3.4, Boyer)

1. Motion and locomotion of cells and organisms depends on contractile proteins (e.g., muscles)
2. Catalysis of all biochemical reactions is done by enzymes
3. Structure and extracellular matrix of cells (e.g., collagens)
4. Transport of materials in body fluids
5. Receptors for hormones and other signaling molecules
6. Essential nutrients for heterotrophs*
7. Antibodies of immune system – immunoglobulins

Residue – term used to refer to the amino acid once incorporated into a polypeptide.

Polypeptide – contains 10-100 residues

Protein – contains more than 100 residues

Classification of Proteins
 1. Number of polypeptides used
1.1 Monomeric – only a single polypeptide chain is present
1.2 Oligomeric – two or more polypeptide chains are present

2. According to gross structure (refer to Table 3.6, Boyer)

2.1 Fibrous Proteins – elongated, filamentous, insoluble (e.g., keratin of human hair)
2.2 Globular Proteins – folded and coiled, soluble (e.g., hormones, enzymes)

3. According to composition
3.1 Simple Proteins – absence of non-protein components
3.2 Complex or Conjugated Proteins - incorporate other types of compounds (prosthetic group)
that
perform a specific function.
3.2.1 Glycoproteins – linked to carbohydrates (e.g., immunoglobulins)
3.2.2 Nucleoproteins – linked to nucleic acids (e.g., chromosomes)
3.2.3 Metalloproteins – linked to metal ions (e.g., cytochrome C)
3.2.4 Lipoproteins – linked to lipids of various types (e.g., eggyolk)
3.2.5 Chromoproteins – with colored prosthetic groups or various pigments (e.g.,
hemoglobin)
3.2.6 Phosphoproteins – linked to phosphorus other than nucleic acids and lecithin (e.g.,
casein of milk)

Denaturation – protein unfolding; the unraveling of a protein’s structure; the disorganized protein will
no longer act as intended. When this occurs, protein strands will clump together – coagulate.
Temperature, pH, chemicals, and radiation outside the normal range can both cause denaturation.

Hydrolysis – this will result in protein being reduced to simpler peptides and amino acids. Amount of
hydrolysis depends on pH, time and temperature.

Effect of pH on proteins:
- changing pH will alter charge on protein; this alters their solubility and may change their shape.

Methods of Determining Protein Structure

1. Absorbance Spectroscopy
2. Fluorescence

Levels of Protein Structure (refer to Fig. 3.12, Boyer)

1. Primary Structure – refers to the linear number and order of the amino acids present;
convention for the designation of the order of amino acids is that the N-terminal end (bearing the
residue with free α-amino group) is to the left, and the C-terminal end (residue containing free α-
carboxyl group) is to the right. (refer to Fig. 3.10, Boyer)

 Determination of Primary Structure (refer to Fig. 3.15, Boyer)

- Edman method of protein sequencing

- Sequencing DNA
- Importance of protein sequence data
 2. Secondary Structure – conformational forms of proteins; proteins fold into two broad classes of
structure: globular proteins or fibrous proteins. It is the double-bond character of the peptide bond
that defines the conformation a polypeptide chain may assume.

Alpha (α)-Helix – common secondary structure encountered in proteins of the globular class;
formation of the helix is spontaneous and is stabilized by H-bonding between amide nitrogens and
carbonyl carbons of peptide bonds spaced four residues apart.
- orientation of H-bonding produces a helical coiling of the linear peptide backbone (refer to Fig.
4.5, Boyer)

Beta (β)- Sheets – composed of 2 or more different regions of stretches of at least 5-10 amino acids;
H-bonding residues are present in adjacently opposed stretches of the polypeptide backbone; said to
be pleated (refer to Figs. 4.6-4.7, Boyer)

- Beta-sheets are either parallel or antiparallel:

1. Parallel sheets - adjacent peptide chains proceed in the same direction (the direction of N-
terminal to C-terminal ends is the same)
2. Antiparallel sheets - adjacent chains are aligned in opposite directions

3. Tertiary Structure – refers to the complete three-dimensional structure of the polypeptide units
of a given protein; secondary structures themselves fold into the three-dimensional form of the
protein.; describes the relationship of different domains to one another within a protein. The
interactions of different domains is governed by several forces:
- H-bonding
- Hydrophobic interactions
- Electrostatic interactions
- Van der Waals forces

4. Quaternary Structure – structure formed by monomer-monomer interaction in an oligomeric

protein. Oligomeric proteins can be composed of multiple identical polypeptide chains or
multiple distinct polypeptide chains.

Forces Controlling Protein Structure (review and refer to Fig. 4.3, Boyer)

1. Hydrogen bonding
2. Hydrophobic forces
3. Electrostatic forces
4. van der Waals forces

HEMOGLOBIN

 symbol used is Hb
 the iron-containing oxygen transport metalloprotein in the red blood cells of the blood in
vertebrates and other animals.
 each subunit of Hb is a globular protein with an embedded heme group; each heme group
contains an iron atom, and this is responsible for the binding of oxygen (refer to Fig. 4.16,
Boyer)
 in humans, each heme group is able to bind one oxygen molecule, and thus, one Hb molecule
can bind four oxygen molecules
  In mammals, the protein makes up about 97% of the red blood cell’s content, and around 35%
of the total content (including water).
 Functions of hemoglobin: 1) transports oxygen from the lungs or gills to the rest of the body,
such as to the muscles, where it releases its load of oxygen; 2) other gas-transport and effect-
modulation duties
 The heme portion is synthesized in a series of steps which occur in the mitochondria and the
cytosol of the immature red blood cell; the globin protein portions of the molecule are
synthesized by ribosomes in the cytosol.
 A heme group consists of an iron (Fe) atom held in a heterocyclic ring known as porphyrin. The
iron atom, which is the site of oxygen binding, bonds with the four nitrogens in the center of the
ring, which all lie in one plane. (refer to Figs. 4.17-4.18, Boyer)
 The iron atom must exist in the 2+ oxidation state in order to bind oxygen.
 The four polypeptide chains of Hb A are bound to each other by salt bridges, hydrogen bonds,
and hydrophobic interactions.
 mutations in the genes for the Hb protein in humans result in a group of hereditary diseases
termed the hemoglobinopathies, the best known of which is sickle-cell disease
 * Sickle cell anemia – results in one misplaced amino acid. In this condition, it still transports
oxygen but results in deformed blood cells – elongated, sickle-shaped, difficult to pass through
capillaries; causes organ damage and reduced circulation. (refer to Fig. 4.24, Boyer)
 Thalassemias – set of diseases that involves underproduction of normal and sometimes abnormal
Hbs, through problems and mutations in globin gene regulation; these diseases also often produce
anemia.
 Not all globin-gene mutations result in illness; these mutations are recognized as hemoglobin
variants rather than diseases.
 In adult humans, the most common hemoglobin type is Hb A, which contains 4 subunit proteins
consisting of two alpha and two beta subunits non-covalently bound, each made of 141 and 146
amino acid residues, respectively.
 Oxyhemoglobin is formed during respiration when oxygen binds to the heme component of the
protein Hb in red blood cells. This process occurs in the pulmonary capillaries adjacent to the
alveoli of the lungs. The oxygen then travels through the blood stream to be dropped off at cells
where it is utilized in aerobic glycolysis and in the production of ATP by the process of oxidative
phosphorylation (refer to Fig. 4.22, Boyer)
 Deoxyhemoglobin is the form of Hb without the bound oxygen. (refer to Fig. 4.22, Boyer)
 The absorption spectra of oxyhemoglobin and deoxyhemoglobin differ. This difference is used
for measurement of the amount of oxygen in patient’s blood by an instrument called pulse
oximeter.
 Anemia has many different causes, although iron deficiency and its resultant iron deficiency
anemia are the most common causes; as absence of iron decreases heme synthesis, red blood cells
in iron deficiency anemia are hypochromic (lacking the red Hb pigment) and microcytic
(smaller than normal)
 Hemoglobin levels are among the most commonly performed blood tests, usually as part of a full
blood count or complete blood count.
 The normal functions of hemoglobin are affected by atmospheric pollutants. One of these
pollutants is carbon monoxide. It reduces the ability of the bloodstream to carry oxygen to the
tissues.
 In hemolysis, the accelerated breakdown of red blood cells, associated jaundice is caused by the
hemoglobin metabolite bilirubin, and the circulating hemoglobin can cause renal failure.
 Porphyria is a genetic disorder that is characterized by errors in metabolic pathways of heme
synthesis.

MYOGLOBIN
  Myoglobin is an unusual protein as it is made up almost exclusively of α-helices joined by short
loops. Most proteins have both α-helices and β-sheets. (refer to Fig. 4.1, Boyer)
 Myoglobin as an example of a water-soluble globular protein. The tertiary (3-D) structure consists
of
an 8 α-helices which fold to make a compact globular protein. The folding occurs in such a
manner
that almost all of the hydrophillic (polar) groups are on the outside of the protein, facing the
aqueous
environment. The hydrophobic groups are almost all inside the protein and the hydrophobic effect
plays a large role in maintaining the stability of the folded protein.
 The helices are amphipathic with the side facing the interior having amino acids with
hydrophobic
side-chains and the side facing to outside having polar side-chains.

Heme Prosthetic Group

 Myoglobin binds oxygen (O2) in muscle tissue. The oxygen binds to an iron atom (Fe 2+) which is
part
of the heme group associated with the myoglobin protein.
 Heme is an example of a prosthetic group, a non-protein group associated with a protein. The
heme group sits in a hydrophobic pocket of myoglobin. The only polar residues in this pocket are
two histidines, one on either side of the heme.
 In myoglobin the prosthetic group (heme) is bound to the protein by non-covalent bonds.
 Heme is made up of four heterocyclic pyrole rings joined at their corners by methylene bridges.
The four nitrogen atoms bind the iron atom. Only the Fe2+ (ferrous states) can bind O2. Iron
is capable of forming two additional bonds on either side of the plane of the heme and these
additional bonds are important in the association of heme with myoglobin and for the binding
of oxygen.

 If O2 binds to a free ferrous hem group in solution, the Fe 2+ is immediately oxidized to Fe3+ and
the
O2 is reduced. The interaction of the heme with the myoglobin protein prevents the oxidation
occurring and allows the heme prosthetic group in myoglobin to carry oxygen.

Oxygen Delivery and Storage

 Hemoglobin provides a means of getting oxygen to metabolizing tissues, but cells also need a
means
to bind and store oxygen released from the hemoglobin as blood passes through the capillaries.
This
function is carried out by the intracellular protein myoglobin, a structural relative of hemoglobin.
 The hemoglobin in the red blood cells and myoglobin inside tissues such as muscle cells have to
act in tandem for effective oxygen transport. For hemoglobin the task is to become completely
loaded with oxygen as the blood traverses through the capillaries of the lungs. It must then be
able to efficiently off-load oxygen when the blood flows past the low oxygen environment of
active tissues, such as heart muscles.
 By contrast to hemoglobin, to perform its job, myoglobin (Mb) must effectively bind any oxygen
released from hemoglobin (Hb). Myoglobin therefore needs to have a higher oxygen affinity than
hemoglobin.
COLLAGEN

 the main protein of connective tissues in animals and the most abundant protein in mammals
 they are long, fibrous structural proteins (refer to Figs. 4.11-4.12, Boyer)
 Make up about 25% of the total protein content
 It has great tensile strength
 collagen fibers are a major component of the extracellular matrix that supports most tissues and
gives cells structure from the outside
 the main component of fascia, cartilage, ligaments, tendons, bone, and teeth
 along with soft keratin, it is responsible for skin strength and elasticity, and its degradation leads
to wrinkles that accompany aging
 it strengthens blood vessels and plays a role in tissue development
 it is present in the cornea and lens of the eye in crystalline form
 Vit. C deficiency causes scurvy, a serious and painful disease in which defective collagen
prevents the formation of strong connective tissue; gums deteriorate and bleed, with loss of teeth;
skin discolors, and wounds do not heal
 Autoimmune disease, a malfunction of the immune system, results in an immune response in
which healthy collagen fibers are systematically destroyed with inflammation of the surrounding
tissues; the resulting disease processes are called Lupus erythematosus, and rheumatoid
arthritis, or collagen tissue disorders

 Composition and structure:

 The tropocollagen or “collagen molecule” is made up of three polypeptide strands, each
of which is a left-handed helix..
 There is covalent crosslinking within the triple helices, and a variable amount of
covalent crosslinking between tropocollagen helices, to form the different types of
collagen found in different mature tissues – similar to the situation found with the α-
keratins in hair.
 Collagen gives bone its elasticity and contributes to fracture resistance.
 Collagen occurs in many places throughout the body. There are 28 types of collagen described in
literature.
 Collagen diseases commonly arise from genetic defects that affect the biosynthesis, assembly,
posttranslational modification, secretion, or other processes in the normal production of collagen.

Amino Acids

 A distinctive feature of collagen is the regular arrangement of amino acids in each of the three
chains of these collagen subunits. The sequence often follows the pattern Gly-X-Pro or Gly-X-
Hyp, where X may be any various other amino acid residues.
 Glycine (Gly) is found at almost every third residue.
 Proline (Pro) makes up about 9% of collagen
 Hydroxyproline (Hyp) is derived from praline; hydroxylation of proline amino acid occurs inside
the lumen. This process is dependent on Ascorbic acid (Vitamin C) as a cofactor.

Industrial uses:

 produces gelatin, which is used in many food, pharmaceutical, cosmetic, and photography
industries
 source of collagen adhesives (glues)
  animal glues are thermoplastic (softening again upon reheating), used in making musical
instruments, e.g., fine violins and guitars

Medical uses:

 used in cosmetic surgery, as a healing aid for burn patients for reconstruction of bone and a wide
variety of dental, orthopedic and surgical purposes
 most medical collagen is derived from young beef cattle from certified BSE (Bovine spongiform
encephalopathy) free animals; porcine (pig) tissue is also widely used for producing collagen
sheet for a variety of surgical purposes
 widely employed in the construction of artificial skin substitutes used in the management of
severe burns

ELASTIN

 A protein which possesses unique elasticity and strength

 Elastin fibers enable tissues such as skin, arteries, and ligaments to stretch and rebound. The
presence of this protein in the arteries enables the artery wall to alternately stretch and rebound as
blood pulses through.
 It is also present in the walls of alveoli allowing the air sacs of the lungs to expand with
inhalation and relax with exhalation.
 Elastin is chemically inert, resistant to mild hydrolysis by acid or alkali.
 Tropoelastin – precursor of elastin; it matures to form elastin
 The structure of elastin has frequent occurrence of a val-pro sequence. This sequence can give
rise to a unique coiling which can produce the observed behavior of elastin on stretching and
recoil.

KERATIN

 Keratin – the protein of wool, claws of reptiles, feathers, beaks of birds, horns, skin, hair, and
nails of mammals, scales of fish, etc., are insoluble.
 Keratins are made of two kinds of material, one forming the fibrous structure and the other
forming the cement that crosslinked it three-dimensionally.
 Hair – consists of fine, densely-packed filaments or microfibrils set in an amorphous matrix that
apparently crosslink them together. (refer to Fig. 4.25, Boyer)
 It is evident that keratins owe their insolubility to the fact that they are composed of molecular
chains crosslinked three dimensionally by disulfide bonds.
 Cleavage of the disulfide bonds by a reducing agent like mercaptoethanol and an oxidizing
agent like performic acid rendered wool and feather keratins soluble.

CYTOCHROME C or cyt c

 is a small heme protein found loosely associated with the inner membrane of the mitochondrion
 it is a soluble protein and is an essential component of the electron transfer chain
 capable of undergoing oxidation and reduction, but does not bind oxygen
 a highly conserved protein across the spectrum of species, found in plants, animals, and many
unicellular organisms
 its primary structure consists of a chain of 100 amino acids
  it is an intermediate in apoptosis, a controlled form of cell death used to kill cells in the process
of development or in response to infection or DNA damage
 It is useful in studies of evolutionary divergence.
 Both chickens and turkeys have the identical molecule within their mitochondria, whereas ducks
possess molecules differing by one amino acid.
 Similarly, humans and chimpanzees have the identical molecule, while rhesus monkeys possess
cytochromes differing by one amino acid.
 Functions: can catalyze several reactions such as 1) hydroxylation, 2) aromatic oxidation, and 3)
peroxidase activity by oxidation of various electron donors, 4) an intermediate of apoptosis
(programmed cell death, used to kill cells in the process of development or in response to
infection or DNA damage).
 Cytochrome c is released by the mitochondria in response to pro-apoptotic stimuli.

SERUM ALBUMIN

 the most abundant plasma protein in humans and other mammals

 essential for maintaining the osmotic pressure needed for proper distribution of body fluids
between intravascular compartments and body tissues
 acts as a plasma carrier by non-specifically binding several hydrophobic steroid hormones and as
a transport protein for hemin and fatty acids
 albumin is negatively charged, this prevents the filtration of albumin in the urine
 in nephrotic syndrome, this property is lost, and there is more albumin loss in the urine
 Nephrotic syndrome patients are given albumin to replace the lost albumin.
 human serum albumin is the most abundant protein in human blood plasma; it is produced in
the liver; albumin comprises about half of the blood serum protein; it is soluble and monomeric
 the gene for albumin is located on chromosome 4 and mutations in this gene can result in various
anomalous proteins
 maintains oncotic pressure, transport thyroid hormones, “free” fatty acids to the liver, drugs, and
unconjugated bilirubin, and buffers pH
 Hypoalbuminemia (low blood albumin levels) can be caused by: 1) cirrhosis of the liver, 2)
decreased production (as in starvation), 3) excess excretion by the kidneys (as in nephrotic
syndrome), 4) excess loss in bowel, and others.
 In the healthy kidney, albumin’s size and negative electric charge exclude it from excretion in the
glomerulus. In the case of nephrotic syndrome, the protein can cross the glomerulus. The lost
albumin can be detected by a simple urine test.
 Depending on the amount of albumin lost, a patient may have normal renal function,
microalbuminuria, or albuminuria.

ANTIBODIES

 Antibodies, also called immunoglobulins or Igs, constitute the gamma globulin part of the
blood
proteins. They are soluble proteins secreted by the plasma offspring (clones) of primed B
cells.
 they are Y-shaped proteins that are found in blood or other bodily fluids, and are used by the
immune system to identify and neutralize foreign objects like bacteria and viruses
 They are made up of a few basic structural units called chains
 each antibody has two large heavy chains and two small light chains
  although the general structure of all antibodies is very similar, a small region at the tip of the
protein is extremely variable; each of these different variants can bind to different targets, which
are known as antigens; the unique part of the antigen recognized by an antibody is called an
epitope, which fits precisely with its specific antibody, similar to a key fitting to a lock. This
highly specific interaction allows antibodies to identify and bind only their antigen in the midst of
all organism’s own molecules.
 Antibodies occur in two forms: a soluble form secreted into the blood and tissue fluids, and a
membrane-bound form attached to the surface of a B cell that is called the B cell receptor
(BCR). The BCR allows a B cell to detect when a specific antigen is present in the body and
triggers B cell activation.
 Antibodies are an essential component of the adaptive immune system that learns, adapts and
remembers responses to invading pathogens. Production of antibodies is the main function of the
humoral immune system.
 Antibodies can neutralize antigens directly by binding to a part required by a pathogen to cause
an infection.
 Activated B cells differentiate into either: 1) antibody generating factories called plasma cells
that secrete soluble antibody, or into 2) memory cells that survive in the body for years
afterwards, allowing an organism to remember an antigen and respond faster upon future
exposures.

Structure:

 they are heavy globular plasma proteins that are also known as immunoglobulins
 have sugar chains added to some of their amino acid residues, thus, antibodies are glycoproteins
 the basic functional unit of each antibody is an immunoglobulin (Ig) monomer
 Antibodies exist freely in the bloodstream, and are said to be part of the humoral immune
system

* The antibodies inactivate antigens by:

(a) complement fixation - proteins attach to antigen surface and cause holes to form, i.e., cell lysis
(b) neutralization - binding to specific sites to prevent attachment—this is the same as taking their
parking space
(c) agglutination - clumping
(d) precipitation - forcing insolubility and settling out of solution, and other more arcane methods.

 Constituents of gamma globulin are: IgG-76%, IgA-15%, IgM-8%, IgD-1%, and IgE-0.002%
(responsible for autoimmune responses, such as allergies and diseases like arthritis, multiple
sclerosis,
and systemic lupus erythematosus).

* IgG is the only antibody that can cross the placental barrier to the fetus and it is responsible for the 3
to 6 month immune protection of newborns that is conferred by the mother.

* IgM is the dominant antibody produced in primary immune responses, while IgG dominates in
secondary immune responses. IgM is physically much larger than the other immunoglobulins.

Neutralization:
  antibodies that recognize viruses block the ability of the pathogen to dock to its preferred receptor
by binding them directly; bound virus is unable to infect a host cell; e.g., antivenoms neutralize
toxins by binding to them
 Viruses and intracellular bacteria must enter a cell to benign replication; they gain entry into
the cell by binding to specific molecules on the cell surface.
 some viruses are able to evade the immune system when antibody neutralization is inadequate;
e.g., HIV virus are not completely covered by neutralizing antibody, the antibodies may enhance
viral infectivity instead of inhibiting it; HIV prefers to infect cells that bind to antibodies
 antibodies cannot attack pathogens within cells, and certain viruses “hide” inside cells for long
periods of time to avoid neutralization
 during chronic diseases such as herpes, an outbreak is quickly suppressed by the immune system,
but some cells retain virus that will reactivate later and cause a resurgence of symptoms; the
infection is never truly eradicated

Disease diagnosis:

 Detection of particular antibodies is a very common form of medical diagnostics, and

applications such as serology depend on these methods.
 Ex. A titer of antibodies directed against Epstein-Barr virus or Lyme disease is estimated from
the blood. If those antibodies are not present, either the person is not infected, or the infection
occurred a very long time ago, and the B cells generating these specific antibodies have naturally
decayed.
 Autoimmune disorders can often be traced to antibodies that bind the body’s own epitopes;
many can be detected through blood tests.

HORMONES

Structure and Function of Hormones

 The integration of body functions in humans and other higher organisms is carried out by the
nervous system, the immune system, and the endocrine system.
 The endocrine system is composed of a number of tissues that secrete their products, endocrine
hormones, into the circulatory system; disseminated throughout the body, regulating the function
of
distant tissues and maintaining homeostasis.
 Exocrine tissues secrete their products into ducts and then to the outside of the body or to the
intestinal tract.
 Endocrine hormones are considered to be derived from amino acids, peptides, or sterols and to
act
at sites distant from their tissue of origin. However, it is found that some secreted substances act
at a
distance (classical endocrines), close to the cells that secrete them (paracrines), or directly on
the cell
that secreted them (autocrines).
 Hormones are normally present in the plasma and interstitial tissue at concentrations in the
range
of 10-7M to 10-10M.
  Once a hormone is secreted by an endocrine tissue, it generally binds to a specific plasma
protein
carrier, with the complex being disseminated to distant tissues.
 Plasma carrier proteins exist for all classes of endocrine hormones.
 Carrier proteins for peptide hormones prevent hormone destruction by plasma proteases.
 Carriers for steroid and thyroid hormones allow these very hydrophobic substances to be present
in
the plasma at concentrations several hundred-fold greater than their solubility in water would
permit.  Carriers for small, hydrophilic amino acid-derived hormones prevent their filtration
through the renal
glomerulus, greatly prolonging their circulating half-life.
 Tissues capable of responding to endocrines have 2 properties in common: they posses a receptor
having very high affinity for hormone, and the receptor is coupled to a process that regulates
metabolism of the target cells.
 Receptors for most amino acid--derived hormones and all peptide hormones are located on the
plasma membrane. Activation of these receptors by hormones (the first messenger) leads to the
intracellular production of a second messenger, such as cAMP, which is responsible for initiating
the
intracellular biological response.
 all multicellular organisms produce hormones
 Function of hormones: to serve as a signal to the target cells; the action of hormones is
determined by the pattern of secretion and the signal transduction of the receiving tissue.
 Endocrine hormone molecules are secreted (released) directly into the bloodstream, while
Exocrine hormones are secreted directly into a duct, and from the duct they either flow into the
bloodstream or they flow from cell to cell by diffusion in a process known as paracrine
signaling.
 Hormone effects vary widely, but can include: stimulation or inhibition of growth, induction or
suppression of apoptosis, activation or inhibition of the immune system, regulating metabolism,
preparation for a new activity (e.g., fighting, mating), preparation for a new phase of life (e.g.,
puberty, menopause), and controlling the reproductive cycle.
Growth Hormone

 Human placental lactogen (hPL), growth hormone (GH), and prolactin (PRL) comprise the
growth hormone family. All have about 200 amino acids, 2 disulfide bonds, and no glycosylation.
Although each has special receptors and unique characteristics to their activity, they all possess
growth-promoting and lactogenic activity.
 There are a number of genetic deficiencies associated with GH. GH-deficient dwarfs lack the
ability
to synthesize or secrete GH, and these short-statured individuals respond well to GH therapy.
 Laron dwarfs have normal or excess plasma GH, but lack liver GH receptors and have low
levels of
circulating Insulin-like growth factor (IGF-1). The defect in these individuals is clearly related to
an
inability to respond to GH by the production of IGF-1.
 The production of excessive amounts of GH before epiphyseal closure of the long bones leads to
gigantism, and when GH becomes excessive after epiphyseal closure, acral bone growth leads to
the
characteristic features of acromegaly.
PEPTIDE ANTIBIOTICS

 Antibiotics are chemical substances produced by microorganisms that can inhibit the growth of
other microorganisms or even destroy them.
 Ex. Gramicidin S (an antibiotic for topical use and found to be very effective against gram (+)
bacterial infection). It contains ornithine which is not normally found in proteins, it also has D-
phenylalanine. It is a cyclic decapeptide which has hydrophobic as well as hydrophilic groups
on the side chain.
 Ex. Polymyxin B1 is another peptide antibiotic containing 10 amino acid residues, one of which
is phenylalanine with the D-configuration. It contains a diaminobutyric acid and a
cycloheptapeptide ring with an N-alkylated tripeptide side chain. Polymyxin has potent
bactericidal activity against gram (-) bacilli.
 The overall molecular conformation and the general chemical nature (hydrophobic and
hydrophilic) of the side chains of the constituent amino acids are the chief features which give
rise to antibacterial activity.

PEPTIDE HORMONES

 The principal hormones of the posterior pituitary are the nonapeptides oxytocin and vasopressin.
These substances are synthesized as prohormones in neural cell bodies of the hypothalamus and
mature as they pass down axons in association with carrier proteins termed neurophysins. The
axons
terminate in the posterior pituitary, and the hormones are secreted directly into the systemic
circulation.
 Vasopressin is also known as antidiuretic hormone (ADH), because it is the main regulator of
body fluid osmolarity. The secretion of vasopressin is regulated in the hypothalamus by
osmoreceptors, which sense water concentration and stimulate increased vasopressin secretion
when
plasma osmolarity increases. (refer to Fig. 3.11, Boyer)
 The secreted vasopressin increases the reabsorption rate of water in kidney tubule cells, causing
the
excretion of urine that is concentrated in Na+ and thus yielding a net drop in osmolarity of body
fluids.
 Vasopressin deficiency leads to watery urine and polydipsia, a condition known as diabetes
insipidus.
 The mechanism of action of oxytocin is unknown. Oxytocin secretion in nursing women is
stimulated
by direct neural feedback obtained by stimulation of the nipple during suckling. Its physiological
effects include the contraction of mammary gland myoepithelial cells, which induces the ejection
of
milk from mammary glands, and the stimulation of uterine smooth muscle contraction leading to
childbirth. (refer to Fig. 3.11, Boyer)
 Insulin – another peptide hormone, is produced in the pancreas. It regulates the metabolism of
carbohydrates. Failure of the pancreas to secrete an adequate amount of insulin causes diabetes, a
disease characterized by a disorder in carbohydrate and lipid metabolism.
 Insulin is synthesized in the pancreas as a single chain inactive hormone, known a proinsulin. It is
activated by the action of trypsin which removes fragment 31 to 63.
 The insulin receptor (molecule uniquely capable of recognizing and thus interacting with insulin)
is
membrane localized. The binding activity is destroyed by trypsin indicating that the receptor is a
protein.
 Other metabolic processes associated with the action of insulin are:
1. protein synthesis
2. redirection of glucose and lipid metabolism
3. increase permeability of cell membranes to sugars and amino acids