Running head: AMINO ACIDS & PEPTIDE BONDS: PROTEIN STRUCTURE 1

Amino Acids and Peptide Bonds: Protein Structure

Delia Garcia

GRT-1 Biochemistry

February 16, 2015

Julie Thompson
AMINO ACIDS & PEPTIDE BONDS, PROTEIN STRUCTURE 2

Amino Acids & Peptide Bonds, Protein Structure

The first few amino acids were originally discovered in the early 19th century; the first of

which was discovered in 1806 by French chemists Louis-Nicolas Vauquelin and Pierre Jean

Robiquet who isolated a compound in asparagus that was subsequently named asparagine

(Vauquelin & Robiquet, 1806). The term amino acid refers to several distinctive

macromolecules, 20 of which are considered essential. Essential amino acids are similar in

structure as they share a chemically similar organic structural backbone; yet, they remain

uniquely diverse as each side chain differs in biological configuration and characteristic function.

Molecular proteins are also linear macromolecules which encompass several amino acids

linked together. Proteins are the most diverse group of biologically important substances and are

often considered to be the central compound necessary for life. In fact, the translation from the

Greek root word means first place. (Green, 2012). Whats perhaps more interesting is that of

these 20 essential amino acids, nine do not naturally occur within the body. These amino acids

include histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan,

and valine (Green, 2012). However, these proteins can by synthesized through digestion of

foods high in protein.

Amino Acid Structure

Amino acids are instrumental in manufacturing protein; each amino acid is comprised of

a carboxylic acid group, an amine group, a chiral carbon atom ( carbon), a hydrogen atom, and

the unique side chain or R group. In relation to structure, the R group is what entitles the

individual designation of each amino acid. The elements which make up the amino acid

backbone, such as nitrogen, carbon, hydrogen, and oxygen bond together with the side chain to
AMINO ACIDS & PEPTIDE BONDS, PROTEIN STRUCTURE 3

form each individual amino acid, and these amino acids can then be classified even further; for

instance, some are polar, others are nonpolar (Moulton, 2004).

Hydrophobic molecules have a hatred of water, and therefore are non-polarized.

Hydrophilic molecules have a love and affinity for water, therefore are polarized. Molecules can

also carry a charge, either positive or negative and can be bonded by hydrogen. Various forces

cause these bonds to occur. Hydrogen bonds essentially stick together on the hydrogen side of

the molecule, and are generally weak. Covalent bonds occur in two elements with a similar

electronegativity. Polar covalent bonds occur when an electron is drawn to one side of the atom.

Ionic bonds occur when one atom either donates or accepts and electron to form an ion (a

charged atom).

Leucine

Leucine is one of the 20 essential amino acids which must be ingested in order to be

synthesized by the body, as it is not naturally present. Leucine is one of the three amino acid

with a branched hydrocarbon side chain (Biology Project, Biochemistry, 2003). Leucine is a

hydrophobic amino acid that is utilized by the body within the liver, muscle, and adipose tissue.

Leucine is unique in that of the 20 amino acids, it alone has the ability to inspire muscle protein

synthesis. Similar to isoleucine and valine, the absence of a certain enzyme may subsequently

result in the buildup of leucine in the blood and urine; a disorder known as maple syrup urine

disease (MSUD) (New World Encyclopedia, para. 2, 2014).

Protein Synthesis

Proteins are formed through a process of polymerization in which various essential

amino acids formulate peptide bonds. A peptide bond (amide bond) is a covalent chemical bond

formed between two amino acid molecules; which ultimately produce the appropriate folding
AMINO ACIDS & PEPTIDE BONDS, PROTEIN STRUCTURE 4

confirmation in a polypeptide chain or protein (Khan Academy, 2014). This course of

development begins once the initial amino acid formulates a bond with an additional amino acid.

The ensuing bond of multiple peptide bonds forms the previously designated polypeptide chain;

therefore once one or more polypeptide chains combine, a protein is ultimately formed. The

final protein structure is dependent upon the amino acids that compose it (Moltan, 2004).

Dehydration and Hydrolysis

Peptide bonds are formed through the process of dehydration in which a nucleophilic

addition elimination reaction of the carboxyl group of one amino acid and the amine group of

another amino acid to produce a rigid and planar bond stabilized by resonant stabilization.

However, this progression roots the loss of a water (H0) molecule. Conversely, cleavage occurs

when the bonds between amino acids are broken down through the process of hydrolysis.

Hydrolysis can be achieved through various reactions caused by the addition of water (a solvent),

strong acids, or proteolytic enzymes.

When adding a water molecule to the peptide bond formed through dehydration, the bond

is broken apart and two individual amino acids remain. In the process of Acid Hydrolysis, the

peptide bond is broken apart by a strong acid being heated up to break down each individual

amino acid in a non-specific way. However, in proteolysis a specific breakdown can occur and

amino acids can be fragmented and cut into sections, rather than individual peptides by means of

a protease enzyme. In effect, specificity can come with various protease enzymes which cleave

to specific amino acids. Thus, in contrast to acid hydrolysis cuts can be made in a calculated area

as opposed to an aggregate disunion of each individual peptide.

Protein Aggregation, Conformation, & Denaturation

AMINO ACIDS & PEPTIDE BONDS, PROTEIN STRUCTURE 5

As such, the function of a protein correlates with the specific shape of the protein; and

proteins are considered to be in the active state when conformation is stable. If the three-

dimensional structure of the protein is altered because of a change in the structure of the amino

acids, the protein becomes denatured and does not perform its function as expected(Moltan,

2004). Conformation refers to the proper manner in which a protein folds, there are four levels of

protein structure folding.

This first level is Primary (1) which is a linear sequence of a polypeptide chain. The

secondary structure (2) has a hydrogen bonding interaction at the backbone. The helix and

sheet are examples of 2 structure. The third level is tertiary (3) and has distant interactions at

the R group side chain. The final structure is quaternary (4), and its hydrogen bonding occurs

between separate subunits (multiple polypeptides). A single subunit is known as a tetramer, two

subunits are a dimer, three subunits are a trimer, and four subunits are a multimer.

Protein denaturation occurs when a protein unfolds from its structure or conformational

stability. This in turn, renders the protein to the inactive state. Proteins are protected by the

solvent shell which surrounds the molecule. This shell is generally comprised of electronegative

stability in positively charged atoms. These interactions keep the protein folded properly.

Denaturation can take place in high temperatures, which destroys the secondary, tertiary, and

quaternary structures leaving on the primary structure intact.

Increasing ph. with an acid such as vinegar will disrupt the ionic bonds and destroy the

tertiary and quaternary structures. Chemical reactions which attack the hydrogen bonds lead to

denaturation in all structures leaving only the primary, similar to an increase in temperature.

Enzymes however have the ability to denaturize or break down peptide bonds further, which

result in destruction of the primary structure. Aggregation pf proteins occur when denaturized or
AMINO ACIDS & PEPTIDE BONDS, PROTEIN STRUCTURE 6

mis-folded proteins accumulate together in one of two ways either intra- or extracellular into

what is known as an amyloid. Amyloids are held responsible for many neurodegenerative

symptoms such as dementia and memory loss and are see in Alzheimers disease and Crutchfeild

Jacobs Disease (CJD) or prion disease.

BSE

The crucial event in the development of transmissible spongiform encephalopathies

(TSEs) is the conformational change of a host-encoded membrane protein - the cellular PrPC -

into a disease associated, fibril-forming isoform PrPSc( Kupfer, Hinrichs, & Groschup, para. 1,

2009). Prion disease can be inherited, infectious, or spontaneous, however in any form generates

infectious material. According to BSE info (2015), Prions are a disease-causing form of a

normal protein called cellular prion protein (PrPC) that is located primarily on the surface of

central nervous system cells but also in other tissues of the body in mammals(BSE info, para. 1,

2015). WHen the shape of the protein changes through misfolding, amyloid plaques form, and

these cause the symptoms seen in those suffering from prion disease. According to Kupfer et al,

A conformational transition of the -helix-rich form into the predominantly -sheet

encompassing complement starts an autocatalytic response which results in an accrual of

amyloid fibrils within the central nervous system (CNS) causing neurodegeneration(Kupfer et

al, para. 1, 2009).

The protein responsible for this is denoted Protenacious Infectious Particle (PRPC);

when it becomes misfolded it transforms into PRPSC. The infection of normal cells may occur

when an aberrant prion acts as a template for the refolding of a normal prion into a new aberrant

prion (Simmer, 2006). Chaperone cells are considered helping proteins which attempt to

prevent misfiling and aggregation; however, as this mysterious disease has a unique trifecta of
AMINO ACIDS & PEPTIDE BONDS, PROTEIN STRUCTURE 7

causation, chaperone cells can fail. While the principal role of chaperone cells is ultimately to

preclude or inhibit protein aggregation or misfolding; it appears as if some fungi proteins have

grown an ability to exploit the molecular chaperone mechanisms and to amend the conformation

into an aggregation-prone, infectious form( Jones, & Tuite, 2005). Currently, the exact protein

has yet to be unequivocally named or identified; as such Protein X is assumed to facilitate the

improper folding from a normal conformation into an abnormal prion. (Simmer, 2006)

When the disease is inherited, it is guaranteed to produce symptomatic response in the

later years of life. Conversely, when the disease is spread as an infectious agent it can be

acquired through eating contaminated beef from cattle that have bovine spongiform

encephalopathy or Mad Cow Disease. Finally, spontaneous CJD can occur with no apparent

cause, yet it is believed that a protein exists within the body in a transient structure. Once it

bonds to the misfolded PRPSC, it grows an affinity to fold in the mutated manner and lead to

neurodegeneration as the misfolded proteins aggregate and pass the blood brain barrier.

Conclusion

Observing cattle for the tell-tale behavioral signs can prevent the spread through

ingesting contaminated meats. Agricultural professionals should receive education on these

warning signs in order to mitigate the spread of this disease. In conclusion, all biological

molecules are formed in a similar methodology. Smaller elements or monomers combine into a

polymer, in the case of proteins amino acids are the monomer which combines to form the

polymer of a the polypeptide chain. This polypeptide chain will combine with one or more

polypeptide chains and finally fold into a protein structure. Proper folding will determine the

protein shape and function, while denaturation and aggregation occur when proteins fold
AMINO ACIDS & PEPTIDE BONDS, PROTEIN STRUCTURE 8

incorrectly. Incorrect folding of proteins can lead to an entire host of disease such as prion

disease.

Diagrams & Models

Model A.1

Model B.1

Diagram C.1-D.1
AMINO ACIDS & PEPTIDE BONDS, PROTEIN STRUCTURE 9
AMINO ACIDS & PEPTIDE BONDS, PROTEIN STRUCTURE 10

Reference

The Biology Project: Biochemistry. (2003). Leucine. Retrieved from

http://www.biology.arizona.edu/biochemistry/problem_sets/aa/Leucine.html

BSE info. (2015). Prion Definition. Retrieved from http://www.bseinfo.org/priondefinition.aspx

Green, H. (2012). Biological Molecules - You Are What You Eat: Crash Course Biology #3.

Crash Course Biology. Retrieved from https://www.youtube.com/watch?

v=H8WJ2KENlK0

Jones, G.W., & Tuite, M.F. (2005). Chaperoning prions: the cellular machinery for propagating

an infectious protein? . Bioessays. Retrieved from

http://eprintsprod.nuim.ie/530/1/Jones_%26_Tuite_revised-1GJ.pdf

Khan Academy. (2014). Chemical Processes: Proteins. Retrieved from

https://www.khanacademy.org/test-prep/mcat/chemical-processes/proteins

Kupfer, L., Hinrichs, W., & Groschup, M. (2009). Prion Protein Misfolding. Current Molecular

Medicine, 9(7), 826835. doi:10.2174/156652409789105543

New World Encyclopedia. (2014). Leucine. Retrieved from

http://www.newworldencyclopedia.org/entry/Leucine

Moulton, G.E. (2004) The Complete Idiot's Guide to Biology All rights reserved including the

right of reproduction in whole or in part in any form. Used by arrangement with Alpha

Books, a member of Penguin Group (USA) Inc. Retrieved from:

http://www.infoplease.com/cig/biology/proteins.html#ixzz3QkRHQhgc

Simmer, M. (2006). Prions: Infectious Proteins Responsible for Mad Cow Disease. The Science

Creative Quarterly. Retrieved from http://www.scq.ubc.ca/prions-infectious-proteins-

repsonsible-for-mad-cow-disease/
AMINO ACIDS & PEPTIDE BONDS, PROTEIN STRUCTURE 11

Vauquelin LN, & Robiquet PJ (1806). The discovery of a new plant principle in Asparagus

sativus". Annales de Chimie 57: 8893.