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Course lecturer :

Jasmin Šutković

23 December 2015

Organic Chemistry – FALL 2015

Lecture 9AMINO ACIDS, PROTEINS, AND ENZYMES

CHAPTER OUTLINE International University of Sarajevo

21.1 Introduction21.2 Amino Acids21.3 Acid–Base Behavior of Amino Acids21.4 Peptides21.5 FOCUS ON THE HUMAN BODY:Biologically Active Peptides21.6 Proteins21.7 FOCUS ON THE HUMAN BODY:Common Proteins21.8 Protein Hydrolysis and Denaturation21.9 Enzymes21.10 FOCUS ON HEALTH & MEDICINE:Using Enzymes to Diagnose andTreat Diseases

Book chapter 21

Introduction

Proteins are biomolecules that contain many amide bonds, formed by joining amino acids together.

Introduction

The word protein comes from the Greek proteios meaning “of fi rst importance.”

Fibrous proteins, like keratin in hair, skin, and nails and collagen in connective tissue, give support and structure to tissues and cells.

Protein hormones and enzymes regulate the body’s metabolism/

Transport proteins carry substances through the blood, and storage proteins store elements and ions in organs.

Contractile proteins control muscle movements, and immunoglobulinsare proteins that defend the body against foreign substances

AMINO ACIDS

To understand protein properties and structure, we must first learn about the amino acids that compose them.

Amino acids contain two functional groups—an amino group (NH2) and a carboxyl group (COOH). In most naturally occurring amino acids, the amino group is bonded to the α carbon, the carbon adjacent to the carbonyl group, making them 𝛂-amino acids.

• All amino acids have common names, which are abbreviated by a three-letter or one-letter designation. For example, glycine is often written as the three-letter abbreviation Gly, or the one-letter abbreviation G. These abbreviations are also given in Table 21.2.

• Amino acids never exist in nature as neutral molecules with all uncharged atoms. Since amino acids contain a base (NH2 group) and an acid (COOH), proton transfer from the acid to the base forms a salt called a zwitterion, which contains both a positive and a negative charge.

• These saltshave high melting points and are water soluble.

• Humans can synthesize only 10 of the 20 amino acids needed for proteins. The remaining 10, called essential amino acids, must be obtained from the diet and consumed on a regular, almost daily basis.

• Diets that include animal products readily supply all of the needed amino acids.

STEREOCHEMISTRY OF AMINO ACIDS

Except for the simplest amino acid, glycine, all other amino acids have a chirality center—a carbon bonded to four different groups—on the carbon𝛂 .

Thus, an amino acid like alanine (R = CH3) has two possible enantiomers, drawn below in both three-dimensional representations with wedges and dashed bonds, and Fischer projections.

ACID–BASE BEHAVIOR OF AMINO ACIDS

As mentioned in Section 21.2, an amino acid contains both a basic amino group (NH2) and an acidic carboxyl group (COOH).

As a result, proton transfer from the acid to the base forms a zwitterion, a salt that contains both a positive and a negative charge.

The zwitterion is neutral; that is, the net charge on the salt is zero.

Thus, alanine exists in one of three different forms depending on the pH of the solution in which it is dissolved. At the physiological pH of 7.4, neutral amino acids are primarily in their zwitterionic forms.

The pH at which the amino acid exists primarily in its neutral form is called its isoelectric point, abbreviated as pI.

The isoelectric points of neutral amino acids are generally around 6.

PEPTIDES

When amino acids are joined together by amide bonds, they form larger molecules called peptides and proteins.

• A dipeptide has two amino acids joined together by one amide bond.

• A tripeptide has three amino acids joined together by two amide bonds

Fischer projection formulas are also used for compounds like aldohexoses that contain several chirality centers.

The letters D and L are used to label all monosaccharides, even those with many chirality centers.

The configuration of the chirality center farthest from the carbonyl group determines whether a monosaccharide is D or L

Polypeptides and proteins both have many amino acids joined together in long linear chains, but the term protein is usually reserved

for polymers of more than 40 amino acids.

FOCUS ON THE HUMAN BODYBIOLOGICALLY ACTIVE PEPTIDES

NEUROPEPTIDES—ENKEPHALINS for PAIN RELIEF

Enkephalins, pentapeptides synthesized in the brain, act as pain killers and sedatives by binding to pain receptors.

The addictive narcotic analgesics morphine and heroin (Section 18.5) bind to the same receptors as the enkephalins, and thus produce a similar physiologica response.

Enkephalins are related to a group of larger polypeptides called endorphins that contain 16–31 amino acids. Endorphins also block pain and are thought to produce the feeling of well-being experienced by an athlete after excessive or strenuous exercise.

FOCUS ON THE HUMAN BODYBIOLOGICALLY ACTIVE PEPTIDES

PEPTIDE HORMONES—OXYTOCIN AND VASOPRESSIN of calories per gram. Oxytocin and Vasopressin are cyclic nonapeptide hormones

secreted by the pituitary gland. Their sequences are identical except for two amino acids, yet this

is enough to give them very different biological activities.

Oxytocin and Vasopressin

Oxytocin stimulates the contraction of uterine muscles, and it initiates the flow of milk in nursing mothers (Figure 21.2). Oxytocin, sold under the trade names Pitocin and Syntocinon !

Vasopressin, also called anti-diuretic hormone (ADH), targets the kidneys and helps to keep the electrolytes in body fluids in the normal range. Vasopressin is secreted when the body is dehydrated and causes the kidneys to retain fluid, thus decreasing the volume of the urine

PROTEINS

To understand proteins, the large polymers of amino acids that are responsible for so much of the structure and function of all living cells, we must learn about four levels of structure, called the primary, secondary, tertiary, and quaternary structure of proteins.

PRIMARY STRUCTURE

The primary structure of a protein is the particular sequence of amino acids that is joined together by peptide bonds.

The most important element of this primary structure is the amide bond that joins the amino acids.

SECONDARY STRUCTURE

The three-dimensional arrangement of localized regions of a protein is called its secondary structure.

These regions arise due to hydrogen bonding between the N-H proton of one amide and the C-O oxygen of another.

Two arrangements that are particularly stable are called the 𝛂-helix and the -pleated sheet.𝛃

𝛂-helix

The 𝛂-helix forms when a peptide chain twists into a right-handed or clockwise spiral, as shown in figure.

α-helix

Several important features characterize an α-helix :

β-Pleated Sheet

The 𝛃-pleated sheet forms when two or more peptide chains, called strands, line up side-byside, as shown in Figure 21.5.

All β-pleated sheets have the following characteristics:

The C O and N H bonds lie in the plane of the sheet. Hydrogen bonding often occurs between the N H and C O

groups of nearby amino acid residues. The R groups are oriented above and below the plane of the

sheet, and alternate from one side to the other along a given strand.

TERTIARY AND QUATERNARY STRUCTURE

The three-dimensional shape adopted by the entire peptide chain is called its tertiary structure.

A peptide generally folds into a shape that maximizes its stability.

In addition, polar functional groups hydrogen bond with each other (not just water), and amino acids with charged side chains like –COO– and –NH3 + can stabilize tertiary structure by electrostatic interactions.

Finally, disulfide bonds are the only covalent bonds that stabilize tertiary structure

Celluloze

FOCUS ON THE HUMAN BODYCOMMON PROTEIN

Proteins are generally classified according to their three-dimensional shapes.

Fibrous proteins are composed of long linear polypeptide chains that are bundled together to form rods or sheets. These proteins are insoluble in water and serve structural roles, giving strength and protection to tissues and cells.

Globular proteins are coiled into compact shapes with hydrophilic outer surfaces that make them water soluble. Enzymes and transport proteins are globular to make them soluble in blood and other aqueous environments.

α-KERATINS

𝛂-Keratins are the proteins found in hair, hooves, nails, skin, and wool.

They are composed almost exclusively of long sections of α-helix units, having large numbers of alanine and leucine residues.

Since these nonpolar amino acids extend outward from the α-helix, these proteins are very insoluble in water.

Two α-keratin helices coil around each other, forming a structure called a supercoil or superhelix

COLLAGEN

Collagen, the most abundant protein in vertebrates, is found in connective tissues such as bone, cartilage, tendons, teeth, and blood vessels.

Glycine and proline account for a large fraction of its amino acid

residues.

Collagen forms an elongated left-handed helix, and then three of these helices wind around each other to form a right-handed superhelix or triple helix.

Two views of the collagen superhelix are shown in Figure 21.13.

HEMOGLOBIN AND MYOGLOBIN

Hemoglobin and myoglobin, two globular proteins, are called conjugated proteins because they are composed of a protein unit and a nonprotein molecule.

In hemoglobin and myoglobin, the nonprotein unit is called heme, a complex organic compound containing the Fe2+ ion complexed with a large nitrogen-containing ring system.

The Fe2+ ion of hemoglobin and myoglobin binds oxygen.

Hemoglobin, which is present in red blood cells, transports oxygen to wherever it is needed in the body, whereas myoglobin stores oxygen in tissues.

Sickle cell anemia

Is a hereditary blood disorder, characterized by red blood cells that assume an abnormal, rigid, sickle shape.

Sickling decreases the cells' flexibility and results in a risk of various complications.

The sickling occurs because of a mutation in the haemoglobin gene. Individuals with one copy of the defunct gene display both normal and abnormal haemoglobin!

PROTEIN HYDROLYSIS AND DENATURATION

The properties of a protein are greatly altered and often entirely destroyed when any level of protein structure is disturbed.

PROTEIN HYDROLYSIS The hydrolysis of the amide bonds in a protein forms the

individual amino acids that comprise the primary structure.

PROTEIN DENATURATION

Denaturation is the process of altering the shape of a protein without breaking the amide bonds that form the primary structure.

High temperature, acid, base, and even agitation can disrupt the non-covalent interactions that hold a protein in a specific shape.

As a result, denaturation causes a globular protein to uncoil into an undefined randomly looped structure.

ENZYMES

We conclude the discussion of proteins with enzymes, proteins that serve as biological catalysts for reactions in all living organisms.

Enzymes are crucial to the biological reactions that occur in the body, which would otherwise often proceed too slowly to be of any use. In humans, enzymes must catalyze reactions under very specific physiological conditions, usually a pH around 7.4 and a temperature of 37 °C.

CHARACTERISTICS OF ENZYMES

Enzymes greatly enhance reaction rates. An enzyme-catalyzed reaction can be 106 to 1012 times faster than a similar uncatalyzed reaction.

Enzymes are very specific.

Example : carboxypeptidase A, digestive enzyme that breaks down proteins, catalyzes the hydrolysis of a specific type of peptide bond—the amide bond closest to the C-terminal end of the protein.

Coenzyme and cofactors

A cofactor is a metal ion or a nonprotein organic molecule needed for an enzymecatalyzed reaction to occur.

An organic compound that serves as an enzyme cofactor is called a coenzyme

HOW ENZYMES WORK

An enzyme contains a region called the active site that binds the substrate, forming an enzyme – substrate complex.

In biochemistry, a substrate is a molecule upon which an enzyme acts !

E + S ES → EP E + P⇌ ⇌

Example – lock and key model

Two models have been proposed to explain the specificity of a substrate for an enzyme’s active site: the lock-and-key model and the induced-fit model.

In the lock-and-key model, the shape of the active site is rigid!

Other example – induced fit model

In the induced-fit model, the shape of the active site is more flexible.

ENZYME INHIBITORS

Some substances bind to enzymes and in the process, greatly alter or destroy the enzyme’s activity

An inhibitor is a molecule that causes an enzyme to lose activity.

An inhibitor can bind to an enzyme reversibly or irreversibly.

• A reversible inhibitor binds to an enzyme but then enzyme activity is restored when the inhibitor is released.

• An irreversible inhibitor covalently binds to an enzyme, permanently destroying its activity.

ZYMOGENS

Sometimes an enzyme is synthesized in an inactive form, and then it is converted to its active form when it is needed. The inactive precursor of an enzyme is called a zymogen or proenzyme