2.3: Protein

Protein is another major macronutrient that, like carbohydrates, are made up of small repeating units. But instead of sugars, protein is made up of amino acids. In the following sections, you will learn more about how protein is synthesized and why it is important in the body.

Amino Acids

Similar to carbohydrates, proteins contain carbon (\(\ce{C}\)), hydrogen (\(\ce{H}\)), and oxygen (\(\ce{O}\)). However, unlike carbohydrates (and lipids) proteins also contain nitrogen (\(\ce{N}\)). Proteins are made up of smaller units called amino acids. This name, amino acid, signifies that each contains an amino (\(\ce{NH2}\)) and carboxylic acid (\(\ce{COOH}\)) groups. The only structural difference in the 20 amino acids is the side group represented by the \(\ce{R}\) below.

Figure \(\PageIndex{1}\): Structure of an amino acid

To illustrate the differences in the side group we will consider glycine and alanine, the two simplest amino acids. For glycine the \(\ce{R}\) group is hydrogen (\(\ce{H}\)), while in alanine the \(\ce{R}\) group is a methyl (\(\ce{CH3}\)). The structures of these two amino acids are shown below.

Figure \(\PageIndex{2}\): Structure of glycine

Figure \(\PageIndex{3}\): Structure of alanine

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Individual amino acids are joined together using a peptide bond (green) and is shown in the figure below.

Figure \(\PageIndex{4}\): Peptide bond formation1

Amino acids can also come together to form tripeptides (three amino acids), oligopeptides (medium size peptide, there isn’t a formal cutoff), and polypeptides (large size). A polypeptide is a chain of amino acids as shown below.

Figure \(\PageIndex{5}\): A polypeptide chain2

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Protein Synthesis

The process of protein synthesis is not as simple as stringing together amino acids to form a polypeptide. As shown below, this is a fairly involved process. DNA contains the genetic code that is used as a template to create mRNA in a process known as transcription. The mRNA then moves out of the nucleus into the cytoplasm where it serves as the template for translation, where tRNAs bring in individual amino acids that are bonded together to form a polypeptide.

Figure \(\PageIndex{6}\): The process of creating a polypeptide3

Proteins, known as ribosomes, assist with translation. After translation, the polypeptide can be folded or gain structure as shown below and will be discussed in the next subsection (Protein Structure).

Figure \(\PageIndex{7}\): Protein synthesis and processing4

These videos do an excellent job of showing and explaining transcription and translation, respectively.

Video \(\PageIndex{1}\): Transcription is the process by which the information in DNA is copied into messenger RNA (mRNA) for protein production. https://www.youtube.com/watch?v=5MfSYnItYvg

Video \(\PageIndex{2}\): mRNA Translation. https://www.youtube.com/watch?v=8dsTvBaUMvw

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Protein Structure

Protein structure is the orientation of the amino acids within a protein. There are four levels of protein structure. Primary structure is the linear polypeptide chain. Secondary structure occurs when hydrogen bonding between amino acids in the same polypeptide chain causes the formation of structures such as beta-pleated sheets and alpha-helices. Tertiary structure occurs as a result of an attraction between different amino acids of the polypeptide chain and interactions between the different secondary structures. Finally, certain proteins contain quaternary structure where multiple polypeptide chains are bonded together to form a larger molecule. Hemoglobin is an example of a protein with quaternary structure. The figure below illustrates the different levels of protein structure.

Figure \(\PageIndex{8}\): Different Protein Structures5

This video does a nice job of illustrating and explaining the different protein structures.

Video \(\PageIndex{3}\): A short video about protein primary, secondary, tertiary and quaternary structure. https://www.youtube.com/watch?v=lijQ3a8yUYQ

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Protein Functions

There are various functions of proteins in the body that are described below.

Structural

Proteins, such as collagen, serve as the scaffolding of the body, and thus are important for the structure of tissues.

Figure \(\PageIndex{9}\): Triple-helix structure of collagen6

Enzymes

We will discuss a number of enzymes throughout this class, and the vast majority are proteins. An enzyme catalyzes (enhances the rate of) a chemical reaction. The key part of an enzyme is its "active site". The active site is where a compound to be acted on, known as a substrate, enters. Enzymes are specific for their substrates; they do not catalyze reactions on any random compounds floating by. You might have heard the "lock and key" analogy used for enzymes and substrates, respectively. After the substrate enters the active site and binds, the enzyme slightly changes shape (conformation). The enzyme then catalyzes a reaction that, in the example below, splits the substrate into two parts. The products of this reaction are released and the enzyme returns to its native or original shape. It is then ready to catalyze another reaction. The figure and video below nicely illustrate the function of an enzyme.

Figure \(\PageIndex{10}\): The function of enzymes7

Video \(\PageIndex{4}\): Enzymes allow many chemical reactions to occur within the homeostasis constraints of a living system. Enzymes function as organic catalysts. A catalyst is a chemical involved in, but not changed by, a chemical reaction. https://www.youtube.com/watch?v=cbZsXjgPDLQ

Enzymes’ names commonly end in -ase, and many are named for their substrate. For example the enzyme amylase cleaves bonds found in amylose and amylopectin.

Hormones

Many hormones are proteins. A hormone is a compound that is produced in one tissue, released into circulation, then has an effect on a different organ. Most hormones are produced from several organs, collectively known as endocrine organs. Insulin is an example of a hormone that is a protein. The video below describes and illustrates the functions of hormones.

Video \(\PageIndex{5}\): Many of the body's most basic functions are regulated by the endocrine system—eight different glands located throughout the body. The endocrine system constantly and quietly does its work—secreting liquid chemical messengers called hormones. https://www.youtube.com/watch?v=kIPYVV4aThM

Fluid Balance

Proteins help to maintain the balance between fluids in the plasma and the interstitial fluid. Interstitial fluid is the fluid that surrounds cells. Interstitial fluid and plasma (fluid part of blood) are the two components of extracellular fluid, or the fluid outside of cells. The following figure illustrates the exchange of fluid between interstitial fluid and plasma.

Figure \(\PageIndex{11}\): Interstitial Fluid and plasma8

Acid-Base Balance

Proteins serve as buffers, meaning that they help to prevent the pH of the body from getting too high or too low.

Transport

Transport proteins move molecules through circulation or across cell membranes. One example is hemoglobin that transports oxygen through the body. We will see a number of other examples as we move through class.

Immune Function

Antibodies are proteins that recognize antigens (foreign substances that generate antibody or inflammatory response) and bind to and inactivate them. Antibodies are important in our ability to ward off disease.

Other Functions

Proteins can also serve as neurotransmitters and can be used for energy by forming glucose through gluconeogenesis.

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Types of Amino Acids

There are 20 amino acids our body uses to synthesize proteins. These amino acids can be classified as essential, non-essential, or conditionally essential. The table below shows how the 20 amino acids are classified.

Table \(\PageIndex{1}\): Essential, conditionally essential, and nonessential amino acids9

Essential	Conditionally Essential	Nonessential
Histidine	Arginine	Alanine
Isoleucine	Cysteine	Asparagine
Leucine	Glutamine	Aspartic Acid or Aspartate
Lysine	Glycine	Glutamic Acid or Glutamate
Methionine	Proline	Serine
Phenylalanine	Tyrosine
Threonine
Tryptophan
Valine

The body cannot synthesize nine amino acids. Thus, it is essential that these are consumed in the diet. As a result, these amino acids are known as essential, or indispensable, amino acids. As an example of how amino acids were determined to be essential, Dr. William C. Rose at the University of Illinois discovered that threonine was essential by feeding different diets to graduate students at the university as described in the following link.

Web Link

Discovery of Threonine by William C. Rose

Nonessential, or dispensable, amino acids can be made in our body, so we do not need to consume them. Conditionally essential amino acids become essential for individuals in certain situations. An example of a condition when an amino acid becomes essential is the disease phenylketonuria (PKU). Individuals with PKU have a mutation in the enzyme phenylalanine hydroxylase, which normally adds an alcohol group (OH) to the amino acid phenylalanine to form tyrosine as shown below.

Figure \(\PageIndex{12}\): Phenylketonuria (PKU) results from a mutation in the enzyme phenylalanine hydroxylase10,11

Since tyrosine cannot be synthesized by people with PKU, it becomes essential for them. Thus, tyrosine is a conditionally essential amino acid. Individuals with PKU have to eat a very low protein diet and avoid the alternative sweetener aspartame, because it can be broken down to phenylalanine. If individuals with PKU consume too much phenylalanine, phenylalanine and its metabolites, can build up and cause brain damage and intellectual disabilities. The drug Kuvan was approved for use with PKU patients in 2007 who have low phenylalanine hydroxylase activity levels. You can learn more about this drug using the link below.

Web Link

Kuvan

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Amino Acid Structures

It is a good idea to have a general idea of the structure of the different amino acids and to be able to recognize them as amino acids. You are not expected to memorize these structures. Often I say the name of amino acids and not all students understand that I am talking about an amino acid. Each amino acid differs only by its side group, which is circled in red in each figure below. Also, the more familiar you become with chemical structures, the more prepared you will be for later classes.

Histidine¹²

Isoleucine¹³

Leucine¹⁴

Lysine¹⁵

Methionine¹⁶

Phenylalanine¹⁷

Threonine¹⁸

Tryptophan¹⁹

Valine ²⁰

Figure \(\PageIndex{13}\): Essential amino acids12-20

You may hear someone talk about the branch chain amino acids, which are all essential amino acids, but they are singled out in the figure below. These amino acids have branched carbons in their side chains.

Valine²⁰

Leucine¹⁴

Isoleucine¹³

Figure \(\PageIndex{14}\): Branched chain amino acids20,14,13

Arginine²¹

Cysteine²²

Glutamine²³

Glycine²⁴

Proline²⁵

Tyrosine²⁶

Figure \(\PageIndex{15}\): Conditionally essential amino acids21-26

Alanine²⁷

Asparagine²⁸

Aspartate (aspartic acid)²⁹

Glutamate (glutamic acid)³⁰

Serine³¹

Figure \(\PageIndex{16}\): Nonessential amino acids27-31

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References

1. en.Wikipedia.org/wiki/File:Pe...mationball.svg
2. http://www.genome.gov/Glossary/index.cfm?id=149
3. www.genome.gov/Pages/Hyperion...essenger%20RNA
4. en.Wikipedia.org/wiki/File:Pr...nsynthesis.png
5. "225 Peptide Bond-01" by OpenStax College - Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013.. Licensed under CC BY 3.0 via Commons - commons.wikimedia.org/wiki/F...de_Bond-01.jpg
6. en.Wikipedia.org/wiki/File:Co...riplehelix.png
7. en.Wikipedia.org/wiki/File:In...it_diagram.svg
8. en.Wikipedia.org/wiki/File:Il...irculation.jpg
9. Anonymous. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). Protein and Amino Acids. Institute of Medicine, Food and Nutrition Board. 2005 http://books.nap.edu/openbook.php?re...10490&page=589
10. en.Wikipedia.org/wiki/Phenyl...nylalanine.svg
11. en.Wikipedia.org/wiki/Tyrosi...L-Tyrosine.svg
12. en.Wikipedia.org/wiki/Histid..._Histidine.svg
13. en.Wikipedia.org/wiki/Isoleu...Isoleucine.svg
14. en.Wikipedia.org/wiki/Leucin...e_Nonionic.svg
15. en.Wikipedia.org/wiki/Lysine...D-skeletal.png
16. en.Wikipedia.org/wiki/Methio...Methionine.svg
17. en.Wikipedia.org/wiki/Phenyl...nylalanine.svg
18. en.Wikipedia.org/wiki/Threon...eonineasdf.png
19. en.Wikipedia.org/wiki/Trypto...Tryptophan.svg
20. en.Wikipedia.org/wiki/Valine...notatpH7.4.png
21. en.Wikipedia.org/wiki/Argini...-_Arginine.svg
22. en.Wikipedia.org/wiki/Cystei...L-Cysteine.svg
23. en.Wikipedia.org/wiki/Glutam...-Glutamine.svg
24. en.Wikipedia.org/wiki/Glycin..._-_Glycine.svg
25. en.Wikipedia.org/wiki/Prolin..._-_Proline.svg
26. en.Wikipedia.org/wiki/Tyrosi...L-Tyrosine.svg
27. en.Wikipedia.org/wiki/Alanin..._L-Alanine.svg
28. en.Wikipedia.org/wiki/Aspara...Asparagine.svg
29. en.Wikipedia.org/wiki/Aspart...tic_Acidph.png
30. en.Wikipedia.org/wiki/Glutam..._Non-ionic.png
31. en.Wikipedia.org/wiki/Serine...-_L-Serine.svg
32. Wardlaw GM, Hampl J. (2006) Perspectives in nutrition. New York, NY: McGraw-Hill.
33. commons.wikimedia.org/wiki/F...y_sandwich.jpg
34. en.Wikipedia.org/wiki/File:Re...s_and_rice.jpg
35. Young VR, Pellett PL. (1994) Plant proteins in relation to human protein and amino acid nutrition. Am J Clin Nutr. May; 59 (5 Suppl): 1203S-1212S.
36. Schaafsma G. (2000) The protein digestibility-corrected amino acid score. J Nutr 130(7): 1865S-1867S.
37. www.fao.org/ag/humannutrition...04ffc17f06.pdf
38. Rutherford SM, Fanning AC, Miller BJ, Moughan PJ. Protein Digestibility-Corrected Amino Acid Scores and Digestible Indispensable Amino Acid Scores Differentially Describe Protein Quality in Growing Male Rats. J Nutr. 145(2): 372-379.
39. Byrd-Bredbenner C, Moe G, Beshgetoor D, Berning J. (2009) Wardlaw's perspectives in nutrition. New York, NY: McGraw-Hill.
40. en.Wikipedia.org/wiki/File:Starved_girl.jpg
41. en.Wikipedia.org/wiki/File:Starved_child.jpg