ABSALON_BioChem_Protein and Amino Acid Metabolism.pptx
1. Presented by:
RONNIE M. ABSALON, JR.
PhD Science Education
BIOLOGICAL CHEMISTRY
Protein & Amino Acid Metabolism
2. Topics to be
discussed
•Protein and Amino Acid : Overview
•Protein and Amino Acid Metabolism
•Describe how the body digests proteins
•Explain how protein can be used for energy
3. Proteins
• Proteins are biological macromolecules and one of the four
most important in living organisms.
• When you think of proteins, the first thing that comes to
mind might be protein-rich foods: lean chicken, lean pork,
eggs, cheese, nuts, beans, etc. However, proteins are so
much more than that. They are one of the most fundamental
molecules in all living organisms. They are present in every
single cell in living systems, sometimes in numbers larger
than a million, where they allow for various essential
chemical processes, for instance, DNA replication.
• Proteins are complex molecules due to their structure.
4. Proteins
• Proteins are complex biological macromolecules with
amino acids as basic units.
• Proteins form in condensation reactions of amino acids,
which join together by covalent bonds called peptide
bonds. Polypeptides are molecules composed of more
than 50 amino acids. Proteins are polypeptides.
• Fibrous proteins are structural proteins responsible for
the firm structures of various parts of cells, tissues and
organs. Examples include collagen, keratin and elastin.
5. Proteins
• Globular proteins are functional proteins. They act
as enzymes, carriers, hormones, receptors, and much
more. Examples are haemoglobin, insulin, actin and amylase.
• Membrane proteins are found in plasma membranes (cell
surface membranes). They serve as enzymes, facilitate cell
recognition, and transport the molecules during active and
passive transport. There are integral and peripheral
membrane proteins.
• Proteins are tested with a biuret test, using a biuret reagent,
a solution that determines the presence of peptide bonds in a
sample. A positive result is a change in colour from blue to
purple.
6. The Structure of Proteins
The basic unit in the protein structure is an amino
acid. Amino acids join together by covalent peptide
bonds to form polymers called polypeptides.
Polypeptides are then combined to form proteins.
Therefore, you can conclude that proteins are
polymers composed of monomers that are amino acids.
7. Amino Acids
An amino acid is a group
of organic molecules with
an amino group (-NH2),
a carboxyl group (-
COOH), and a side chain
(called R group) unique to
every amino acid. Each
amino acid molecule has
a central carbon C atom
to which the amino and
carboxyl groups are
attached.
8. Amino Acids
Amino acids are organic compounds composed
of five parts:
• the central carbon atom, or the α-carbon
(alpha-carbon)
• amino group -NH2
• carboxyl group -COOH
• hydrogen atom -H
• R side group, which is unique to each amino
acid.
There are 20 amino acids naturally found in
proteins, and each one has a different R
group. Figure 1. shows the general structure of
amino acids, and in figure 2. you can see how
the R group differs from one amino acid to
another.
9.
10. • Did you know that the average human adult requires around
1.0 to 1.2 grams of protein per kilogram of body weight,
depending on body composition?
• Because proteins are responsible for many life-sustaining
functions, protein undernutrition can lead to stunting,
physical weakness, and impaired immunity.
• Our body digests and utilizes proteins in the form of amino
acids. It also synthesizes proteins and nitrogen-containing
compounds like hormones and nucleotide bases using amino
acids present in the body. Such processes are collectively
referred to as amino acid metabolism.
Protein & Amino Acid Metabolism
11. Protein & Amino Acid Metabolism
• Alongside carbohydrates, fats, and nucleic
acids, proteins are one of the organic molecules that make
up most life forms. They are responsible for catalyzing most
of the chemical reactions that take place in the cell. They
provide cells with a lot of their structural components and
aid in binding cells into tissues.
• Protein is typically digested and absorbed in the form
of amino acids.
• There are 20 different types of amino acids that constitute
proteins, and the sequence of amino acids determines the
structure and properties of the resulting protein.
12. Protein & Amino Acid Metabolism
• Recall that metabolism refers to the chemical reactions that take place in
living organisms to provide energy for life-sustaining processes and to
synthesize new organic materials. Now, let's look at the definition of amino
acid metabolism.
• Amino acid metabolism refers to the sum of all chemical reactions in
which amino acids are broken down and synthesized for vital processes in
the body.
• Amino acids can be divided into two types: essential and non-
essential amino acids.
• Essential amino acids are amino acids necessary for an organism's
survival. Since we cannot synthesize these essential amino acids by
ourselves, we must obtain them from our diets.
• Non-essential amino acids are amino acids that can be synthesized by
the body.
14. Protein & Amino Acid Metabolism
• Now, did you know that not all the amino acids required for
the body's biological processes need to be ingested through
food?
• After completing their lifespan, proteins already present in
the metabolism can be recycled!
• Cellular amino acid pools are constantly being partially
drained and refilled as the body synthesizes and
degrades proteins.
• The replacement of older proteins as they degrade within the
cell is referred to as protein turnover.
15. Protein & Amino Acid Metabolism
• In a healthy adult human, around 300-600g of protein are
broken down and synthesized each day. Protein turnover
allows not only for variations in the amount
of proteins synthesized in accordance with the physiological
needs of the body but also for the removal of dysfunctional
proteins.
• Depending on the specific role they perform, proteins have
different rates of turnover. For example, enzymatic proteins
tend to have a shorter life span to better adapt to the body's
metabolic needs whereas, structural proteins typically have
longer half-lives (in the range of years).
16. Protein & Amino Acid Metabolism
• Once proteins have been broken down, free amino acids combine
with the non-essential amino acids produced in the liver and those
recycled from the body’s own proteins, constituting the amino acid
pool that is accessible for metabolic processes.
• Free amino acids can be used in two major ways:
• They can be used in synthesizing protein and other nitrogen-
containing compounds like nucleotide bases, neurotransmitters,
and hormones.
• The carbon skeletons of amino acids can also be oxidized and then
utilized as an energy source or used for glucose
synthesis during hypoglycemia (a state of having low glucose
levels in the blood).
17. Protein & Amino Acid Metabolism
• Unlike fats and carbohydrates, there is no dedicated storage of
proteins and amino acids in the human body. If not used
for biological processes, excess amino acids in the body are
typically degraded, and the nitrogen is expelled as urea. However,
the body can conserve protein when in a state of nutrient
deficiency or withdrawal.
18. Metabolic Classification of Amino Acids
• Amino acid metabolism starts with a protein being broken down into
amino acids, which are the building blocks for protein synthesis. Then,
these amino acids can undergo an important reaction involved in amino
acid metabolism called transamination. The major organ responsible for
transamination reactions is the liver.
• In transamination, a nitrogen-containing amino group (from an amino
acid) gets transferred to an acceptor keto acid (an alpha-ketoglutarate),
forming an amino acid glutamate and a keto acid pyruvate.
• A keto acid is an organic compound with a carboxylic acid (-COOH) and a
ketone group (a carbonyl group C=O bonded to other carbon atoms or
hydrocarbon radicals).
• An example of a transamination reaction converting alanine into glutamic
acid. The enzyme used in this reaction is called alanine transaminase
(ALT).
19. Metabolic Classification of Amino Acids
• After, glutamic acid undergoes a process called oxidative deamination,
where the amino group gets removed, and the amino acid gets utilized for
energy. This process produces ammonia, which is converted into urea for
renal excretion.
• Amino acids can also be classified based on the pathways involved in their
degradation:
• Glucogenic amino acids are those whose carbon skeletons are converted
into pyruvate or another citric acid cycle (TCA cycle) intermediate.
• Ketogenic amino acids are those whose carbon skeletons are converted
into acetyl-CoA or acetoacetyl-CoA, both of which are used to produce
ketone bodies. Leucine and lysine are the only amino acids that are
purely ketogenic. Their degradation yields acetyl-CoA and acetoacetyl-CoA.
20. Amino Acids Metabolism Enzyme
• Enzymes are special types of proteins that catalyze or
accelerate biochemical reactions without getting used up in
the reaction.
• A chain of enzymes can catalyze a series of reactions
called pathways to synthesize or breakdown
complex biological molecules.
• Enzymes are involved in both the synthesis and degradation
of amino acids. It is also involved in the coordination of the
reactions involved in protein synthesis and in the production
of urea.
• Problems with enzyme pathways involved in amino acid
metabolism can lead to amino acid disorders.
21. Amino Acids Metabolism Disorders
• Amino Acid Disorders (AAs) are diseases
brought on by dysfunctional enzymes.
People with amino acid disorders have
trouble breaking down some amino acids
because of missing or inactive enzymes.
These amino acids, as well as other toxic
substances, then accumulate in the body
and cause issues.
22. Amino Acids Metabolism Disorders Treatments
Phenylketonuria (PKU)
• Phenylketonuria is a hereditary amino acid metabolism disorder where
the body cannot process the amino acid phenylalanine to
make tyrosine due to a mutation in the enzyme phenylalanine
hydroxylase. When phenylalanine levels are too high, the brain can be
damaged and cause severe intellectual disability.
• Because of this risk, babies born in US hospitals are typically screened for
PKU, allowing for early detection and treatment.
• Those with PKU are typically required to have a low-protein diet.
Newborns are prescribed a special formula, while older children and
adults are recommended a diet that consists mostly of fruits, vegetables,
and low-protein bread, pasta, and cereals.
• Most babies that get on this strict diet soon after they are born eventually
develop normally and show no symptoms of PKU.
23. Amino Acids Metabolism Disorders Treatments
• Argininosuccinic Aciduria (ASA)
• Argininosuccinic aciduria is a disorder where the enzyme argininosuccinate lyase is
dysfunctional or missing.
• Argininosuccinate lyase is responsible for starting the reaction in which the amino acid arginine
is synthesized from argininosuccinate, a molecule that carries the nitrogenous waste collected
in the urea cycle. Arginine breaks down into ornithine, which initiates the urea cycle, and urea,
which is excreted.
• Because the enzyme argininosuccinate lyase (ASL) is dysfunctional or missing, arginine is not
synthesized, and nitrogen is not expelled. Excess nitrogen can then accumulate in the blood in
the form of ammonia, which can be toxic at high levels.
• Symptoms of ASA include drowsiness, little appetite, breathing problems, seizures, and
unusual body movements.
• This disease is fatal, so babies with ASA who are left untreated can die within the first few
weeks of life.
• Fortunately, most cases of ASA can be detected shortly after birth by screening.
• Treatment for ASA can range from the recommendation of low-protein, nitrite-rich foods to the
intake of large amounts of exogenous arginine, which will promote the synthesis of
argininosuccinate.
24. Amino Acids Metabolism Disorders Treatments
• Argininosuccinic Aciduria (ASA)
• Argininosuccinic aciduria is a disorder where the enzyme argininosuccinate lyase is
dysfunctional or missing.
• Argininosuccinate lyase is responsible for starting the reaction in which the amino acid arginine
is synthesized from argininosuccinate, a molecule that carries the nitrogenous waste collected
in the urea cycle. Arginine breaks down into ornithine, which initiates the urea cycle, and urea,
which is excreted.
• Because the enzyme argininosuccinate lyase (ASL) is dysfunctional or missing, arginine is not
synthesized, and nitrogen is not expelled. Excess nitrogen can then accumulate in the blood in
the form of ammonia, which can be toxic at high levels.
• Symptoms of ASA include drowsiness, little appetite, breathing problems, seizures, and
unusual body movements.
• This disease is fatal, so babies with ASA who are left untreated can die within the first few
weeks of life.
• Fortunately, most cases of ASA can be detected shortly after birth by screening.
• Treatment for ASA can range from the recommendation of low-protein, nitrite-rich foods to the
intake of large amounts of exogenous arginine, which will promote the synthesis of
argininosuccinate.
25. How the body digests proteins?
• Much of the body is made of protein, and these proteins take on a myriad of forms.
They represent cell signaling receptors, signaling molecules, structural members,
enzymes, intracellular trafficking components, extracellular matrix scaffolds, ion
pumps, ion channels, oxygen and CO2 transporters (hemoglobin). That is not even
the complete list! There is protein in bones (collagen), muscles, and tendons; the
hemoglobin that transports oxygen; and enzymes that catalyze all biochemical
reactions. Protein is also used for growth and repair.
• Amid all these necessary functions, proteins also hold the potential to serve as a
metabolic fuel source. Proteins are not stored for later use, so excess proteins must
be converted into glucose or triglycerides, and used to supply energy or build energy
reserves. Although the body can synthesize proteins from amino acids, food is an
important source of those amino acids, especially because humans cannot
synthesize all of the 20 amino acids used to build proteins.
26. How the body digests proteins?
The digestion of proteins begins in the stomach. When protein-rich foods enter the
stomach, they are greeted by a mixture of the enzyme pepsin and hydrochloric acid
(HCl; 0.5 percent). The latter produces an environmental pH of 1.5–3.5 that denatures
proteins within food. Pepsin cuts proteins into smaller polypeptides and their
constituent amino acids. When the food-gastric juice mixture (chyme) enters the small
intestine, the pancreas releases sodium bicarbonate to neutralize the HCl. This helps
to protect the lining of the intestine. The small intestine also releases digestive
hormones, including secretin and CCK, which stimulate digestive processes to break
down the proteins further. Secretin also stimulates the pancreas to release sodium
bicarbonate. The pancreas releases most of the digestive enzymes, including the
proteases trypsin, chymotrypsin, and elastase, which aid protein digestion. Together,
all of these enzymes break complex proteins into smaller individual amino acids,
which are then transported across the intestinal mucosa to be used to create new
proteins, or to be converted into fats or acetyl CoA and used in the Krebs cycle.
28. How the body digests proteins?
• In order to avoid breaking down the proteins that make up the pancreas and small
intestine, pancreatic enzymes are released as inactive proenzymes that are only
activated in the small intestine. In the pancreas, vesicles
store trypsin and chymotrypsin as trypsinogen and chymotrypsinogen.
• Once released into the small intestine, an enzyme found in the wall of the small intestine,
called enterokinase, binds to trypsinogen and converts it into its active form, trypsin.
Trypsin then binds to chymotrypsinogen to convert it into the active chymotrypsin.
Trypsin and chymotrypsin break down large proteins into smaller peptides, a process
called proteolysis.
• These smaller peptides are catabolized into their constituent amino acids, which are
transported across the apical surface of the intestinal mucosa in a process that is
mediated by sodium-amino acid transporters. These transporters bind sodium and then
bind the amino acid to transport it across the membrane.
• At the basal surface of the mucosal cells, the sodium and amino acid are released. The
sodium can be reused in the transporter, whereas the amino acids are transferred into
the bloodstream to be transported to the liver and cells throughout the body for protein
synthesis.
29. How the body digests proteins?
• Freely available amino acids are used to create proteins. If amino acids
exist in excess, the body has no capacity or mechanism for their storage;
thus, they are converted into glucose or ketones, or they are decomposed.
Amino acid decomposition results in hydrocarbons and nitrogenous
waste. However, high concentrations of nitrogen are toxic. The urea cycle
processes nitrogen and facilitates its excretion from the body.
30. References
1.Michael Reddy, Amino Acid | Definition, Structure, and Facts, Encyclopedia Britannica, 22 Aug. 2022.
2.Kevin Ahern and Indira Rajagopal, 7.7: Amino Acid Metabolism, Biology LibreTexts, 26 Feb. 2016.
3.McMurry et al, 25.2: Amino Acid Metabolism - an Overview, Chemistry LibreTexts, 5 Aug. 2017.
4.University of Arizona Department of Molecular & Cellular Biology, Amino Acids, Accessed 14 Oct. 2022.
5.NYU School of Medicine, Amino Acid Metabolism: Introduction, Accessed 14 Oct. 2022.
6.University of Nevada, Reno School of Medicine, Amino Acid Metabolic Disorders, Accessed 14 Oct.
2022.
7.MedlinePlus, Phenylketonuria, 22 Nov. 2016.
8.MedlinePlus Genetics, Argininosuccinic Aciduria, 1 Mar. 2020.
9.Gerald Litwack, Chapter 13 - Metabolism of Amino Acids, Human Biochemistry, 2018.
10.P. Newsholme, L. Stenson, M. Sulvucci, R. Sumayao, M. Krause, 1.02 - Amino Acid Metabolism,
2011.
11.Guoyao Wu, Dietary Protein Intake and Human Health, PubMed, 1 Mar. 2016.
12.https://www.studysmarter.co.uk/explanations/biology/biological-processes/amino-acid-metabolism/
13.https://courses.lumenlearning.com/suny-ap2/chapter/protein-
metabolism/?fbclid=IwAR0J95QP3D2Tn2DJL2-d0aZzLyjINjq5lu7DinA18e5ixHnpU956wVSXuUI