Chapter 6 CC1 book -to promote denatura>on of the proteins

Proteins and to catalyze their hydrolysis into polypep>des.

-are large, complex molecules comprised of 200 to 300 Small intes@ne
amino acids. -Sodium bicarbonate neutralizes HCl
-secreted by the pancreas under the direc>on of
Amino acids secre@n.
-are simple organic compounds that serve as the -in order to protect the intes>nal lining.
building blocks of proteins.
-but they are also used in the synthesis of nitrogen- Secre@n and Cholecystokinin is secreted by the small
containing non-protein compounds such as purines, intes>ne to s>mulate the release of proteoly>c
pyrimidines, porphyrins, crea>ne, histamine, thyroxine, enzymes trypsin and chymotrypsin, from the pancreas
epinephrine, and coenzyme NAD. and bile from the gall bladder.
-They differ from one another by the chemical trypsin and chymotrypsin
composi>on of their R-group. -They con>nue the process of
diges>on by hydrolyzing polypep>des intro
tripep>de, dipep>des, and cons>tuent
amino acids.
dipep@des, tripep@de, and amino acids
-are absorbed in the intes@nal lumen
through several cotransporters.

Carrier proteins
-in the luminal surface of the epithelial cell bind with an
ions, such as Hydrogen, sodium, and a dipep>de,
BASIC STRUCTURE tripep>de, and amino acids, which are then transported
Amino acid (is classified as Zwi?erion since they have into the cell.
neutral, posi>ve, and nega>ve func>onal groups, but
their net charge is neutral.) Pep@dase
-1 amino group (-NH2) -cleave any remaining pep>de bonds resul>ng in free
-can accept proton (basic) forming -NH3- amino acids.
-1 carboxyl func>onal group (-COOH)
-can donate proton (acidic) forming -COO- Facilita@ve transporters
-α-carbon -on the basolateral surface of the epithelial cell
-R group (side chain) -allow transport of amino acids into the blood stream,
where they will be transported to the liver via the
Note: Amino acids are amphoteric they have acidic and hepa@c portal vein.
basic tendencies.
Liver
Pep@de bond -where the amino acids will be used to synthesize new
-Formed from the link between the amino group of one proteins and nonprotein nitrogen compounds or be
amino acid and the carboxyl group of another amino used to generate energy through gluconeogenesis or
acid. ketogenesis.

Polypep@de
-Formed when a chain of amino acid is linked by pep>de
bonds.
-Large polypep>de cons>tute a protein.

Note: Proteins in human plasma cons>tute about 100

to 150 amino acids in the length of their polypep>de
chains.
:The content and arrangement of amino acids in a
specific protein are determine by the sequence of
nucleo>de bases in the gene that encodes for that
protein.

METABOLISM
Stomach
-Gastrin s>mulates the secre>on of HCl and proteoly>c
enzymes such as pepsin.
CLASSIFICATION
Essen@al amino acids
His@dine -Help grow and repair body >ssues
-To maintain the myelin sheaths that protect nerve cells
-Serve as precursor for several hormones and metabolites essen>al to renal, gastric, and immune
func>on (e.g. Histamine)
-Plays an important role in the synthesis of red and white blood cells, in protec>ng the body from
heavy metal toxicity.
-A source of carbon atoms in the synthesis of purine for DNA and RNA synthesis.

Isoleucine -Concentrated in muscle >ssues

-Essen>al for wound healing, immune func>on, glucose homeostasis, and hemoglobin forma>on.

Leucine -Regula>on of blood and glucose and would healing

-Preven>on of muscle protein degrada>on subsequent to trauma.

Valine -aids in determining the ter>ary structure of proteins

-promotes mental health and muscle coordina>on.

Lysine produc>on of an>bodies

-required for maintaining healthy >ssues.
-helps in absorp>on and conserva>on of calcium and serves an important role in the forma>on of
collagen.

Methionine -Helps to ini>ate transla>on of mRNA

-Stabilizes protein structure
-Important cellular an>oxidant
-an important source of sulfur
-assists in breakdown of fats
-helps detoxify lead and other heavy metals
-helps diminish muscle weakness
-Prevents briXle hair
-Reacts with ATP in the synthesis of epinephrine and choline.

Phenylalanine -A metabolic precursor of tyrosine.

Tyrosine is the precursor for neurotransmiXers dopamine, norepinephrine, and epinephrine,
collec>vely referred to as catecholamines.
Catecholamines
-perform several important roles in maintaining homeostasis through the autonomic nervous
system.
-Promo>ng alertness and vitality, eleva>ng mood, decreasing pain, and aiding in memory
learning.

Threonine -important component for forma>on of collagen, elas>n, and tooth enamel.
-important in produc>on of neurotransmiXers and overall health of the nervous system.
-Helps maintain proper protein balance in the body
-aid in liver func>on
-assists in metabolism of porphyrins and fats

Tryptophan -Metabolic precursor for serotonin and melatonin, which regulates appe>te, mood, sleep, and pain.
-Is a natural relaxant that helps alleviate insomnia by inducing sleep, soothes anxiety, and reduce
depression.
-An essen>al for produc>on of niacin

Nonessen@al Amino acids

Alanine -A product of the breakdown of DNA, anserine, and carnosine.
-Formed as a result of glycolysis in muscle >ssue and the conversion of pyruvate
-Play a major role in transfer of nitrogen from peripheral >ssue to the liver for processing and
excre>on.
-Strengthen the immune system through produc>on of an>bodies.
 -Serve as source of energy for the central nervous system, brain, and muscle >ssues.
-Helps in reducing the buildup of toxic substances released when muscle protein is broken down.

Asparagine -Derived from aspar>c acid and ATP through transamida@on.

Transamida@on
-An amide group is transferred from one compound to another.
-Is one of the principal and most abundant amino acids involved in the transport of nitrogen.
-required by the nervous system.
-Play an important role in the synthesis of ammonia.
-Primary func>on: The conversion of one amino acid into another via amina>on or
transamina>on.
Amina@on
-The process by which an amine group is introduced into an organic molecule
Transamina@on
-Is the transfer of an amino acid to and α-ketoacid.
Aspar@c -is synthesized from oxaloacetate through transamina>on in the citric acid cycle and the urea
acid/Aspartate cycle.
-important role of aspar>c acid is to serve as the precursor for several other amino acids, such as
asparagine, arginine, lysine, methionine, threonine, and isoleucine, as well as several nucleo>des.
-serves as a neurotransmiXer
-It also serves as a neurotransmiXer and par>cipates in the genera>on of glucose from non-
carbohydrate substrates, a process known as gluconeogenesis.
Glutamic -is produced from the transamina>on of amino acids such as alanine and aspar>c acid.
acid/Glutamate -serves as a neurotransmiXer and has an important role in the metabolism of carbohydrates and
fats as well as facilita>ng amino acid synthesis and degrada>on.
Selenocysteine - is not coded for directly in the gene>c code.
-it is encoded by a UGA codon, which is normally a stop codon; however, like the other amino
acids used by cells, selenocysteine has a specialized transfer RNA (tRNA).
-selenium analogue of cysteine, in which a selenium atom replaces sulfur.
-is present in several enzymes, such as formate dehydrogenases, glycine reductases, and some
hydrogenases.
Serine -synthesized from 3-phosphoglycerate, which is an intermediate in glycolysis.
-needed for the proper metabolism of lipids and faXy acids.
-plays an important role in the synthe>c pathways for pyrimidines, purines, crea>ne, and
porphyrins.
-It is highly concentrated in all cell membranes, serves as a component of the protec>ve myelin
sheaths surrounding nerve fibers, and aids in the produc>on of an>bodies.

Condi@onally Essen@al Amino Acids

Arginine -a complex amino acid o\en found at the cataly>c site in proteins and enzymes due to its amine-
containing side chain.
-plays an important role in:
-Cell division
-Wound healing
-S>mula>on of protein synthesis
-immune func>on
-Release of hormones
-Another important role of arginine is in the conversion of ammonia into urea.
Cysteine -Cysteine is poten>ally toxic, so it is absorbed during diges>on as cys>ne, which is more stable in
the gastrointes>nal tract and less toxic.
-Cys>ne is transported to cells, where it is reduced to two cysteine molecules upon cell entry.
-Cysteine can also be synthesized in vivo from methionine through a series of enzyma>c reac>ons.
-an important structural and func>onal component of many proteins.
-It is found in beta-kera>n and is important in collagen forma>on.
-It also has an>oxidant proper>es and involvement in metabolism of other molecules.
Glutamine -is synthesized from glutamic acid through the addi>on of an ammonia group and can donate the
ammonia group to form urea, which is excreted by the kidneys.
-plays an integral role in regula>on of ammonia, which is considered a toxic substance.
- renal maintenance of the acid–base balance.
-providing fuel for a healthy diges>ve tract.
 -ac>ng as the basis of the building blocks for synthesis of RNA and DNA.
-a source of cellular energy and aids in immune func>on.
Glycine -synthesized from the amino acid serine.
-It is essen>al for synthesis of nucleic acids, bile acids, proteins, pep>des, purines, ATP, porphyrins,
hemoglobin, glutathione, crea>ne, bile salts, glucose, glycogen, and other amino acids.
-is also an inhibitory neurotransmiXer in the central nervous system and a metal-complexing agent.
-limits muscle degenera>on, improves glycogen storage, promotes healing, and is u>lized by the
liver in the detoxifica>on of compounds.
Proline -produced from glutamic acid and other amino acids.
-It serves as the precursor for hydroxyproline, which is manufactured into collagen, tendons,
ligaments, and cardiac >ssue.
-is also involved in wound healing, especially that of car>lage, and in the strengthening of joints,
tendons, and cardiac >ssue.
Tyrosine -is synthesized from phenylalanine and serves as a precursor for adrenal and thyroid hormones.
-s>mulates metabolism and the - nervous system, acts as a mood elevator, and aids in func>on of
the adrenal, thyroid, and pituitary glands.

AMINOACIDOPATHIES MS/MS methods are considered to have higher

-are a class of inborn errors of metabolism in which an specificity and greater sensi>vity allowing for detec>on
enzyme defect inhibits the body’s ability to metabolize of lower concentra>ons of amino acids and an earlier
certain amino acids. diagnosis.
Gene@c assays using DNA analysis may also be
Medical complica>on caused by aminoacidopathies. performed to aid in the diagnosis and detec>on of
Brain damage- due to the accumula>on of toxic amino carrier status in families with an inborn error of
acids or their by products in the blood and >ssues. metabolism.

Newborn screening tests are performed to aid in the

early diagnosis of numerous inborn error of
metabolism.

The abnormali>es exist either in

1. The ac@vity of a specific enzyme in the
metabolic pathway.
2. The membrane transport system for the
amino acid

METHOD OF ANALYSIS
Urine samples may be used for analysis of amino acids
to screen for disorders affec>ng amino acid transport.
Plasma samples can be used to diagnose and monitor
aminoacidopathies.
Amino acid concentra@ons may also be evaluated in
the inves>ga>on of condi>ons involving the liver,
endocrine glands, gastrointes>nal tract, and kidneys
and in pa>ent with severe burns, muscular, neurologic,
or neoplas>c diseases.
CSF may also be analyzed to aid in the diagnosis of
select neurotransmiXer disorders.
Blood samples
-must be drawn 6 to 8 hours of fas>ng to avoid the
effect of absorbed amino acids origina>ng from dietary
proteins.
-Should be collected in an heparinized tube.
-The plasma should be removed from the cell within 2
hours of collec>on.

HPLC couple with Tandem mass spectrometry (HPLC-

MS/MS) may be used to quan>tate amino acids and
their metabolites in the pa>ent sample.