Amino Acids & Proteins Flashcards
are the building blocks of proteins.
Amino acids
TRUE/FALSE: Cellular growth, repair, and maintenance
are all dependent on amino acids.
TRUE
The amino group of one
amino acid can be linked with the carboxyl group of another amino acid
Peptide bond
Dietary proteins that completely digest dietary proteins into their constituent amino acids.
Pepsin & trypsin
PVTTIMHALL:
arginine, histidine, isoleucine, leucine, lysine,
methionine, phenylalanine, threonine, tryptophan, and valine.
Essential amino acids
proteins provide up to ___% of the total energy
required daily by the body.
20
One important role is
the conversion of ammonia, which is highly toxic, into urea, which can be safely
excreted via the urinary system.
Arginine
needed to help grow and repair body tissues and to maintain the
myelin sheaths that protect nerve cells and is the direct precursor of histamine,
which is involved in immune response.
Histidine
are branched-chain amino acids that are
collectively referred to as the branched-chain amino acid group.
Isoleucine, leucine, and valine
plays an important role in hemoglobin formation,
isoleucine
necessary for optimal growth in infants.
leucine
also aid in
maintaining the nitrogen balance in adults.
Leucine and valine
used in treatments for
muscle, mental, and emotional problems such as insomnia and anxiety, as well as
liver and gallbladder disease.
Valine
It plays a role in the production of antibodies and lowering
triglyceride levels. helps in the absorption and conservation of
calcium and plays an important role in the formation of collagen
Lysine
is a source of sulfur, which is
required for normal metabolism and growth.
Methionine
uses an active transport channel to cross the blood–
brain barrier and is used by the brain to produce norepinephrine, a
neurotransmitter that transmits signals between nerve cells.
Phenylalanine
alcohol-containing amino acid that is an important component in
the formation of collagen, elastin (a connective tissue protein), and tooth enamel.
Threonine
metabolic precursor for serotonin, melatonin (a neurohormone), and niacin (a vitamin).
Tryptophan
one of the simplest amino acids and is a product of the breakdown of
DNA or the dipeptides, anserine and carnosine.
Alanine
plays a major role in
the transfer of nitrogen from peripheral tissues to the liver for processing and
excretion and strengthens the immune system through production of antibodies.
Alanine
one of the principal and most abundant amino acids involved in the transport of
nitrogen.
Asparagine
is the process by which an amine group is introduced into an organic
molecule,
Amination
is the transfer of an amino acid to an α-ketoacid.
transamination.
precursor for several
other amino acids. is a metabolite in the citric acid cycle and the urea
cycle. It also participates in the generation of glucose from nonsugar substrates,
Aspartic acid,
is an important structural and functional component of many proteins
and enzymes and has significant antioxidant properties.
Cysteine
serves as a neurotransmitter, and its
dysregulation has been linked to epileptic seizures. It is also important in the
metabolism of sugars and fats and aids in the transport of potassium into spinal
fluid.
Glutamic acid
the most abundant amino acid in the body and is synthesized from
glutamic acid.
Glutamine
synthesized from another nonessential amino acid, serine.
Glycine
involved in wound healing, especially that of cartilage, and in
the strengthening of joints, tendons, and cardiac tissue. It also works in tandem
with vitamin C to promote healthy connective tissues.
Proline
needed for the proper metabolism of lipids and fatty acids
and plays an important role in the body’s synthetic pathways for pyrimidines,
purines, creatine, and porphyrins.
Serine
precursor of the adrenal hormones epinephrine, norepinephrine, and dopamine
and thyroid hormones including thyroxine. It is important in overall metabolism
and aiding in function of the adrenal glands, thyroid, and pituitary glands.
Tyrosine
recognized as the 21st amino acid; encoded by a UGA codon; has a
specialized transfer RNA (tRNA).
Selenocysteine
the 22nd naturally occurring genetically encoded amino acid used
by some prokaryotes and single-celled microorganisms in enzymes that are part
of their methane-producing metabolism. This amino acid is not present in humans.
Pyrrolysine
are a class of inherited errors of metabolism in which there is an enzyme defect that inhibits the body's ability to metabolize certain amino acids.
Aminoacidopathies
one of the most well-known aminoacidopathies and
was the first newborn screening test introduced in the early 1960s.
Phenylketonuria (PKU)
absence of activity of the enzyme phenylalanine hydroxylase (PAH) due to
mutations in the PAH gene.
PKU
In the newborn, the upper limit of normal
for phenylalanine concentration in the blood is
120 μmol/L (2 mg/dL).
In the
absence of PAH activity, phenylalanine concentrations are usually greater than
1,200 μmol/L
can also be the result of a deficiency in the enzymes
needed for regeneration and synthesis of tetrahydrobiopterin (BH4)
Hyperphenylalaninemia
cofactor required for the enzymatic hydroxylation of phenylalanine, tyrosine,
and tryptophan.
BH4
the first drug to help manage PKU.
14
The drug helps reduce phenylalanine concentrations by increasing the activity of
the PAH enzyme.
sapropterin dihydrochloride (Kuvan®),
semiquantitative, bacterial inhibition assay for
phenylalanine based on the ability of phenylalanine to facilitate bacterial growth
in a culture medium despite the presence of a growth inhibitor.
Guthrie test
an agar gel plate containing _____ , a growth inhibitor,
is inoculated with Bacillus subtilis.
β-2-thienylalanine,
The Guthrie test is sensitive enough to detect serum
phenylalanine concentrations of
180 μmol/L (3 mg/dL).
The reference method for quantitative serum phenylalanine is _____;
however, _____ is now considered to be the gold standard for detecting a
variety of congenital diseases in newborns.
HPLC;MS/MS
Patients
with PKU generally demonstrate an _____ in phenylalanine concentrations
and a ______ in tyrosine concentrations.
increase;decrease
This
inborn metabolic disorder of tyrosine catabolism is characterized by the
excretion of tyrosine and its catabolites in urine or tyrosinuria.
Tyrosinemia
the most severe form occurring in about 1 in 100,000
births worldwide. This form of tyrosinemia is caused by a mutation in the FAH
gene, which codes for the enzyme fumarylacetoacetate hydrolase (FAH).
Type I tyrosinemia
caused by a mutation in the TAT gene, which leads to a
deficiency of the enzyme tyrosine aminotransferase (TAT).
Type II tyrosinemia
rare disorder with only a few cases having been
reported worldwide. It is caused by a mutation in the HPD gene that results in
deficiency of the enzyme 4-hydroxyphenylpyruvate dioxygenase (HPD).
Type III tyrosinemia
is a toxic metabolite that forms when tyrosine cannot be
metabolized through the appropriate enzymatic pathway.
Succinylacetone
The treatment for tyrosinemia is generally a low-protein
diet, but may also include medications such as
nitisinone (NTBC).
A mutation in the HGD
gene leads to a deficiency of the enzyme homogentisate oxidase (HGD), which
is required for proper metabolism of tyrosine and phenylalanine.
Alkaptonuria
HGA is
deposited in the cartilage of the ears, nose, and tendons of the extremities and
results in a dark blue-black pigmentation known as
ochronosis.
may be performed as a rapid screen for the presence
of HGA in urine.
ferric chloride test
Patients with alkaptonuria may be prescribed high-dose
Vitamin C
results from an absence or greatly reduced
activity of a complex of enzymes known as branched-chain α-ketoacid
decarboxylase (BCKD).
Maple syrup urine disease (MSUD)
modified Guthrie test (MSUD): An agar gel plate
containing _______, another growth inhibitor, is inoculated with Bacillus
subtilis.
4-azaleucine,
A leucine concentration greater than ____ is indicative of MSUD.
4 mg/dl
is an autosomal recessive disorder caused by mutation
of the IVD gene, which codes for isovaleryl-CoA dehydrogenase
Isovaleric acidemia (IVA)
Mutations in the CBS, MTHFR, MTR, MTRR, and MMADHC
can result in
homocystinuria.
This mutation results in a deficiency of the enzyme ______, which is necessary for metabolism of methionine.
cystathionine β-
synthase
Treatment includes dietary restriction of proteins to reduce concentrations of
methionine as well as high doses of
Vitamin B6
modified Guthrie test (Homocystinuria): In this form of the test, _________ is
utilized as the bacterial growth inhibitor and increased plasma methionine levels
will result in bacterial growth.
L-methionine sulfoximine
Citrullinemia belongs to a class of genetic diseases called
urea cycle disorders.
is the result of a mutation in the ASS1 gene. This gene
codes for synthesis of the enzyme argininosuccinic acid synthetase (ASS).
Type I citrullinemia
caused by a mutation in the SLC25A13 gene that
codes for production of the transport protein citrin.
Type II citrullinemia
helps transport
molecules inside the cell that are used in the production and breakdown of
simple sugars, production of proteins, and the urea cycle.
Citrin
another urea cycle amino acid disorder that
is inherited in an autosomal recessive pattern and is the result of a mutation in
the ASL gene.
Argininosuccinic aciduria (ASA)
is an inherited autosomal recessive disorder, occurring in
approximately 1 in 10,000 births worldwide, which is caused by mutations in the
SLC3A1 and SLC7A9 genes.
Cystinuria
characterized by inadequate reabsorption of cystine
during urine formation in the kidneys resulting in an elevated concentration of
cystine.
Cystinuria
forms a more soluble
complex with cystine, which prevents it from precipitating and forming stones.
Penicillamine
Cystinuria can be diagnosed by testing the urine for cystine using _______, which produces a red-purple color on reaction with sulfhydryl
groups.
cyanide
nitroprusside
Patients with cystinuria also excrete elevated concentrations of
lysine, arginine, ornithine
Blood samples for amino acid analysis should be drawn after at least _____hrs
of fasting to avoid the effect of absorbed amino acids originating from dietary
proteins.
6-8
For amino acid screening, the method of choice is
thin-layer
chromatography.
It is the fact that proteins contain ______ that sets them apart from pure
carbohydrates and lipids,
nitrogen
four distinct levels of a protein’s structure:
primary, secondary,
tertiary, and quaternary.
represents the number and types of
amino acids in the specific amino acid sequence.
Primary structure
refers to commonly formed structures stabilized by
hydrogen bonds between the amino acids within the protein.
Secondary structure
refers to the overall shape, or conformation, of the protein
molecule.
Tertiary structure
is the shape or structure that results from the
interaction of more than one protein molecule, or protein subunits, held together
by noncovalent forces such as hydrogen bonds and electrostatic interactions.
Quaternary structure
lysine, arginine, and histidine
basic groups
glutamate,
aspartic acid, cysteine, and tyrosine.
acidic groups
The pH at which an amino
acid or protein has no net charge is known as its:
isoelectric point (pI).
Proteins differ in their pI values, but for most proteins it occurs in the
pH range of
5.5-8
The solubility of proteins in blood requires a pH in the
range of
7.35 to 7.45.
When the secondary, tertiary, or quaternary structure of a protein is
disturbed, the protein may lose its functional and chemical characteristics. This
loss of its native, or naturally occurring, folded structure is called:
denaturation.
TRUE/FALSE: Protein synthesis occurs at a rate of approximately two to six peptide bonds
per second.
TRUE
The breakdown of protein occurs in the digestive tract and kidneys, but
primarily in the
liver.
There are two main routes for converting intracellular proteins to
free amino acids:
lysosomal pathway and a cytosolic pathway.
The central reactions that remove amino acid nitrogen from the body are
known as
transaminations.
proteins that catalyze biochemical reactions. They are normally
found intracellularly, but are released into the bloodstream as a result of tissue
damage,
Enzymes
chemical messenger proteins that control the action(s) of specific
cells or organs.
Hormones
serve as reservoirs for metal ions and amino acids so they can
be stored without causing harm and released later.
Storage proteins
contain peptide chains composed of only amino acids.
Simple proteins
globe-like and have
symmetrical proteins that are soluble in water.
Globular proteins
form long protein filaments or subunits, are asymmetrical and usually
inert, and are generally water insoluble due to their hydrophobic R groups.
Fibrous
proteins
consist of a protein and a nonprotein.
Conjugated proteins
The nonamino part
of a conjugated protein is generally referred to as the
prosthetic group.
have a metal ion attached to
the protein,
Metalloproteins
When the percentage of carbohydrate is greater than 40%, the
protein conjugate is referred to as a
mucoprotein or proteoglycan.
molecules with a composition of 10% to 40% carbohydrate are
referred to as
glycoproteins.
are those proteins that are combined with
nucleic acids.
Nucleoproteins
transport protein for the thyroid hormones, thyroxine (T4
), and triiodothyronine (T3); also forms a complex with retinol-binding
protein to transport retinol (vitamin A) and is rich in the amino acid tryptophan.
Prealbumin, or transthyretin
Prealbumin has
a half-life of approximately
2 days
synthesized in the liver at a rate of 9 to 12 g/day and is the most
abundant protein in the plasma.
Albumin
Albumin leaves the bloodstream at a rate of 4% to 5% of
the total intravascular albumin concentration per hour. This rate of movement is
known as the
transcapillary escape rate
half-life of serum
albumin is
20 days
Mutations resulting from an autosomal recessive trait can cause an absence of
albumin, known as
analbuminemia
presence of albumin that has unusual
molecular characteristics; demonstrated by the presence of two albumin bands during
electrophoresis instead of the single band usually observed.
bisalbuminemia.
Its main function
is in the inhibition of the protease, neutrophil elastase.
α1
-Antitrypsin
Several phenotypes of α1
-antitrypsin deficiency have been
identified. The most common phenotype is ____ and is associated
with normal α1
-antitrypsin activity.
MM (allele PiM)
is at greatest risk for developing
hepatic and pulmonary disease from α1
-antitrypsin deficiency.
homozygous phenotype ZZ
spina bifida, neural tube defects, abdominal wall defects,
anencephaly, general fetal distress, and the presence of twins.
elevated AFP
concentration
AFP screening is performed between _______ weeks gestation when
maternal AFP increases
15 and 20
is a reflection of an individual patient’s value compared with the
median.
multiple of the median or MoM
AFP may also be used as a tumor marker and is fractionated by affinity
electrophoresis into three isoforms:
(L1, L2, and L3)
The isoforms are based on their reactivity
with the lectin
Lens culinaris agglutinin (LCA).
considered as a tumor marker for the North American population for screening
chronic liver disease patients for hepatocellular carcinoma (HCC).
AFP-L3
major plasma glycoprotein
that is negatively charged even in acidic solutions lending to its name.
α1
-Acid glycoprotein (AAG), or orosomucoid
also used in diagnosis and evaluation of neonatal bacterial infections.
α1
-Acid glycoprotein (AAG), or orosomucoid
α-globulin glycoprotein that is a member of the serine proteinase inhibitor (serpin) family.
α1
-Antichymotrypsin
is also associated with the pathogenesis of
Alzheimer’s disease as it is an integral component of the amyloid deposits in
Alzheimer’s disease.
α1
-Antichymotrypsin
family of serine protease inhibitors,
assembled from two precursor proteins: a light chain and one or two heavy
chains.
Inter-α-trypsin inhibitors (ITIs)
also known as group-specific component or vitamin D–
binding protein.
Gc-globulin (Gc)
may be of importance for
bone formation and in the immune system as it can act as a cochemotactic factor
in facilitating chemotaxis of neutrophils and monocytes.
Gc-globulin (Gc)
three major electrophoretic variants of Gc exist
Gc2, Gc1s, and Gc1f.
the method of choice for Gc measurements in the clinical laboratory.
Immunonephelometry
TRUE/FALSE: An individual’s haptoglobin phenotype has been reported as an independent
risk factor for cardiovascular disease (CVD) in patients with type 2 diabetes
mellitus.
TRUE
bind free
hemoglobin to prevent the loss of its constituent, iron, into the urine.
haptoglobin
Three phenotypes of haptoglobin are found in humans:
Hp1-1, Hp2-
1, and Hp2-2.
is an autosomal recessive
inherited disorder associated with decreased concentrations of ceruloplasmin,
typically 0.1 g/L, and excess storage of copper in the liver, brain, and other
organs, which results in hepatic cirrhosis and neurologic damage.
Wilson’s
disease
Copper is also deposited in the cornea,
producing the characteristic:
Kayser-Fleischer rings.
inhibits proteases such as trypsin, thrombin, kallikrein, and
plasmin by means of a bait region that can entrap proteinases.
α2
-Macroglobulin
It is the major component of the β-globulin fraction on protein
electrophoresis and plays an important role in the transport of iron.
Transferrin, or siderophilin
is inherited as an autosomal recessive trait due to mutation
of both transferrin genes, with a resulting absence of transferrin.
Atransferrinemia
bind with free heme, which causes oxidative
damage.
Hemopexin
the light chain component of the major
histocompatibility complex or human leukocyte antigen (HLA). This protein is
found on the surface of most nucleated cells and is present in high
concentrations on lymphocytes.
β2-Microglobulin
It is synthesized in the
liver and is classified as a glycoprotein because it has considerable carbohydrate
content.
Fibrinogen
TRUE/FALSE: individuals
with CRP levels greater than 3 mg/L have four to six times greater risk for
development of diabetes than individuals with lower levels of CRP.
TRUE
is the C-reactive protein, but is named for a
monoclonal antibody–based test methodology that can detect CRP at levels
below 1 mg/L.
High-sensitivity CRP (hsCRP)
Acute-phase reactants
CRP Ceruloplasmin Hemopexin Haptoglobin α1-Antichymotrypsin α1-Acid glycoprotein (AAG) α1-Antitrypsin Albumin Fibrinogen Transferrin Prealbumin
it is also a useful marker for monitoring the success or
failure of reperfusion.
myoglobin
is a nephrotoxin, and in
severe muscle injury, concentrations of myoglobin may raise very quickly
causing damage to the kidneys.
myoglobin
Cardiac troponin (cTn) represents a complex of regulatory proteins that include:
troponin C (TnC), troponin I (cTnI), and troponin T (cTnT)
are considered the “gold standard” for
diagnosis of acute coronary syndrome (ACS) in which the blood supply to the
heart muscle is suddenly impeded.
Cardiac troponins
Natriuretic peptides are a family of structurally related hormones that include:
atrial natriuretic peptide (ANP), B-type (or brain) natriuretic peptide (BNP), C-
type natriuretic peptide (CNP), and dendroaspis natriuretic peptide (DNP).
NT-proBNP and BNP are found in greatest
concentration in the
left ventricular myocardium
is used to help predict the short-term risk of
premature delivery.
Fetal fibronectin (fFN)
an accurate marker of cerebrospinal fluid
leakage and have also been used as a potential marker in detecting impaired
renal function
β-Trace protein (BTP), or prostaglandin D synthase
not
influenced by glucocorticoid therapy; evaluated as a promising
marker in the diagnosis of perilymphatic fluid fistulas.
β-Trace protein (BTP)
proteolytic fragments of collagen I
formed during bone turnover, and their presence in serum and urine is a
biochemical marker of bone resorption.
Cross-linked C-telopeptides (CTXs)
is used to measure CTX in the laboratory.
ECLIA technology
is freely filtered by the glomerulus and almost completely
reabsorbed and catabolized by the proximal tubular cells; new sensitive endogenous serum marker for the
glomerular filtration rate because it is produced and destroyed at a fairly constant
rate.
Cystatin C
insoluble fibrous protein aggregates formed due to an alteration in
their secondary structure known as β-pleated sheets.
Amyloids
refers to
conditions in which amyloids are abnormally deposited in organs and tissues,
including the heart and blood vessels, brain and peripheral nerves, kidneys, liver,
spleen, and intestines, causing localized or widespread organ failure.
Amyloidosis
are not routinely performed, but
may be used to aid in the differential diagnosis of Alzheimer’s disease from other
forms of dementia.
Amyloid β42 (Aβ42) and Tau protein tests
a brain phosphoprotein, make up
part of the structure of neurofibrillary tangles (twisted protein fragments that
clog nerve cells),
Abnormal forms of Tau
formed from β amyloid precursor
protein, is associated with the creation of senile plaques.
Aβ42
The most common method for total nitrogen analysis uses
chemiluminescence
In this method (kjeldahl), proteins are assumed to contain an average mass of \_\_\_\_ nitrogen
16%
measures the amount of nitrogen in the specimen.
Kjeldahl method
widely used method for the determination of
total protein and is recommended by the International Federation of Clinical
Chemistry expert panel.
biuret procedure
The reagent also contains ______, which forms a
complex with cupric ions to prevent their precipitation in the alkaline solution,
and ______, which acts as an antioxidant.
sodium potassium tartrate; potassium iodide
Globulins may be elevated due to
conditions such as:
multiple myeloma, chronic inflammatory disorders, and
rheumatoid arthritis.
globulins are separated from albumin by a precipitation
process using sodium salt.
Salt Fractionation
is not specific for albumin and β- lipoproteins and some α1 - and α2 -globulins will bind to this dye, which could result in falsely elevated values.
Methyl orange
is more specific for albumin, but several
compounds, such as salicylates (aspirin), penicillin, conjugated bilirubin, and
sulfonamides interfere
hydroxyazobenzene-benzoic acid (HABA)
is not affected by interfering substances such as
bilirubin and salicylates; however, hemoglobin binds
BCG
is not affected by interfering substances such as
bilirubin and salicylates; however, hemoglobin binds & interferes
BCG
The total globulin concentration in serum is determined by a
direct colorimetric method using
glyoxylic acid (results in purple color)
uses a higher
voltage coupled with a cooling system in the electrophoretic apparatus and a
more concentrated buffer.
High-Resolution Protein Electrophoresis
collection of techniques in which the separation of
molecules takes place in silica capillaries.
Capillary Electrophoresis
the
negatively charged molecules in the specimen also have a tendency to migrate
back toward the positively charged injector end; this is referred to as
electrophoretic mobility.
zone electrophoresis that separates proteins on the
basis of their pI.
Isoelectric focusing (IEF)
phenotyping of α1
-antitrypsin
deficiencies, determination of genetic variants of enzymes and hemoglobins,
detection of paraproteins in serum, oligoclonal bands in CSF, and isoenzyme
determinations.
clinical applications of IEF
Low CSF
protein values are found in
hyperthyroidism and when fluid is leaking from the
central nervous system.
other conditions that induce
CNS demyelination and elevated concentrations of myelin basic protein include
meningoencephalitis, SLE, diabetes mellitus, and chronic renal failure.
In very active demyelination, concentrations
of myelin basic proteins of
17 to 100 ng/mL
In slow
demyelination, values of
6 to 16 ng/mL
in remission, the values are
less than
4 ng/mL.
presence of oligoclonal bands are found in:
Multiple sclerosis
Guillain-Barre syndrome, bacterial meningitis, viral encephalitis,
subacute sclerosing panencephalitis, and neurosyphilis.
TP: Normal/Decreased
Albumin: Decreased
Globulin: Increased
Hepatic damage, burns, trauma, infections
TP: Decreased
Albumin: Decreased
Globulin: Normal
Malabsorption, Inadequate diet, Nephrotic syndrome
TP: Decreased
Albumin: Normal
Globulin: Decreased
Immunodeficiency syndromes
TP: Decreased
Albumin: Decreased
Globulin: Decreased
Salt Retention Syndrome
TP: Increased
Albumin: Increased
Globulin: Increased
Dehydration
TP: Increased
Albumin: Normal
Globulin: Increased
Multiple myeloma, monoclonal & polyclonal gammopathies
