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u Large molecules referred to as: ________________________________

n Fundamental building blovk of protein: _____________________________
u Protein soluble in water: _________________________
u Element that distinguishes protein from CHO and lipids is ___________________
n Catabolism and Nitrogen balance:
² Anabolism: _____________
² Catabolism: ____________
n __________________________: happens when more nitrogen is incorporated in the bodu than excreted
² Ex: Pregnant women, growing children and adults recovering from major illness
n __________________________: happens when more nitrogen is excreted than is incorporated into the body
² Ex: Burns, wasting diseases, continual high fever and starvation
n Two main routes for converting intracellular proteins to free amino acids:
² Lysosomal pathway- degrades extracellular proteins
² Cytosolic pathway- degrades important intracellular proteins
n Central reaction that remove amino acid nitrogen from the body or removal of nitrogen from free amino acids:
_____________________________
n Form of amino acid with 2 differing charges and with a net charge of zero: ______________
n The pH value at which the sum of a molecule’s charges equals zero is called: ____________________
² When pH > pI --> protein charge is _____________
² When pH < pI --> protein charge is _____________
² pI = point at which the number of positive charged group equals the number of negatively charged group in a
protein

Functions of Proteins
1. Repair body tissues (ex. Fibrinogen-related proteins)
2. Important in blood coagulation and immunologic function (ex. Hemostasis and Antibodies)
3. For transport of metabolic substance (ex: Insulin- regulates blood pressure)
4. Maintenance of osmotic pressure (ex. Albumin)
5. Maintenance of blood pH (buffers)
6. Biocatalysts (ex. Enzymes – expedite the rate of chemical reactions by reducing the activation energy)

PROTEIN STRUCTURE AND FUNCTIONS:

Functions:
ü Shape dictates its functions
ü Shape is dictated by sequences (tranlation)
ü Changes in the sequence changes the shape
ü Change in shape changes its function
STRUCTURE ASPECT BOND TYPE
PRIMARY ü Amino acids arranged in specific sequence unique for
that person Formed when carboxyl group of one
ü Determines the identity of a protein, what its amino acid joins to the amino group of a
molecular structure is, what functions can it perform, second forming a molecule water as a
how it can bind to other molecules, and how it can byproduct
participate in the recognition between molecules and
cells
ü linear sequence of the amino acid in a protein
SECONDARY ü Twisted shape of primary structure due to rotation of
bonds (regularly repeating structures stabilized by
hydrogen bonds)
ü Involves the winding of the polypeptide chain
ü Refers to commonly formed structures stabilized
by hydrogen bonds between the amino acids within
the protein.
ü Shape may be a-helix (most common globular
protein shape), pleated sheet or random coil
TERTIARY ü Refers to the overall shape, or conformation, of the Relatively weak interactions of amino
protein molecule. The conformation is known as the acid R groups which include disulfide
fold, or the spatial relationship of the secondary linkages and noncovalent attraction like
structures to one another. hydrogen bonds, electrostatic,
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ü Three dimensional (3D) structure that forms when hydrophobic and Vander Waals forces
the amino acid chains folds back on itself
ü Maintained by electrovalent linkages, hydrogen
bonds, disulfide bridges, Van der waals forces and
hydrophobic interactions
ü Responsible for many of the physical and chemical
properties of the proteins
QUATERNARY ü Interaction or combination of more than one protein Non-covalent attraction same with
molecule or subunits tertiary

Term used to describe the loss of the native or naturally occuring folded structure of proteins: __________________________
Proteins are affected by denaturation by: _______________________________________
Methods for Denaturation:
1. Mechanical/agitation
2. Heat = Urine + SSA
3. Chemical = use of heavy metal (Tungstic acid)/organic solvent (Acetone)
a) Strong acids:
i. SSA = for CSF protein through TURBIDIMETRIC METHOD (Dye: Coomasie dye)
ii. TCA
ENZYMES FOR DIGESTION OF PROTEINS:
1. PEPSIN =stomach enzyme that serves to digest proteins found in ingested foods
= Pepsinogen: inactive zymogen, secreted by the GASTRIC CHIEF CELLS
= Parietal cells within the stomach lining secrete HYDROCHLORIC ACID that lowers the pH of the stomach
2. TRYPSIN = a proteolytic enzyme or proteinase that helps break down proteins
= produced in the pancreas
3. CHYMOTRYPSIN = break down proteins into individual amino acids
= specifically targets the amino acids, tyrosine, phenylalanine, and tryptophan
4. ELASTASE = helps breakdown fats, carbohydrates, proteins
= primary role: breaks down elastin , a protein that imparts elasticity to connective tissue
PANCREATIC ELASTASE 1: reflects overall pancreatic exocrine function
5. CARBOXYPEPTIDASE A= a protease enzyme that hydrolyzes/cleaves a peptide bond at the carboxy-terminal end of a
protein
or peptide
= Requirement for its activity: _______________________

CLASSIFICATION ACCORDING TO STRUCTURE

Simple u COMPOSDE OF AMINO ACIDS LINKED BY A PEPTIDE BONDS
u Fibrous = provide structure to cells, such as connective tissues, tendons,bone, and muscle
Examples: fibrinogen, troponins, collagen
u Globular = globe-like and have symmetrical proteins that are soluble in water;
compact and have little or no space for water in the interior of the molecule; function
astransporters, enzymes, and messengers
Examples: albumin, hemoglobin, and the immunoglobulins, IgG, IgA, and IgM

Conjugated u CONSIST OF A PROSTHETIC GROUP (nonamino part of a conjugated protein) AND

PROTEIN
ü Metalloprotein = have a metal ion attached to the protein, either directly; storage and
transport of proteins, enzymes, and signal transduction proteins, or infectious diseases
*Metal ions attached: Ferritin (iron), ceruloplasmin (copper)
*Complex metal: hemoglobin and flavoproteins
ü Lipoproteins: Lipids attached - HDL, LDL, VLDL
ü Mucoproteins: aka PROTEOGLYCANS; building blocks of mucous; contains >40% of CHO-
Mucin (lubricant that protects the body surface from friction or erosion)
ü Glycoproteins: functions includes immunity and cell adhesion; contains 10-40% CHO -
haptoglobin and a1-antitrypsin
ü Nucleoproteins: conjugated protein containing nucleic acids (RNA or DNA) - chromatin
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PLASMA PROTEINS

PLASMA PROTEIN COMMENTS INCREASED DECREASED

Prealbumin ü Indicator of nutrition u Steroid therapy ² Liver disorders
ü Binds thyroid hormones u Chronic renal failure ² Inflammation
(T3, T4) u Alcoholism ² Malignancy
ü Binds retinol-binding ² Poor nutrition
protein
Albumin ü Binds bilirubin, steroids u Dehydration ² Liver disorders
and fatty acids (decreased synthesis)
ü Major contributor to ² GIT associated
oncotic pressure ² Malabsorption
ü Reservoir of amino acids ² Muscle wasting disease
ü Analbuminemia: ______ ² Severe burns
ü Bisalbuminemia: ______ ² Renal disease (Nephrotic
syndrome,
Normal value: 3.5-5.0 g/dL Glomerulonephritis)
² Starvation
² Malnutrition
(KWASHIORKOR &
MARASMUS)
ALPHA 1 GLOBULINS COMMENTS INCREASED DECREASED
α1- Antitrypsin ü Acute phase reactant u Inflammatory response ² Hereditary defect,
ü Protease inhibitor (Acute inflam response Deficiency is assoc w/
(highest concentration is the most sensitive increased destruction of
in the plasma) indicator) lungs due to TRYPSIN
ü Inactive trypsin and u Estrogen (Contraceptive
other proteolytic use) and Androgen
enzymes therapy

Normal value: 200-400 mg/dL

α1- Fetoprotein ü Principal fetal protein u Neural tube defects ² Trisomy 21 & Trisomy 18
u Spina bifida
u Fetal distress
u Anencephaly
α1- Acid Glycoprotein ü Aka Orosomucoid u Nephrotic syndrome, ² RA, pneumonia,
ü Major plasma stress, inflammation, conditions associated
glycoprotein in the α1 tissue damage, AMI, with cell proliferation
trauma, pregnancy,
Normal value: 50-120 mg/dL cancer, pneumonia, RA,
and surgery
α1- Lipoprotein ü Transports lipids (HDL) u NONE ² NONE
α1- Antichymotrypsin ü Inhibits serine proteases u Inflammation ² Liver disease
Inter-α- trypsin inhibitor ü Inhibits serine proteases u Inflammation ² NONE
Gc-globulin ü Transports vitamin D and u 3RD trimester of ² Liver disease, Protein-
bind actin pregnancy losing sydromes
ü May act as chemotactic u Intake of estrogen oral
factor in facilitating contraceptives
chemotaxis of neutrophil
and monocytes during
inflammation
Method of choice:
IMMUNONEPHELOMETRY

Normal value: 20-55 mg/dL

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ALPHA 2 GLOBULINS COMMENTS INCREASED DECREASED
Haptoglobin ü Acute phase reactant u stressful conditions, ² intravascular hemolysis
- binds Hgb myoglobulinuria, and hemoglobinuria
- useful marker for ulcerative colitis, acute ² Liver disase, low RBC
hemolysis (decreased) & rheumatic disease, production
hemoglobinuria acute myocardial
infarction, and severe
Normal value: 100-300 mg/dL infections, burns and
nephrotic syndrome
Ceruloplasmin ü Acute phase reactant u Malnutrition, ² Pregnancy,
ü Copper-carrying protein malabsorption, severe inflammatory disorders,
(65-90%) liver damage malignancies, intake of
oral estrogen and
Normal value: 18-45 mg/dL contraceptives
α2- Macroglobulin ü Is the largest major u Acute inflammatory ² DIC
nonimmunoglobulin disorders, prostatic ² Peptic ulcer disease
protein in plasma. cancer, acute
(800,000 kb) pancreatitis
ü The spectrum of u Nephrotic syndrome -
inhibition by AMG is very increases 10x (renal and
wide (inhibits proteases, GI disorders)
serines, carboxyl, thiol) u liver disease and DM,
contraceptive use,
Normal Values: pregnancy, estrogen
150-350 mg/dL (male) therapy
175-420 mg/dL (female)
BETA GLOBULINS COMMENTS INCREASED DECREASED
Beta-2 Microglobulin ü is a light chain u renal failure, multiple ²
component of the major myeloma, rheumatoid
human leukocyte antigen athritis (RA), systemic
(HLA) lupus erythematosus
ü it is found on the surface (SLE), and HIV
of most nucleated cells;
present in high
concentration on
lymphocytes
ü it is needed in the
production of CD8 cells
ü common cause of
dialysis-associated
amyloidosis

Normal value: 0.2-2.8 ug/dL

Transferrin ü A glycoprotein and it is a u IDA, Estrogen use ² Infections, liver disease,
major component of the nephrotic syndrome
β2- globulin fraction
ü Negative acute phase
reactant
ü Synthesized by the liver

Normal value: 200-400 mg/dL

Complement (C4, C3, C1q) ü Enhance immune u Inflammation, biliary ² Liver or kidney disease,
response obstruction post-surgery or infection

Normal value: 80-160 mg/dL

Fibrinogen ü Precursor of fibrin clot, u Inflammation, ² Coagulation
elevate with other acute pregnancy, use of oral
phase reactants contraceptives
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Hemopexin ü Synthesized by the liver u Inflammation, DM, ² Diagnostic of hemolytic
ü A small beta globulin Duchenne Type anemia
that binds to free Heme Muscular dystrophy,
(protoporphyrin IX) some malignancies
(melanomas)
GAMMA GLOBULINS COMMENTS INCREASED DECREASED
G,A,M,D,E ü u ²
C-Reactive protein ü Acute phase reactant, u Tissue necrosis, RF, ²
motivates phagocytosis infections, AMI, RA, gout
in inflammation
OTHER PROTEINS COMMENTS INCREASED DECREASED
β2- Microglobulin ü Single polypeptide chain u SLE, Renal failure, ²
that is the light chain lymphocytosis
component of HLA found
in the surface of
nucleated cells and
present in lymphocytes
Fibronectin ü A glycoprotein u Fibronectin ²
ü Nutritional marker glomerulonephritis
ü Roles: Cell adhesion,
tissue differentiation,
growth and wound
healing
Cross-linked C-telopeptides ü Considered a u ²
biochemical marker of
bone resorption in urine
and serum
ü Most useful in
monitoring response to
antiresorptive therapy
Β-trace protein ü Accurate marker of CSF u ²
leakage
ü Potential marker of
impaired renal function
Cystatin C ü New marker for changes u ²
in GFR
ü Used for screening and
monitoring of kidney
dysfunction
Amyloid ü Amyloid vs Tau protein u ²
(used to differentiate
Amyloidosis and
Alzheimer’s disease)
ü Low Amyloid and High
Tau protein- suggestive
of: __________________
ü Abnormal amyloid and
Tau= ________________
Myoglobin ü Primary oxygen carrying l Progressive muscular dystrophy, Crushing injury (skeletal
protein found in striated muscle disorder), Renal failure, AMI, Angina w/o
skeletal and cardiac infarction, Rhabdomyolysis
muscke l Myopathies, Vigorous exercise, IM injections, open heart
ü Reversible binds to surgery, seizure (tonic-clonic), electric shock, arterial
oxygen like hemoglobin thrombosis
l Certain toxins
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TOTAL ALBUMIN GLOBULIN DISEASE

PROTEIN
Dehydration
Immunodeficiency syndrome
Salt retention syndrome
Hepatic damage, Cirrhosis, Beta-gamma bridging, Hepatitis, Increase gamma
globulins, Obstructive jaundice (increase alpha2), burns, trauma, infections
Malabsorption, inadequate diet, Nephrotic syndrome, increase alpha-2 and beta
globulins, decrease gamma globulins

Reference urine albumin value: __________________

Multiple myeloma, polyclonal gammopathies

GENERAL CLINICAL SIGNIFICANCE

CAUSES OF INCREASED VALUES CAUSES OF DECREASED VALUES
TOTAL PROTEIN Dehydration, severe exercise, infections, Gastrointestinal cancers, liver damage,
cancer malnutrition, low thiamine,
glomerulonephritis
ALBUMIN Dehydration, sunstroke, exercise, Pregnancy, malnutrition, malabsorption,
multiple sclerosis, hypothyroidism liver disease, kidney disease, burns

ELECTROPHORESIS PATTERN
MULTIPLE MYELOMA= Monoclonal (destruction band, HYPOALBUMINEMIA= Low spike for albumin
hypercalcemic bone), Hyperglobulinemia
CHRONIC LIVER DISEASE= diffuse but large elevation of CHRONIC INFLAMMATORY DISEASE= diffues but small
gamma globulin elevation of gamma globulin
DYSPROTEINEMIA (MONOCLONAL GAMMOPATHY)= sharply HYPOGAMMAGLOBULINEMIA= flat curve where gamma
elevated spike in gamma globulin globulin should be
NEPHROTIC SYNDROME= low albumin spike, very high beta PROTEIN-LOSING ENTEROPATHY= low albumin spike,
globulin moderate alpha-2 globulin elevation
ALPHA-1 ANTITRYPSIN DEFICIENCY= flat curve where alpha-1 PROTEIN-LOSING ENTEROPATHY SEEN IN MALABSORPTION
globulin should be SYNDROME= low albumin and gamma globulin; high alpha-2
globulin
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