C - Chapter VII: Proteins Flashcards
PROTEINS
-covalently linked polymers of (?)
amino acids
PROTEINS
- amino acids are linked via (?) (formed upon removal of a water molecule)
peptide bond
PROTEINS
- synthesized in the liver & secreted by the hepatocyte into the circulation EXCEPT (?)
immunoglobulins (plasma cells)
PROTEIN
- provide (?) of the total daily body energy requirement
12 – 20%
PROTEINS
- composes (?) of the cell’s dry weight
50 – 70%
- amphoteric
PROTEINS
sequence of the amino acids in the polypeptide chain
Primary structure
analytical processes:
chromatography, electrophoresis, dye binding and light absorbance depend on this sequence
arises from the interaction among the different segments of a polypeptide chain
Secondary structure
– chain forms a regular helix ; coil resembling a spring
a. alpha-helix
– in fully extended structures; flat, corrugated structure
b. beta-pleated sheets
– no apparent pattern
c. random coils
– actual 3-dimensional structure or folding pattern of the protein
- Tertiary structure
– association of several polypeptide chains into larger “oligomeric” aggregate unit
- Quaternary structure
stable complexes:
dimers, trimers, tetramers
Classification
- Simple
- Conjugated
contain peptide chains that on hydrolysis yield only AA
- Simple
protein (apoprotein) + nonprotein (prosthetic group)
- Conjugated
prosthetic group :
lipid (lipoprotein) , carbohydrate (glycoprotein) , metals (metalloprotein) , etc.
: relatively symmetrical with compactly folded and coiled polypeptide chains
a. globular
: more elongated and asymmetrical and have a higher viscosity
b. fibrous
Functions
- Repair (?)
- Important in (?)
- For transport of (?)
- Maintenance of (?)
- Maintenance of (?) (buffers)
- Bio-(?)
body tissues
blood coagulation and immunologic function
metabolic substances
osmotic pressure
blood pH
-catalysts
Metabolism
- Dietary Intake
- Absorption
- Production
- Storage
- Destruction
MAJOR PLASMA PROTEINS
- PRE-ALBUMIN (Transthyretin)
- ALBUMIN
- GLOBULINS
− Migrates ahead of albumin
− Rich in tryptophan and contain 0.5% carbohydrate
PRE-ALBUMIN (Transthyretin)
− Serves as transport protein for T3, T4 and retinol (Vit. A)
PRE-ALBUMIN (Transthyretin)
− Increased: alcoholism, chronic renal failure, steroid treatment
PRE-ALBUMIN (Transthyretin)
− Decreased: poor nutrition, liver disorder, malignancy
PRE-ALBUMIN (Transthyretin)
− largest plasma protein fraction (52-62%)
ALBUMIN
− synthesized in the liver at a rate that is dependent on protein intake
ALBUMIN
− serves as circulating reservoir of amino acids
ALBUMIN
− regulator of osmotic pressure
ALBUMIN
− transport protein because of ease of binding with blood components
ALBUMIN
− a “negative acute phase reactant”
ALBUMIN
− sensitive & highly prognostic marker in cases of cystic fibrosis
ALBUMIN
ALBUMIN
Reference values:
3.5 – 5.0 g/dL (35 – 50 g/L)
Increased − hemoconcentration, dehydration
ALBUMIN
Increased
− excessive infusion
albumin (Hyperalbuminemia)
− decreased synthesis (liver impairment)
Decreased albumin (Hypoalbuminemia)
− malabsorption or malnutrition
Decreased albumin (Hypoalbuminemia)
Decreased − nephrotic syndrome (renal loss)
albumin (Hypoalbuminemia)
Decreased − severe burns
albumin (Hypoalbuminemia)
– heterogenous complex mixture of protein molecules (α1, α2, β and γ fractions)
GLOBULINS
Elevated concentration of globulin in early cirrhosis will balance loss of albumin resulting to normal levels of total protein
GLOBULINS
GLOBULINS
normal A/G ratio :
1.3 – 3 : 1
GLOBULINS
low A/G ratio
– liver diseases, infectious diseases, multiple myeloma, nephritis
Alpha1-globulins
a. α-1-antitrypsin
b. α-1-fetoprotein
c. α-1-Acid Glycoprotein (orosomucoid)
d. α-1-Antichromotrypsin
Alpha2-globulins
A. Haptoglobin
B. Ceruloplasmin
Beta-globulins
a. Transferrin (Siderophilin)
b. β2-Microglobulin
GLOBULINS
(1) Alpha1-globulins
(2) Alpha2-globulins
(3) Beta-globulins
(4) GAMMA-GLOBULINS
(5) FIBRINOGEN
(6) LIPOPROTEIN
(7) COMPLEMENT
(8) C-REACTIVE PROTEIN
– 90% of the α1-globulin band
α-1-antitrypsin
- an acute phase reactant
α-1-antitrypsin
- neutralize trypsin-like enzymes
α-1-antitrypsin
- major inhibitor of protease activity
α-1-antitrypsin
inhibit lysosomal elastase released from PMNs during their
α-1-antitrypsin
- Increased: inflammation, pregnancy and contraceptive use
α-1-antitrypsin
- Decrease: associated with emphysematous pulmonary disease & juvenile hepatic cirrhosis
a. α-1-antitrypsin
b. α-1-fetoprotein
c. α-1-Acid Glycoprotein
α-1-antitrypsin
synthesized initially by the fetal yolk sac & then the parenchymal cells of the liver
- used as a tumor marker (hepatic & gonadal CA)
a-1-fetoprotein
- screening test for any fetal conditions, increase passage of fetal proteins into the amniotic fluid; detects neural tube defects
a-1-fetoprotein
- Increased: neural tube defects (spina bifida), atresia of the GIT, fetal distress, ataxia telangiectasia, tyrosinosis, hemolytic disease of the newborn (HDN)
α-1-fetoprotein
- Decreased: Down’s syndrome
α-1-fetoprotein
- contains high percentage of CHO and sialic acid (45% CHO + 11-12% Sialic acid)
α-1-Acid Glycoprotein (orosomucoid)
- synthesized both by the liver & by granulocytes and monocytes
α-1-Acid Glycoprotein (orosomucoid)
- inhibits the phagocytic activity of neutrophils & inhibits platelet aggregation
α-1-Acid Glycoprotein (orosomucoid)
- may inactivate progesterone
α-1-Acid Glycoprotein (orosomucoid)
Increased: pregnancy, cancer, pneumonia, rheumatoid arthritis (RA), cell proliferation
α-1-Acid Glycoprotein (orosomucoid)
Decreased: nephrotic syndrome
α-1-Acid Glycoprotein (orosomucoid)
Alpha1-globulins
a. α-1-antitrypsin
b. α-1-fetoprotein
c. α-1-Acid Glycoprotein (orosomucoid)
d. α-1-Antichromotrypsin
an acute phase reactant
α-1-antitrypsin
Haptoglobin
FIBRINOGEN
- synthesized in the hepatocytes & cells of the RES
Haptoglobin
- binds free hemoglobin by its α- chain
Haptoglobin
- one of the proteins used to evaluate rheumatic diseases
Haptoglobin
Increased: inflammation, nephrotic syndrome, burns, trauma
Haptoglobin
Decreased: intravascular hemolysis and liver disease
Haptoglobin
copper-containing protein BUT does NOT transport copper
Ceruloplasmin
synthesized in the liver, where 6-8 copper atoms are attached
Ceruloplasmin
- serves as an antioxidant to prevent lipid peroxidation & cellular damage
Ceruloplasmin
- increased in inflammation and pregnancy
Ceruloplasmin
- indicator for Wilson’s disease (0.1 g/L)
Ceruloplasmin
Ceruloplasmin
- Decreased: Wilson’s disease, malnutrition, malabsorption, nephrotic disease, Menke’s disease (kinky hair syndrome)
Wilson’s disease, malnutrition, malabsorption, nephrotic disease, Menke’s disease (kinky hair syndrome)
– largest major non-immunoglobulin protein in plasma
α-2-Macroglobulin
- found principally in the intravascular spaces; does not diffuse from the plasma space
α-2-Macroglobulin
- lower amounts can also be found in CSF
α-2-Macroglobulin
- inhibits proteases such as trypsin, pepsin and plasmin
α-2-Macroglobulin
- major component of the β2-globulin fraction
Transferrin (Siderophilin)
- a glycoprotein synthesized in the liver
Transferrin (Siderophilin)
- transports oxidized iron (Fe+3)to its storage sites
- prevents loss of iron through the kidney
Transferrin (Siderophilin)
Increased: hemochromatosis (bronze skin)
Transferrin (Siderophilin)
Decreased: liver disease, malnutrition, nephrotic syndrome
Transferrin (Siderophilin)
- light chain component of the major human leukocyte antigen (HLA)
β2-Microglobulin
- found on the surface of most nucleated cells
β2-Microglobulin
- present in high concentration on lymphocytes
β2-Microglobulin
- filtered by the renal glomerulus but reabsorbed
β2-Microglobulin
Increased: RA, systemic lupus erythematosus (SLE), HIV
β2-Microglobulin
Increased in:
• chronic inflammation
• cirrhosis or viral hepatitis
• collagen diseases
• paraproteins (monoclonal bands, gammopathies)
GAMMA-GLOBULINS
Decreased in: congenital or acquired immunodeficiency
(4) GAMMA-GLOBULINS
(5) FIBRINOGEN
(7) COMPLEMENT
GAMMA-GLOBULINS
– synthesized in the plasma cells
Immunoglobulins
- not produced to any extent by the neonate
Immunoglobulins
– one of the largest proteins in the blood plasma
FIBRINOGEN
- synthesized in the liver
FIBRINOGEN
- most abundant of the coagulation factors
FIBRINOGEN
- an acute phase reactant; markedly increased during inflammatory process
FIBRINOGEN
- may serve as a marker for long-term prognosis of cardiovascular disease
FIBRINOGEN
- distinct band between β and γ-globulins on electrophoresis
FIBRINOGEN
- it forms a fibrin clot when activated by thrombin
FIBRINOGEN
Increased: pregnancy and use of birth control pills
FIBRINOGEN
FIBRINOGEN Decreased:
Reference values:
extensive coagulation
200 – 400 mg/dL (2.0 -4.0 g/L)
- complexes of proteins & lipids (LDL, HDL, VLDL, Chylomicrons)
LIPOPROTEIN
- transports cholesterol, triglyceride and phospholipids
LIPOPROTEIN
- participates in the immune reaction and serve as a link to the inflammatory response
COMPLEMENT
- circulates as non-functional precursors
COMPLEMENT
Increased: inflammatory states
COMPLEMENT
Decreased: SLE, DIC, malnutrition
COMPLEMENT
- appears in blood of patients with diverse inflammatory diseases
C-REACTIVE PROTEIN
- undetectable in healthy individuals
C-REACTIVE PROTEIN
- precipitates with the C substance, a polysaccharide of pneumococci
C-REACTIVE PROTEIN
- general scavenger molecule; gamma-migrating protein
C-REACTIVE PROTEIN
Increased: acute rheumatic fever, MI, RA, gout, bacterial & viral infections
C-REACTIVE PROTEIN
MISCELLANEOUS PROTEINS:
- Myoglobin
- Troponins
- Amyloid
▪ A heme protein or oxygen-binding transport protein found in skeletal and cardiac muscles
Myoglobin
▪ Approximately 2% of the total muscle protein
Myoglobin
▪ Marker for chest pain (angina) and early detection of acute myocardial infarction (AMI)
Myoglobin
▪ In AMI, the onset is [?], peak level [?], normalize in [?]
1-3 hours
5-12 hours
18-30 hours
▪ Useful marker for monitoring the success or failure of reperfusion
Myoglobin
Increased: AMI, angina, rhabdomyolysis, muscle trauma, extrenuous exercise, IM injection
Myoglobin
▪ A complex of 3 proteins that bind to the thin filaments of striated muscle (cardiac & skeletal)
Troponins
▪ Diagnostic marker for identifying cardiac injury in the presence of a skeletal muscle damage
Troponins
▪ Levels in blood may elevate after AMI in the absence of CK-MB elevations
Troponins
▪ TnT, TnI, TnC = muscle contraction
Troponins
▪ A pathological extracellular deposit associated with a group of disorders collectively called amyloidosis.
Amyloid
Ultimate product of digestion
Amino acids
Enumerate hormones which promote protein synthesis
Growth hormone
Insulin
Thyroid hormone
A type of protein which is formed when the segments of the polypeptide chain interact with one another
Secondary structure
The secondary structure is maintained by this type of bond
Hydrogen bond
A heme containing protein which binds oxygen and skeletal muscles
Myoglobin
Which of the following proteins contains copper and functions as a peroxidase enzyme
Ceruloplasmin
Based on electrophoretic mobility, ceruloplasmin belongs to this type of fraction
Alpha-2-globulin
Among the different classes of proteins, which is a negative acute phase reactant
Albumin
An assay performed on this protein serves as presumptive or differential diagnosis of bacterial and viral infection
C-reactive Protein
This protein is a light chain component the major Human Leukocyte Antigen
Beta-2-microglogulin
Which of the following white blood cells contain a high concentration of beta-2-microglogulin
Lymphocytes
This protein forms a distinct bond between beta and gamma globulins on plasma electrophoresis
Fibrinogen
A decrease of this protein on maternal serum during pregnancy is associated with down’s syndrome
Alpha-1-fetoprotein
Also known as pre-albumin
Transthyretin
Pre-albumin is rich in the amino acid
Tryptophan
The protein that binds with free hemoglobin is
Haptoglobin
Based on electrophoretic mobility, haptoglobin belongs to this type of fraction
Alpha-2-globulin
The deposition of this protein is common among patients with cystic fibrosis
Albumin
In the presence of hemolytic disorders, the plasma level of haptoglobin…
Decreases
Identify the proteins which form complexes with trypsin in the circulation and cause its inactivation
Alpha-1-antitrypsin
Alpha-2-macroglobulin
The largest major non immunoglobulin protein in plasma is
Alpha-2- macroglobulin
An assay of this protein is currently considered the gold standard and laboratory diagnosis of acute myocardial infarction
Troponin
