M1: Specific Proteins II Flashcards
(125 cards)
0
Q
Prealbumin: other name
A
Thyroxine-Binding Pre Albumin (TBPA) or Transthyretin (TTR)
1
Q
Fraction that migrates in a position faster than albumin toward the anode. Tetrametric structure; total MW 62,000 Da; one of the smaller serum proteins.
A
Prealbumin
2
Q
Prealbumin: only a small fraction of thyroxine is bound to
A
TBPA
3
Q
Prealbumin: has a 100 fold greater affinity for thyroxine
A
Thyroxine binding globulin
4
Q
Prealbumin: Significant role in _________ metabolism, by complexing with the RBP.
A
Vit. A
5
Q
Prealbumin: Small protein (182AAs) Rapidly removed from the circulation by filtration through the kidney if it were not held in the plasma by the larger protein prealbumin.
A
Retinol Binding Protein
6
Q
Prealbumin: The complex of RBP and transthyretin appears to be assembled in the _______ of hepatocytes.
A
ER
7
Q
Prealbumin: is rich in
A
Tryptophan
8
Q
Prealbumin: has _________ conformation.
A
B-pleated sheet
9
Q
Prealbumin: portion of prealbumin is the source of the ___________ component in type I Familial Amyloidotic Polyneuropathy.
A
B-fibrillar amyloid
10
Q
Prealbumin: A mutation that produces a protein susceptible to proteolytic cleavage creating B structured fragments that are the building blocks of amyloid in nerve fibers.
A
Type I Familial Amyloidotic Polyneuropathy
11
Q
Prealbumin: has a relatively _____ halflife. (Roughly ___ days)
A
Short. 2.
12
Q
Prealbumin: Synthetic rate is sensitive to intake of adequate _______ and to alterations in _______ function.
A
Nutrition. Hepatic.
13
Q
Prealbumin: Prealbumin secretions in serum ________ in response to alterations in sythetic rate than to those of other proteins.
A
Fluctuate
14
Q
Prealbumin: In hemodialysis patients, low levels of prealbumin were associated with greater risk of ________ & ________ for infection thus, prealbumin measurements can become an important factor for planning patient management.
A
Mortality. Hospitalization.
15
Q
Prealbumin: Electrophoresis of _____ is usually requested for detection of oligoclonal bands of immunoglobulin.
A
CSF
16
Q
Prealbumin: true prealbumin is generally low levels of detection by serum electrophoresis, it is best quantified by immunologic measurements such as _________.
A
Nephelometry
17
Q
Prealbumin: frequently appears in the prealbumin position of serum from patients who have had heparin therapy
A
Protein band
18
Q
Prealbumin: activates and releases lipoprotein lipase activity, which attacks triglycerides in lipoprotein fractions their electrophoretic migration anodally.
A
Heparin
19
Q
Prealbumin: reveals apolipoproteins in the prealbumin position but no _______ fraction. This is an in vivo effect that does not occur if heparin is added to samples already collected.
A
Protein stains. B-lipoprotein functions.
20
Q
The single and most abundant protein in normal plasma usually constituting up to 2/3 of total plasma protein. Depression and losses result in serious imbalance of intravascular oncotic pressure. This loss is manifested clinically by development of _________.
A
Albumin. Peripheral edema.
21
Q
Congenital absence of albumin generally does not lead to such problems, presumably because of lifelong compensatory mechanisms that control hydrostatic pressures.
A
Analbuminemia
22
Q
Also serves as a mobile repository of AAs for incorporation into other proteins. General transport or carrier protein. Many organic & inorganic ligands are complexed with different regions of the albumin molecule in covalent or dissociable binding.
A
Albumin
23
Q
Albumin: consists of 585 AAs arranged in _________ held together by __________ between cysteine residues.
A
Nine loops. Disulfide bonds.
24
Albumin: primary sequence of albumin contains three major regions with ______________ each, suggesting that it arose from gene duplication of some ancestral gene in a tandem rearrangement process. It is also interesting to note that ________ has regions of homology with serum albumin, which may indicate a common ancestral gene origin for these two proteins.
Three peptide loops. a-fetoprotein.
25
Albumin: In addition to genetic abnormality of analbuminemia, many hereditary variants of albumin differ from the most common allotype, _______, by single amino acid substitution. These variants can be rapid or slow migrating compared with Alb A, leading to two distinct albumin peaks (_______) in the heterozygous state.
Albumin A. Bisalbuminemia.
26
Albumin: Up to ____ of albumin circulating in normal persons become glycosylated nonenzymatically, whereas up to _____ becomes glycosylated during hyperglycemia in analogy with glycosylated hgb.
8%. 25%.
27
Albumin: halflife of circulating albumin is about _________, so that measurements of the glycosylated form may be useful in monitoring diabetic control during an interval of few weeks.
17 days
28
Albumin: can be very useful for assessing diabetic control in patients with hemolytic anemias whose red cell survival is greatly shortened and in whom measurement of glycosylated hgb is unreliable.
Fructosamine
29
Albumin: Glycosylated albumin requirements may not be reliable for assessing diabetic control in patients with ____________, in which albumin clearance is accelerated. Unlike patients under hemodialysis.
Protein losing neuropathy
30
Albumin: has an additional hexapeptide at its amino-terminal end.
Proalbumin
31
Albumin: On storage for many days, albumin forms covalently linked dimers through __________, resulting occasionally in an extra band of albumin on electrophoresis.
Free cysteines
32
Albumin: Elevations of serum albumin are infrequent, although they do occur in ________ as the plasma water phase shrinks. It should increase upon fluid therapy.
Dehydration
33
Albumin: Elevation of serum albumin may also occur artifactually as the result of prolonged application of ________ for venipuncture. Increase hemodynamic pressure from venous backup forces water and small solutes out of the intravascular space, thereby concentrating cellular elements, micellar forms of lipoproteins, and proteins such as albumin.
Torniquet
34
Albumin: sensitive but nonspecific reduction of albumin in so many different condition has led to its being termed a
Negative acute phase reactants
35
Albumin: Measurements of albumin concentrations are vital to the understanding and interpretation of _______ & _______ levels because these ions are bound to albumin.
Calcium & Magnesium
36
Albumin: shows a major polyclonal increase of immunoglobulins if the y fraction and nephrotic syndrome shows high levels of ________.
Cirrhosis. A2 macroglobulin.
37
Albumin: The presence of albumin in the urine is generally considered abnormal even in trace amounts, although some healthy individual exhibit _________ following intense exercise.
Albuminuria
38
Albumin: can be assessed by the quantitative measurement of albuminuria, as it tend to appear ahead of other serum proteins in urine during the course of renal glomerular damage.
Diabetic neuropathy
39
Albumin: is now considered a standard of care for management of DM and the early detection of diabetic complication.
Immunologic measurement of microalbumin
40
Albumin: the nephrotic syndrome which is marked by extensive _________, is often due to diabetic neuropathy or one of several other primary glomerular diseases.
Hypoalbuminemia
41
Most abundant a-1-globulin, is the most important protease inhibitor in plasma. Increased in neonatal hepatitis. One of the serum glycoproteins that rise in response to acute inflammation.
A-1-Antitrypsin
42
A-1-Antitrypsin coded by _______ on the chromosome ___.
SERPINA1. 14.
43
A-1-Antitrypsin: majority are __ alele or phenotype ___.
M. MM.
44
A-1-Antitrypsin: while some are heterozygous with M & Pi of other _____________ system.
Protease inhibitor
45
A-1-Antitrypsin: 2% carry Piz alele, with phenotype MZ with reduced ___.
AAT
46
A-1-Antitrypsin: are susceptible for pulmonary or hepatic disease
ZZ homozygous
47
A-1-Antitrypsin: _____ variant of allele are moderately reduced AAT expression but without any disease associated
Pis
48
A-1-Antitrypsin: suspected of increased lung and hepatic diseases.
SS & SZ phenotype
49
A-1-Antitrypsin: can be recognized by being phenotyped by _____________ and genotype with molecular assay.
Isoelectric electrophoresis
50
A-1-Antitrypsin: is used for screening of targeted population for early recognition of AAT deficiency
Genetic testing
51
Largest major macroglobulin protein in plasma. MW 725 000 Da. Women have higher levels than men in response to _______. Rises 10 fold or more in the __________ when the other lower molecular weight proteins are lost. The loss of ____ into urine is prevented by its large size.
A2 Macroglobulin. Estrogen. Nephrotic syndrome. AMG.
52
The net result is that AMG reaches serum levels equal to a greater than those of albumin ( _____g/dL) in the _______, which has the effects if maintaining oncotic pressure. There is also enhanced _____ synthesis.
2-3. Nephrotic syndrome. AMG.
53
A-1-Antitrypsin: AMG inactivates _______ by complexing with them and forming covalent bonds to them. Its own conformation is thereby altered which enhances clearance by the __________ system.
Proteases. Reticuloendothelial system.
54
A-1-Antitrypsin: Molecular forms of AMG
Sialic acid, Mannose & Galactose
55
A-1-Antitrypsin: Molecular forms of AMG can be separated by
Isoelectric focusing
56
A-1-Antitrypsin: The spectrum of inhibition by AMG is very wide, including virtually all types of
Serine, carboxyl, thiol & metal proteases
57
Migrating the a2 region. Combines with Hgb released by lysis of red cells in order to preserve body iron and protein stores. Circulating half life free of haemoglobin is roughly _______.
Haptoglobin. 4days.
58
Haptoglobin: hgb-haptoglobin complexes are removed from the circulation within minutes by the ___________, where the hgb is broken down into heme & globin which further degrades to ______ & ______.
Reticuloendothelial system. Iron & Bilirubin.
59
Haptoglobin: When the hgb binding capacity of the haptoglobin is exceeded, the free hgb enters the glomerular filtrate as ______________ that are subsequently reabsorbed in the proximal renal tubules and converted to ________.
A-chain-B-chain dimers. Hemosiderin.
60
Haptoglobin: rises in response to stress, infection, acute inflammation, or tissue necrosis probably by stimulation of synthesis.
Serum haptoglobin
61
Haptoglobin: Low haptoglobin concentrations may accompany ________ when hepatic systemic capacity is impaired. Concentration falls after __________, massive hemolysis in situations of hemolytic transfusion reaction, thermal burns, or autoimmune hemolytic anemia.
Liver disease. Hemolytic episode.
62
Haptoglobin: Low serum haptoglobin suggests
Hemoglobinuria (hemolysis)
63
Haptoglobin: High serum haptoglobin suggests
Myoglobinuria
64
A separate fraction of B-globulin consists of ___ component of complement.
C3
65
Complement: this protein can be resolved easily with fresh serum sample, in stored specimens and commercial control serum that has been _________, C3 is cleaved from ______, which migrates anodally to native C3 as a band nondistinct from other ________.
Lyophilized. C3c. B globulins.
66
Complement: Depression of C3 occurs in __________ when the complement system is activated and C3 becomes bound to i,mune complexes deposited in tissues, thereby removing them from plasma.
Autoimmune disorder
67
Complement: is a convenient marker for assessing disease activity in rheumatic disorders such as SLE & RA.
C3 (and also C4)
68
Complement: ____ is not appreciated on serum protein electrophoresis because its concentration is normally only about 1/5 that of ___.
C4. C3.
69
Complement: Both C3 & C4 are now easily quantitated by ________ for monitoring rheumatic disease activity.
Nephelometry
70
Plasma contains 100-400mg/dL of this, most abundant of the coagulation factors and which forms the fibrin clot. With an overall MW of 340,000 Da. It is a dimer consisting of three pairs of peptide chains(A-a, B-b & Y) linked with multiple disulfide bonds near the amino terminal ends.
Fibrinogen
71
Fibrinogen: cleaves fibrinopeptides A & B from the amino ends of the A-a & B-b chains, thereby resulting in a fibrin monomer that polymerizes into fibrils that macroscopically form a fibrin clot.
Fibrinogen
72
Fibrinogen: produces covalent bonds between lysine & glutamine residues of adjacent y-chains of diff fibrin molecules
Factor XIII
73
Fibrinogen: exhibit impairment of clotting and a hemorrhagic diathesis, whereas others show increased tendency to ________.
Dysfibrinogenemias. Thrombosis.
74
Fibrinogen: which essentially no fibrinogen is synthesized, results in hemorrhagic disorder that paradoxically is not as severe as the hemophilias in terms of joint abnormalities secondary to hemorrhage.
Congenital Afibrinogenemia
75
Levels may become elevated with the other _________to over 1.0mg/L. The ______ is also markedly elevated owing to fibrinogen content directly.
Fibrinogen. Acute phase reactants. ESR.
76
Fibrinogen: Finriinogen levels also rise with _______ & use of ________.
Pregnancy. Contraceptive medications.
77
Fibrinogen: Fibrinogen is absent for normal serum but should appear in plasma electrophoresis as a distinct band between the _____ & _____.
B & Y globulins
78
Migrating with a2 globulins is a copper binding protein which contains most of the copper in the plasma and exhibits ferroxidase activity that is important in iron metabolism.
Ceruloplasmin
79
Ceruloplasmin: it is synthesized in the _______, it has a mw of 132,000 Da and consists of a single polypeptide chain. Although lower at birth, serum levels are ______mg/dL in normal adults with 2 fold elevations found in oral contraceptive therapy and pregnancy or as an acute phase reactant.
Liver. 20-40.
80
Ceruloplasmin: Each molecule of ceruloplasmin can bind ________ of copper, which imparts a blue color of the protein. the combination of this blue with the yellow from the other chomogens of plasma imparts a _______ color to plasma with elevated ceruloplasmin concentrations, this is noted in bags for BT.
6 atoms. Greenish.
81
Ceruloplasmin: Iron is oxidized from ferrous to _______ ions by ceruloplasmim, which may be means of releasing iron from ferritin for binding to _________.
Ferric. Transferrin.
82
Ceruloplasmin: results from disordered copper metabolism in which hepatic excretion of copper into the bile is impaired leading to toxic deposition of copper into tissues.
Wilson's disease(hepatolenticular degeneration)
83
Ceruloplasmin: treatment for wilson's disease
Long term chelation w/ penicillamine
84
Ceruloplasmin: management for severe wilson's disease
Liver transplantation
85
Ceruloplasmin: Diagnosis of Wilson's disease is based on _________, measurement of low serum ________ levels and increased ________ concentrations in urine and on liver biopsy.
PD. Ceruloplasmin. Copper.
86
Ceruloplasmin: Physical findings in Wilson's disease
Liver dse, neurological signs & kayser-fleischer ring in the cornea
87
Ceruloplasmin: mutations in ceruloplasmin gene leading to __________ result in iron overload affecting pancreas, liver and brain with a spectrum of neurologic disease.
Aceruloplasminemia
88
Vitamin D binds to the group specific component which migrates as an a1-globulin. Mw is 51,000 Da. Decrease in liver disease. Normal serum concentration is ________. Binds Vitamin D and its metabolites on a mole-per-mole basis, but in plasma, it probably is not fully saturated.
Gc-Globulin. 20-55mg/dL
89
Gc-Globulin: has two _________ codominant alleles expressed as three phenotypes 1-1, 2-2 & 1-2. Congenital absence of this protein may be a lethal mutation,owing to impairment of ________ transport because it has low solubility in aqueous media.
Alleles. Vit.D
90
Gc-Globulin: results in urinary loss of DBP, some of which is complexed with Vit.D may contribute subsequent problems of calcium metabolism encountered.
Nephrotic syndrome
91
Gc-Globulin: it can be quantitated by
Radioimmunoassay, Radioimmunodiffusion & Rocket immunoelectrophoresis.
92
Gc-Globulin: have shown lower levels of Gc-Globulin in trauma patients who develop organ dysfunction and sepsis.
Immunonephelometry
93
Has a very high carbohydrate content which minimizes its visualizations by standard protein strains. Mw of 44,000 Da. Passes into glomerular filtrate to a large extent. ______ half life in the circulation. An acute phase reactant.
a1 Acid Glycoprotein
94
a1 Acid Glycoprotein: serum levels are normally ______mg/dL with elevations during pregnancy. May be important in the transport and metabolism of _________. Also binds some drugs and keep them in an inactive circulating pool.
40-105mg/dL. Progesterone.
95
a1 Acid Glycoprotein: Used in interpreting level of drugs such as _______ that may achieve high serum concentrations without expected therapeutic effect owing to being complexed in inactive form to higher than normal amount of a1 acid glycoprotein.
Lidocaine
96
a1 Acid Glycoprotein: Not widely used but it is recognized with its ability to bind various drugs such as ____________ inhibitor ST1571 and drug inactivation.
Tyrosine Kinase
97
Serve as a general scavenger molecule. Mw is 118,000-144,000 Da with substantial carbohydrate content. Normal serum concentrations are 100 ng/mL @ birth, 170 ng/mL in children and _________ng/mL in adults. Highly sensitive acute phase reactant. Used as a rapid test for presumptive diagnosis of bacterial infection & to monitor autoimmune disease.
C-Reactive Proteins. 470-1340 ng/mL.
98
C-Reactive Proteins: by electrophoresis, CRP is a _________ that may form a minor but distinct monoclonal appearing band in patients having severe inflammatory response.
Y-migrating protein
99
Highly specific for neutralizing chymotrypsin which cleaves peptide bonds at the carboxyl side of tyrosine & phenylalanine residues. MW 68,000 (25% CHO content) NV is ______mg/dL. Can rise rapidly five times normal as an acute phase reactant that remains elevated throughout a period of inflammation. Complexes with __________ measured as the bound form of PSA by immunoassay. It can be lost along with other low molecular weight serum proteins in the proteinuria of nephrotic syndrome.
a1 Antichymotrypsin(AAC). 40-60. Prostate-Specific Antigen.
100
A glycoprotein. Mw is 160,000 Da. NV is ______. Does not rise appreciably as an acute phase reactant. Role in disease states is preventing autodigestion of tissues by endogenous cellular enzymes.
Inter-a-trypsin inhibitor (IATI)
101
Role in neutralizing thrombin which normally becomes activated intravascularly from prothrombin during clot formation. 62,000 Da protein. Forms a covalently bonded complex with thrombin over a period of several minutes when mixed in solution. Essential for successful therapeutic administration of heparin, it instantaneously forms a complex with thrombin after the addition of heparin. Levels maybe depressed in severe liver disease or in protein losing disorder and in DIC.
Antithrombin III (ATT)
102
Response to stressful or inflammatory states like infection, injury, surgery, trauma or other tissue necrosis.
Acute Phase Reactants
103
Leukocytes releases proteolytic enzymes in tissue that must be neutralized by enzyme inhibitors to limit their extent of destruction.
Inflammation
104
Scavenger proteins which help collect and transport cellular debris and breakdown products to phagocytic cells (reticuloendothelial system) to process them and conserve vital substances. Healing of wounds requires a large amount of fibrin which arrives via the circulation as ________.
Haptoglobin & CRP. Fibrinogen.
105
Total Physiologic response in APR: induction of
Feve
106
Total Physiologic response in APR: recruitement of
Leukocytes
107
Total Physiologic response in APR: catabolism of
Muscle
108
Total Physiologic response in APR: shift in _______ synthesis
Protein
109
Total Physiologic response in APR: reduction in _______ production
Albumin
110
Protein abnormalities: patterns of __________ d/t malnutrition or gross loss of protein show decreases in all fractions, but the most dramatic reduction is often seen in albumin compared with its normally high value as the most abundant serum protein.
Hypoproteinemia
111
Protein abnormalities: Severe starvation, malabsorption or inanition associated with chronic disease will show marked reduction in albumin levels below ______. The other serum proteins including AAT, AMG, C3, Haptoglobin & Transferrin appear even fainter on electrophoresis.
20g/L
112
Protein abnormalities: Reduction in staining intensity for the _______ parallels a marked decrease in serum cholesterol concentration. The immune system is strongly affected by severe starvation with decreased synthesis of immunoglobulins resulting in ___________ and impaired resistance to bacterial and other infections.
B-Lipoprotein. Hypogammaglobulinemia.
113
Protein abnormalities: shows a variation in the hypoproteinemia pattern, in which most fractions are diminished owing to the combination of decreased synthesis and increased loss, although a2 may be relatively higher owing to a coexisting APR (_________) or to preferential retention of larger molecules (________).
Protein-losing Enteropathy. Haptoglobin. a2 macroglobulin.
114
Protein abnormalities: Specific loss of proteins into the urine as in nephrotic syndrome occurs on a
Molecular weight basis
115
Protein abnormalities: due to impaired renal tubular reabsorption of small proteins shows a pattern of a,B & y in the urine with only minimal albumin loss into the urine.
Tubular proteinuria
116
Protein abnormalities: Acute phase or immediate response patterns have greatest effect on serum protein electrophoresis by increasing the amount of ________ while slightly decreasing the concentration of albumin.
Haptoglobin
117
Protein abnormalities: it can contribute to chronic, acute or stressful stimuli response
AAT
118
Protein abnormalities: If the haptoglobin has been depleted in a patient as a result of active hemolysis, an independent band of hemoglobin may be migrating in the ________ region.
B or a2
119
Protein abnormalities: Pattern of _____________ is an extension of the acute phase response(high haptoglobin, slight reduction in albumin) with greater decrease in albumin and polyclonal increase in immunoglobulins broadening the ________.
Delayed response/Chronic pattern. Y region.
120
Protein abnormalities: A striking elevation of transferrin in the B-region sometimes occurs in patients suffering from _________. The increase in _______ corresponds to increased IBC, and the percent saturation is low. This variation may be confused with a _______ protein because the transferrin band forms a narrow, clonal-appearing band.
Iron deficiency anemia. Transferrin. Myeloma.
121
Protein abnormalities: ______ of the liver creates a protein pattern that is recognizable. Hepatocellular damage from cirrhosis results in diminished capacity to synthesize _______.
Cirrhosis. Albumin.
122
Protein abnormalities: Portal hpn secondary to cirrhosis leads to the formation of __________, which contains almost exclusively albumin.
Ascitic fluid
123
Protein abnormalities: _________ in the CSF are used to indicate immunologic activity in the CNS and occur in infectious diseases or autoimmune or demyelinating diseases.
Oligoclonal bands
124
Protein abnormalities: is manifested as a completely absent y fraction, it occurs normally in neonates before maturation of the immune system. It also occurs in some congenital immunodeficiency states such as ___________.
Hypogammaglobulinemia. Bruton's Agammaglobulinemia.
