Test 2: Proteins Flashcards
What are two transport proteins that act as buffers?
albumin and hemoglobin
Transferrin can carry ____ iron and is usually only _____ saturated.
2, 1/3
Most proteins are ________ amino acids and synthesized in the liver.
200-300
What is the functional unit of the liver?
lobule
Immunoglobulins come from _______ cells.
Hb comes from __________.
plasma
bone marrow
There are ____ pyrrolines is heme with alternating double bonds.
4
What can be broken down to make immunoglobulins. Acts like storage
albumin
Where does AA absorption take place?
Ileum & Jejunum
Excess AA get degraded in the liver and is stored as…
“fat”
What partialy digests proteins?
stomach (HCL and pepsin)
[aa] blood: ______ mg/dl
35-65
Protein turnover rate is ______ g/day
125-220
Kidney Filters & reabsorption:
_________ g/dl of protein gets exreated in urine.
~7g/dl (150-300mg/24h)
1/3 of normally excreted protein is “ ___________ Protein”
Tamms Horsfall AKA Uromodulin (thick ascending loop of Henle)
What are the two protein catabolism pathways?
-Lysosomal pathway: Intra & extracellular proteins
-Cytosolic pathway: Intracellular proteins
Central catabolic reaction where amino can become keto and keto can become amino through pyridoxal phosphate.
Transamination/“Transaminase”
What are the exception of transamination?
Lysine, threonine, proline, hydroxyproline
Total protein = ________ + ________
Albumin, Globulin
When total protein goes down it is due to decreased ________.
albumin
-sign of hepatic damage (not in early stage)
When total protein goes up is it due to increased ___________.
Globulin.
-caused by inflammation
What is the A/G ratio used for?
to understand hepatic conditions more and with cirrhosis
Normal A/G ratio?
*** 1:1 - 1.5:1
1.5:1 - 2.5:1
Total protein is approx…
6.5-8.3 g/dl
Total albumin is approx…
3.5-5.5 g/dl
Hemoconcentration & Hemodilution are __________ protein concentration changes in the blood.
relative
Hemoconcentration & Hemodilution there is no change in A/G ratio. The change is mainly due to what change?
plasma volume change
Low body H20 —–>
“Hemoconcentration”
Excess body H20 —>
“Hemodilution
What conditions effect water balance?
-Cushings
-Adison’s disease
-
-
Is Hypoproteinemia or Hyperproteinemia more common?
Hypoproteinemia
What can cause hyperproteinemia?
-Dehydration (most common)
-Increased γ-globulin
-myeloma
-Waldenstrom’s macroglobulinemia
-chronic infection
How does myeloma cause hyperproteinemia?
effects the kidneys (clogs glomerulus)
makes lots of immunoglobulins (but of bad quality)
known as non-hodkins lymphoma or lymphoplasmacytic (plasma cells)
Waldenstrom’s macroglobulinemia
What two renal conditions cause hypoproteinemia?
✴Nephrotic syndrome or Nephrosis
What conditions can cause hypoproteinemia?
1.Excretion in urine in renal disease
2.Leakage into the GI tract (“spruce”, malabsorption)
3.Loss of blood
4.Decreased Intake
5.Decreased synthesis
6.Increased protein catabolism
✴Burn, Trauma, increased energy demand
[pregnancy]
What are two Negative Acute Phase Reactants?
albumin and transferrin***
protein that decreases in acute phase
negative phase reactant
protein that increases in the acute phase.
-acute phase reactant
-acute phase protein
Acute phase reaction (or protein) is the response to…
the acute inflammation!
Acute phase reactants involves what functions?
defense or protective function
Why is C reactive protein (CRP) useful?
baseline levels are low, can dramatically increase
What are the immune acute phase reactants?
-Αmyloid P component (Serum)
-Mannose binding lectin (MBL)
-Complements
What are the coagulation acute phase reactants?
-Fibrinogen
-Prothrombin
-Factor VIII von willebrand factor
-Plasminogen activator inhibitor (PAI-1)
The only protein that increases increases in blood samples of nephrotic syndrome (cannot go through glomerulus)
α2 macroglobulin
What acute phase reactant down regulates inflammation?
α1-antitrypsin***
What are all the acute phase reactants?***
-CRP
-Αmyloid P component (Serum)
-Mannose binding lectin (MBL)
-Complements
-Fibrinogen
-Prothrombin
-Factor VIII von willebrand factor
-Plasminogen activator inhibitor (PAI-1)
-α2 macroglobulin
-Ferritin
-Ceruloplasmin
-Haptoglobin
-α1-antitrypsin
-α1-antichymotrypsin
What are the negative phase reactants?***
-Albumin
-Transferrin
-Transthyretin
-Retinol binding protein
-Antithrombin
-Transcortin (also called corticosteroid binding globulin, or serpin 6)
thyroid hormone carrier, prealbumin
Transthyretin
retinol (Vit A) carrier protein
Retinol binding protein
Transcortin is also called?
corticosteroid binding globulin, or serpin 6
it is a cholesterol carrier
What negative phase reactant is associated with protein and nutrition status?
pre albumin
What are the fat soluble vitamins?
Vitamins A, D, E, and K
What is the normal BUN/creatinine ratio?
10:1 - 20:1
If both BUN and creatinine is elevated, ratio will still appear normal…. What could this indicate?
renal disease
Pre-renal acute failure is usually due to altered ___________ function.
Cardiovascular
Serum BUN creatinine ratio grater than 20:1 is observed in patients with…
-pre-renal azotemia*** (accumulation of nitrogenous products in blood)
-gastrointestinal bleeding
-excessive protein intake
-post-renal azotemia
What is the difference between positive acute phase reactants and negative acute phase reactants?
*Negative acute phase reactants are downregulated, and their concentrations decrease during inflammation
(shunted to other protein needs, required in the current inflammatory process)
Positive acute phase reactants are upregulated, and their concentrations increase during inflammation.
When using an alkaline buffer with serum protein electrophoresis, where is the sample loaded?
the middel!
What is the order on serum protein electrophoresis (+ to -)
-pre-albumin
-albumin
-a1-anti trypsin, a1-acid glycoprotein
-a2-macroglobulin, haptoglobin
-hemopexin, transferrin, beta-lipoprotein, C3
-immunoglobulins
Biologically active form of thyroid hormone =
Inactive form =
T3 (3 iodine)
T4 (4 iodine)
[transthyretin (TTR) / thyroxine-binding prealbumin (TBPA)]
Prealbumin???
Serves as a transport protein for a small fraction of thyroid hormones,
esp. thyroxine
Prealbumin
Prealbumin also binds with ____________ protein to transport retinol (Vitamin A)
retinol-binding
True or false:
Pre-albumin is typically seen on SPE
False
What is a VERY sensitive marker of poor protein nutritional status?***
Prealbumin
Decreased in hepatic damage (can be produced here), acute phase inflammatory response,
& tissue necrosis***
Prealbumin
Prealbumin is increased in what patients?***
patients receiving steroids, & chronic renal failure (because it can go through the glomerulus)
What is the half-life for albumin and prealbumin?
albumin - 20 days
prealbumin - 2 days (because it can go through the glomerulus)
Normal range for albumin?
3.5-5.5 g/dl
MW: 66 kD (threshold of glomerulus)
Albumin makes up ______% of total protein.
50-60
What are the requirements for substance to be accurate for clearance testing.
-stable
-freely filtered
-no reabsorption
-no execration? (not an issue with inulin)
What charge is albumin>\?
extremely negatively charged
Albumin has a low pH of 4.0-5.8. In an alkaline buffer, moves rapidly towards the _______.
anode (+)
What are the main functions of albumin?
-maintenance of colloid osmotic pressure of intravascular fluid, binding subs. in the blood “negativity”
-oncotic pressure
-source of AA (neg. acute phase reactant
-buffering capacity
examples of substances in the blood that albumin binds to
Unconjugated bilirubin, salicylic acid, FA, Ca2+, Cortisol, & drugs
What are the two types of causes for hypoalbuminemia?
-Decreased production
-Increased loss/use after synthesis
What are the decreased production causes of hypoalbuminemia?
-Malnutrition (inadequate source of aa)
-Liver disease (not in early stage)
What are the loss/use after synthesis causes of hypoalbuminemia?
-GI tract loss via intestinal leakage
-Loss in renal disease (not reabsorbed)
-Burns (leakage)
-Ascites
-Inflammation/neoplasm
-Pregnancy (used by baby)
How is edema related to hypoalbuminemia?
decreased albumin causes the oncotic pressure to go down resulting in water leakage into tissues.
Causes of hyperalbuminemia?
-Relative increase
-Usually due to dehydration
-Rarely seen due to other reasons
-two peaks are seen for albumin
-Unusual molecular characteristics.
Does not appear to be harmful to
individual.
Bisalbuminemia (Genetic Origin)
Extremely low or absent albumin
Analbuminemia (genetic origin)
How is albumin measured?
-Chemical
-Electrophoresis
-Dye binding
~90% of α1 fraction
- APR
α1-antitrypsin
How is α1-antitrypsin measured?
Immunoassay**
Normal range for α1-antitrypsin?
0.2-0.4 g/dl
-neutralizes trypsin & trypsin-like enzymes
-protease inhibitor
α1-antitrypsin
“Neutrophil elastase” —> kills exogenous bacteria
What happens with α1-antitrypsin deficiency?
severe, degenerative, EMPHYSEMATOUS PULMONARY DISEASE (damage to the alveoli that can cause respiratory acidosis) and juvenile hepatic cirrhosis ***
How is α1-antitrypsin deficiency acquired?***
Chronic Liver Disease***
~ Severe protein deficiency
conditions
What can cause increased α1-antitrypsin?
Acute Phase Reaction, pregnancy, oral contraceptive use
Helps maintain the mucus layer in the first line of defense.
α1 ACID GLYCOPROTEIN (OROSOMUCOID) APR
low pI(2.7) even in the acidic solution, negative charged
α1acid glycoprotein (Orosomucoid)
maintaining mucus membrane integrity
cell membrane formation & fibers in association with collagen
α1acid glycoprotein (Orosomucoid)
What increases α1acid glycoprotein ?
Acute Phase Reaction, pregnancy, cancer, pneumonia, RA,
conditions related to the cell proliferation*
What causes decreased α1acid glycoprotein?
Inborn errors of metabolism
How is α1acid glycoprotein measured?
Immunonephelometry, Immunofixation, Immunoassay(s)
Why is α1acid glycoprotein not measured by SPE?
AAG: has high carb content, “NOT well stained in SPE”
What is detected in the fetus and cancer?***
α1-FETOPROTEIN (AFP)***
How is α1-FETOPROTEIN (AFP) measured?
**Immunoassay: RIA and EIA
When does α1-FETOPROTEIN (AFP) decrease?
8-12 months after birth
If α1-FETOPROTEIN (AFP) is detected in adults it means….
cancer (hepatic or gonad cancer)
-function not fully established in adult
α1-FETOPROTEIN (AFP) is detectable maternal blood during pregnancy up to _____ months
7-8
Used as screening test for several fetal conditions between 12 & 20 weeks
gestational age
α1-FETOPROTEIN (AFP)
What conditions are associated with elevated AFP?
Anencephaly, Spina bifida, neural tube defects, atresia, fetal distress, ataxia-telangiectasia (Louis-Barr Syndrome)
Also increased in Twins
What is associated with a low level of AFP?
3-4x increased risk for Down’s syndrome
What is used as a tumor marker in adults?***
α1-FETOPROTEIN (AFP)
80% is hepatocellular carcinoma
Any protein can be measured by ___________ if you have the antibody.
immunoassay
High Density Lipoprotein (HDL) is part of the _________ fraction.
α1-Globulin
Largest major nonimmunologic
circulating protein (mw 725 - 820 kD)
α2 MACROGLOBULIN
What are the functions of α2 MACROGLOBULIN?
✴ Neutralize enzymes, [thrombin, trypsin, pepsin, plasmin] (blocks substrate binding site)
✴ Carrier for zinc
✴ Role in the innate or nonspecific immune response
α2 MACROGLOBULIN is ___________ in nephrotic syndrome.
increased***
How is α2 MACROGLOBULIN measured?
✴ Nephelometry, Immunoassay
Coagulation factor II; converted to thrombin in process of coagulation; thrombin acts on fibrinogen to convert it to fibrin
PROTHROMBIN
PROTHROMBIN is decreased in…
liver disease, Vitamin
K deficiency
How is prothrombin measured?
prothrombin time
What factors are vitamin K dependent?
2,7,9,10
What is the function of thyroid binding globulin?
transport protein for T3 & T4
-major carrier
How is thyroid binding globulin measured?
*Immunoassay
-Indirect measurement is by T3 Uptake (currently decreasing in use), TBG binding capacity
What is the active form of iron?
ferric (Fe3+)
Fe3+ in food and gets converted to ferrous (Fe2+) to be absorbed and then to ferric (Fe3+) state to be used?
bind free Hb to prevent loss of Hb via urine, and to transport it to the liver
Haptoglobin (APR)
What can cause Haptoglobin to increase?
burns, nephrotic
syndrome, rheumatic disease, stress, infection, acute infection, tissue necrosis
What can cause Haptoglobin to decrease?
IV hemolysis
How is Haptoglobin measured? (must be free?)
✴ immunonephelometry,
✴ haptoglobin electrophoresis
✴ immunoassay
✴ Transport protein for copper
✴ Enzymatic activities:
✓ Cu oxidase, histaminase,
ferroxidase
Ceruloplasmin APR
What can cause Ceruloplasmin to increase?
inflammatory processes,
pregnancy, malignancies, oral estrogen therapy.
What can cause Ceruloplasmin to be decreased?
Wilson’s Disease (increased copper in tissues and urine but decreased in blood),
Menkes’ kinky-hair syndrome
How is Ceruloplasmin measured?
✴ Immunonephelometry
✴ immunoassay
enzyme that catalyzes the oxidization of iron II to iron III
Ferroxidase is present in ceruloplamin
Protein hormone produced in tubules of kidney (border of cortex and medulla)
✴ Stimulates erythropoiesis
-Acts on erythroid cell precursors in bone
marrow
Erythropoietin
An potent cytoprotective (anti-apoptotic)
hormone
Erythropoietin
■ Precursor to angiotensin I
■ After conversion to angiotensin II,
regulates, or increases blood
pressure via vasoconstriction
Angiotensinogen
VLDL: What is the major fat carried?
TG (endogenous)
Pre-beta?
α2 Lipoproteins (VLDL)?
What is part of the α2-Globulin Fraction?
-α2 MACROGLOBULIN
-PROTHROMBIN
-THYROID BINDING GLOBULIN
-Haptoglobin
-Ceruloplasmin
-Erythropoietin
-Angiotensinogen
What is part of the β-Globulin Fraction?
-β1 LIPOPROTEINS (LDL)
-FIBRINOGEN
-Plasminogen
-COMPLEMENT
-Transferrin (Dierophilin)
-C-1 ESTERASE INHIBITOR
-HEMOPEXIN
-β2 MICROGLOBULIN
-Coagulation Factor I
■ Converted to fibrin by thrombin
■ Acute phase reactant
FIBRINOGEN
What can cause increased fibrinogen?
inflammatory
conditions, pregnancy, oral
contraceptives
How is fibrinogen measured?
coagulation
Forms a distinct band between the β and γ areas when plasma is electrophoresed
Fibrinogen
-Fibrinolytic protein activated to enzymatic status (plasmin) in coagulation process
-Plasmin slowly lyses fibrin clots
Plasminogen
■ Fractions except C1 & C2
■ Enhances nonspecific cellular immune
response, such as phagocytosis,
anaphylaxis, lysis
COMPLEMENT
What can cause decreased compliment?
malnutrition, DIC, SLE, RA,
recurrent infection
How is compliment measured?
✴ immunonephelometry
✴ immunoassay
✴ CH50
✴ Total Hemolytic Complement
Inhibits C-1 esterase (activated C-1)
C-1 ESTERASE INHIBITOR
Deficiency in C-1 esterase inhibitor results in…
angioneurotic edema
-Function is to bind free heme (decreases oxidative damage)
-Increased in acute phase
reaction
Hemopexin
What decreases Hemopexin?
IV hemolysis &
hemolytic anemia
How is Hemopexin measured?
✴ Nephelometry
✴ Immunoassay
■ Light chain of HLA antigen
■ Found on surface of most nucleated cells, esp. high on lymphocytes
β2 MICROGLOBULIN
MW ~11 kD
■ Filtered by renal glomerulus, but 99% is
reabsorbed and catabolized in the proximal tubules
β2 MICROGLOBULIN
β2 MICROGLOBULIN is increased with
✴ tubular damage (poor clearance by kidney)
✴ Overproduction of certain cell types, such as occurs in certain inflammatory
diseases (RA, SLE)
-In HIV patients
a high β2 level in the
absence of renal failure indicates…
a large lymphocyte turnover, suggesting the viral
killing of lymphocytes as seen with HIV patients
How is β2 MICROGLOBULIN measured?
immunoassay
What is part of the γ-Globulin Fraction?
*C1 & C2
-immunoglobulins (igG, igM, IgA, IgD, and IgE)
■ Predominant immunoglobulin of the
secondary or anamnestic response
■ Crosses the placental barrier
■ Associated with long-term immunity
■ Highest concentration in blood of all immunoglobulins*
■ Usually reacts best at 37 degrees
IgG
■ First immunoglobulin to be produced in immune response
■ Dominant immunoglobulin in primary
immune response
■ Pentamer structure
■ Largest immunoglobulin
■ Isohemagglutinin (Blood group antibodies)
IgM
-Found both in blood and
on mucous membranes in
secretions
■ Exists as monomer and
dimer, possibly trimer
■ Associated with protection
of respiratory and
gastrointestinal disease
IgA
■ Function in serum unknown
■ Found on surface of mature
B lymphocytes as part of
antigen recognition system
of B-cells
■ Very low concentration in
serum
IgD
■ Associated with Type I
hypersentivities
■ Bound to mast cells in
tissues and basophils in
blood
■ Low concentration in serum
IgE
Highest concentration in blood of all immunoglobulins
IgG
