PLASMA PROTEINS

1. Simple Proteins

2. Conjugated Proteins

• two classificiation of proteins

Simple Proteins

• they contain peptide chains which on hydrolysis yield only on amino acids

Simple Proteins

• they may be fibrous or globular in shape

1. Fibrinogen

2. Troponins

3. Collagen

• simple proteins that are fibrous in shape

1. Hemoglobin

2. Plasma Proteins

3. Enzymes

4. Peptide Hormones

• simple proteins with globular shape

Globular Proteins

• type of simple protein that are usually compact and have little or no space for water in the interior of the molecule

Conjugated Proteins

• a classification of proteins that are composed of a protein and a nonprotein moiety

Nitrogen Balance

• balance between anabolism and catabolism

Prealbumin (Transthyretin)

• migrates ahead of albumin

• half life: 2 days

Prealbumin

• rich in tryptophan and contains 0.5% carbohydrate`

Prealbumin

• has significant beta-pleated sheet conformation

• serves as transport protein for thyroxine

Prealbumin

• tranpsorts retinol or vitamin A by complexing with retinol-binding protein

Prealbumin

• used to detect malnutrition and the individual’s response to dietary supplementation

Prealbumin

• used as a landmark to confirm that the specimen is really CSF

• crosses more easily into the CSF than other proteins

1. Alcoholism

2. Chronic Renal Failure

3. Steroids

1. Poor Nutrition

• causes increased prealbumin

• causes decreased prealbumin

Nephelometry

18-45 mg/dL

10-mg/L

• method for prealbumin

• ref range for prealbumin

• conversion factor for prealbumin

Albumin

• most abundant protein in plasma

• general transport protein

• maintains osmotic pressure

Albumin

• indicator of nutritional status

• serves as circulating reservoir of amino acids

• sensitive and a marker of cystic fibrosis

Albumin

• negative acute phase reactant exhibiting decreased level in acute inflammatory processes

Nephrotic Syndrome

• clinical significance of albumin with lowest level in this condition

Dye Methods (Bromcresol Green and Purple)

3.5-.5.0 mg/dL

10-g/L

• method for albumin

• ref range for albumin

• conv factor for albumin

Globulin

• group of proteins consisting of alpha 1, alpha 2, and gamma fractions

Globulin

• measured by substracting the value of serum albumin from the total protein concentration

Early Cirrhosis

• Clinical significance of globulin with increased concentration

• causes a balance loss of albumin and normal levels of total protein

Indirect Method (Globulin = Total Protein - Albumin)

2.3-3.5 g/dL

10-g/L

• method for globulin

• ref range for globulin

• conv factor for globulin

Alpha-1-Antitrypsin (AAT)

• an acute phase reactant

• glycoprotein

• coded for by the SERPINA1 (Pi) gene on Ch14

SERPINA1 on Ch14

• codes for alpha-1-antitrypsin

alpha-1-antitrypsin

• major inhibitor of protease activity in plasma, preventing self-destruction of tissues

Alpha-1-antitrypsinn

• candidate for treatment of COVID-19 due to its antiviral and anti-inflammatory effects through inhalation and parenteral

alpha-1-antitrypsin

• neutralizes trypsoin-like enzymes such as eutrophil elastase

Neutrophil Elastase

• enzyme that is released from WBC to combat infection

PIZZ, PISS, PISZ, PIMZ

• genotypes of alpha-1-antitrypsin (pathogenic alleles)

PIZZ

• presence of this genotype is related to AAT deficiency and a risk factor for emphysema

Severe AAT Deficiency

• a rare autosomal codominant genetic condition caused by mutations of the SERPINA1 gene

  • Caucasian

1. Inflammation

2. Pregnancy

3. Contraceptives

1. Emphysematous Pulmonary Diseases

2. Juvenile Hepatic Cirrhosis

• causes increased AAT

• causes decreased AAT

1. Nephelometry

   Turbidimetry

   EIA

   RIA

2. 145-270 mg/dL

3. 0.01-g/L

• methods for AAT

• ref range for AAT

• conv factor for AAT

Alpha-1-Fetoprotein (AFP)

• glycoprotein that migrates between albumin and alpha-1 globulin band

AFP

• synthesized initially by the fetal yolk sac and then by fetal parenchymal cells of the liver

• most abundant protein in fetal serum

AFP

• peaks in fetus at 13 weeks of gestation

• detectable in maternal blood

Maternal Serum AFP

• physiologically increased in the presence of twins (transmitted across the placenta)

AFP

• no known function for adults

Maternal Serum

Amniotic Fluid

• samples for gestational disorder test for AFP

Immunochemical Test, RIA, EIA

5ng/mL

• method for AFP

• ref range for AFP

1. Neural Tube Defects

2. Down Syndrome

3. Ataxia Telangectasia

• fetal abnormal conditions that is screened using the maternal serum AFP

AFP

• tumor marker for hepatic and gonodal cancer

1. Hepatoma

2. Gonodal Cancer

3. Tyrosinosis

4. Cirrhosis

5. Hepatitis

6. Malignancy

• causes increased AFP in non-pregnant/post-natal

1. Neural Tube Defects

2. Anencephaly

3. Spina Bifida

4. Atresia of GIT

5. Fetal Distress

6. Ataxia Telangectasia

• causes of increased maternal serum for AFP

Down Syndrome

Edward Syndrome

• causes of decreased maternal serum for AFP

Alpha-1-Acid Glycoprotein (Orosomucoid)

• synthesized in the liver

• contains high percentage of carbohydrate and sialic acid

AAG

• greatest affinity for progesterone and binds drugs

AAG

• useful for diagnosing bacterial infections in neonates

True

T or F

AAG has similar AA sequence with Igs

1. Pregnancy

2. Cancer

3. Pneumonia

4. RA

5. Cell Proliferation

• causes increased AAG

Nepholmetry, Immunoassay

55-140 mg/dL

0.01-g/L

• method for AAG

• ref range for AAG

• conv factor for AAG

Alpha-1-Antichymotrypsin

• synthesized in the liver and partly by pancreas

Alpha-1-Antichymotrypsin

• coded by SERPINA3 gene in Ch14

Alpha-1-Antichymotrypsin

• acute phase reactant that is a serine protease against neutrophil cathepsin G

Alpha-1-Antichymotrypsin

• binds and inactivates PSA

1. Alzheimer’s

2. Malignancy

3. Infection

4. Burns

5. AMI

1. Liver Dx

• causes increased Alpha-1-Antichymotrypsin

• causes of decreased Alpha-1-Antichymotrypsin

RIA

30-60 mg/dL

• method for Alpha-1-Antichymotrypsin

• ref range for Alpha-1-Antichymotrypsin

Hemopexin

• binds heme released by degradation of hemoglobin

• strongest affinity for heme

nephelometry

50-115 mg/dL

• method for hemopexin

• ref range for hemopexin

Group-Specific Component Globulin

• exhibits affinity with vitamin D and actin

Gc-Globulin

• migrates in the alpha-q and the alpha-2 interzone during electrophoresis

RIA

20-55 mg/dL

• method for Gc-Globulin

• reference range for Gc-Globulin

Haptoglobin

• an alpha 2 glycoprotein and an acute phase reactant

Haptoglobin

• has two heavy chains and two light chains linked by disulfide bonds in analogy to the basic structure of immunoglobulins

Haptoglobin

• binds free hemoglobin by its alpha chain

Haptoglobin

• prevents the loss of hemoglobin and its constituent iron into the urine

Haptoglobin

• evaluates degree of intravascular hemolysis (HTR and HDN)

Haptoglobin

• for monitoring patients who have slow but steady rate of red cell destruction, such as by mechanical heart valves, hemoglobinopathies, or exercise-associated trauma

haptoglobin

• its reduction is a reliable marker for the rapid identification of accelerated in vivo RBC damage irrespective of the site of hemolysis

True

T or F

Haptoglobin is slightly decreased after blood transfusion

CD163

• receptors that allow monocytes and tissue macrophages to uptake haptoglobin-hemoglobin complexes formed during red cell breakdown

True

T or F

Haptoglobin can be used to evaluate rheumatic diseases

False (decreased)

T or F

Haptoglobin is increased in intravascular hemolysis and hemoglobinuria.

1. RIA

   Immunonephelometry

2. 26-185 mg/dL

• methods for haptoglobin

• ref range for haptoglobin

Ceruloplasmin

• copper-binding alpha2 glycoprotein that has enzymatic activity

Blue

• color imparted by the ceruloplasmin

Wilson’s Disease

• clinical significance of ceruloplasmin

• marker for this

Wilson’s Disease

• disorder caused by mutations in the ATP7B gene on ch13

ATP7B on Ch13

• mutation in Wilson’s Disease

Deposition of copper in skin, liver, brain cornea (Kyser-Fleisher Rings)

• clinical features of Wilson’s Disease

0.1 g/L (decreased)

• amount of ceruloplasmin that indicates Wilson’s Disease

1. Immunoassay

   Copper Oxidase Activity

2. 18-45 mg/dL

• methods for ceruloplasmin

• ref range for ceruloplasmin

alpha-2 Macroglobulin (AMG)

• largest major non-immunoglobulin protein in plasma

AMG

• does not diffuse from the plasma space

• inhibits trypsin, pepsin, and plasmin

AMG

• forms a complex with PSA

False (large size, cannot)

T or F

AMG is normally present in urine due to its small size.

1. Nephrotic Syndrome

2. DM

3. Liver Disease

• increased AMG

1. RIA

   EIA

   Immunonephelometry

   Latex Agglutination

2. 150-420 mg/dL

• methods for AMG

• ref range for AMG

Beta-2 Microglobulin (B2M)

• light chian component of the major HLA, encoded by the B2M gene

B2M

• found on the surface of most nucleated cells

• present in high concentration on lymphocytes

B2M

• for synthesis of CD8 cells

B2M

• freely filtered at the glomerulus and then reabsorbed and completely metabolized by the proximal tubule

B2M

• has a tendency to fold into a beta sheet configuration, resulting in amyloid formation

Silk Road Disease (Neuro-Behcet Syndrome)

• clinical significance for B2M

• inflammation of the BV, affecting white matter portion of the brain, eyes, GIT, skin, and genitals with stiff neck, personality disorder, poor eye vision, sores or ulcerations, bloody stool, and joint pain

1. Renal Failure

2. Multiple Myeloma

3. RA

4. SLE

5. HIV

• increased B2M

Immunoassay

0.2-2.8 ug/dL

• method for B2M

• ref range for B2M