PLASMA PROTEINS

Plasma proteins

1. Total proteins :6 – 8gms%

2. Albumin : 3.5 – 5gms%
3. Globulin : 2.5 – 3.5 gms%
4. Fibrinogen : 200 – 400mg%
Includes conjugated proteins like
glycoprotein and lipoproteins
 synthesis
All plasma proteins except
immunoglobulin are synthesized
in liver
On membrane bound ribosome as
preproteins
rER sER Golgi apparatus

plasma secretory vesicle

 separation
Electrophoresis :
Movement of charged particles through an
electrolyte when subjected to an electric field
5 bands:
albumin (55-65%)
alpha 1 globulin(2-4%)
alpha 2 globulin(6-12%)
beta globulin(8-12%)
gamma globulin(12-22%)
 Albumin
• Normal level:3.5—5g/dl
• 60% of plasma protein
• Major part of plasma protein
• Molecular weight: 69000D
• 1 poly peptide chain with 585 amino
acids and 17 disulphide bonds
• Elliptical in shape
 Albumin
• 40% in plasma and 60% in extra cellular
space
• Synthesized by hepatocytes
• Albumin present in CSF and interstitial fluid
• Half life : 20 days
• Liver produces 12g albumin per day(25%)
 Albumin
Functions :
Colloid osmotic pressure
Transport functions
Buffering functions
Nutritional functions
 Colloid osmotic pressure

• Proteins cannot easily escape out of blood

vessels so provide Effective Osmotic
pressure (takes water into vascular
compartments)
• 80% by albumin; 20% globulins
• Albumin fluid out from vascular
compartment fluid collection in
interestial space OEDEMA
STARLINGS HYPOTHESIS
At the arterial end - BP 35mmHg & EOP 25mm Hg so water
moves out by a pressure of 10 mm Hg
At the venous end - BP 15mmHg & EOP 25mm Hg so water is
imbibed by a pressure of 10 mm Hg
So blood volume remains the same

BP –Blood pressure or hydrostatic pressure & EOP –Effective osmotic pressure

 Transport functions
Albumin transports the following

• Free Fatty acids , bilirubin,

• Drugs - Aspirin, Sulpha drugs,
Dicoumarol, Phenytoin
• Hormones - thyroxine, steroid
hormones
• Metals - calcium, copper
Buffering functions due to
• High concentration

• 16 histidine residues

Nutritional functions
Source of essential amino acids
 Albumin Clinical applications

1. Blood brain barrier

• Albumin –fatty acid complex cannot cross
blood brain barrier FA cannot be used by
brain
• Unconjugated bilirubin can cross the blood
Brain barrier in young children when replaced
by drugs on albumin deposited on brain
Kernicterus & mental retardation
2 Drug interaction
High albumin affinity drugs administered
together competition & displacement of
one drug ex phenytoin & dicoumarol
3. Protein bound calcium
Calcium is lowered by 0.8 mg /dl for a fall of
1g/dl of albumin(total Ca & ionised Ca
normal so no tetany)
4. Therapeutic use
Burns , hemorrhage & shock
 5 EDEMA – due to Hypoalbumenemia
(< 2 g / dl)
Causes :
• Cirrhosis of liver-synthesis is reduced
• Malnutrition-synthesis is reduced
due to decreased intake of food
• Nephrotic syndrome- Loss of albumin
through urine
• Protein losing enteropathy- decreased
absorption so loss through GIT
 Causes of Edema
1) Albumin is reduced(< 2 g / dl)
A) Malnutrition; generalised edema
B) Nephrotic syndrome; facial edema
C) Cirrhosis; Ascites
2) Congestive Cardiac Failure
pitting edema (feet)
Due to increased hydrostatic pressure in vein
 Analbuminemia
• Rare condition.
• Plasma of certain humans lack
albumin
• Defective mutation in the gene that
affect splicing is responsible for
absence
Albumin globulin ratio
• Normal ratio -1.2: 1 to 1.5:1
• In hypoalbuminemia there will
be a compensatory increase in
globulins which are synthesized
by reticuloendothelial cells
• A/G altered or reversal will lead
to edema
 Hyper gamma-
globulinemias
• Low albumin level in blood

• Chronic infections

• Multiple myeloma
 Transport protein
• Being a watery medium
• Lipids and lipid soluble
substances will not dissolve
• Such molecules are carried by
specific carrier molecule

Department of Biochemistry Govt Medical

College Kannur
 Albumin
Albumin transports the following

• Free Fatty acids , bilirubin,

• Drugs - Aspirin, Sulpha drugs,
Dicoumarol, Phenytoin
• Hormones - thyroxine, steroid
hormones
• Metals - calcium, copper
Department of Biochemistry
Govt Medical College Kannur
 PRE ALBUMIN(Transthyretin)

Named because of its faster mobility

Transthyretin or thyroid binding

Prealbumin carries thyroid hormones

Department of Biochemistry
Govt Medical College Kannur
 Retinol binding protein

Carries vitamin A
Lost in urine
Synthesized by liver
Level indicates vitamin A stores

Department of Biochemistry
Govt Medical College Kannur
 Thyroxin binding globulin

• Carrier molecule for thyroxin and

T3
• Increased in pregnancy and
decreased in nephrotic syndrome
• Synthesized in liver
• Used for studying TFT
Department of Biochemistry
Govt Medical College Kannur
 Transcortin
Cortisol binding globulin
For cortisol and corticosterone
Synthesised by liver
Increased in pregnancy

Department of Biochemistry
Govt Medical College Kannur
 Haptoglobulin(hp)

• Plasma glycoprotein that binds

extracorpuscular haemoglobulin
• Prevents loss of free haemoglobulin
• Synthesised in liver
• Low levels indicates hemolysis

Department of Biochemistry
Govt Medical College Kannur
 Transferrin
• Glycoprotein ; synthesized in
liver
• For iron transportation
• Conserves iron by preventing
iron loss in urine

Department of Biochemistry
Govt Medical College Kannur
 Hemopexin

For free heme

Prevents loss of heme

Department of Biochemistry
Govt Medical College Kannur
 ACUTE PHASE PROTEIN

• Level of certain proteins in

blood may rise to 50 -1000
folds in many inflammatory
and neoplastic conditions
• Play a role in body ‘s
response to inflammation
Department of Biochemistry
Govt Medical College Kannur
CRP(C-Reactive protein)
• Reacts with C-polysaccharide
capsule of pneumococci
• Beta globulin
• Synthesised in liver
• Stimulate compliment activity and
macrophage phagocytosis
• Predictive value for Myocardial
infarction
Department of Biochemistry
Govt Medical College Kannur
 Ceruloplasmin
• Synthesized by hepatic parenchymal cells and
small portion by lymphocytes and macrophages
• Carries 90% copper from the body
• Also called ferroxidase
• 6-8 copper atoms per molecule
• Cp is not a transport protein ( Albumin is carrier
for Copper)

Department of Biochemistry
Govt Medical College Kannur
• Normal Cp level
Males 22 – 40 mg /dl
Females 25 – 60 mg/dl

in Wilson’s disease ,malnutrition

,nephrosis & cirrhosis
A/C Hepatitis ,cirrhosis ,pregnancy
,estrogen & OCP therapy etc
Ferroxidase activity

Cp-Cu++ Cp-Cu+

Fe2+
Fe3+
 Wilson’s disease
• Autosomal recessive disorder.
• Mutation in gene encoding copper
binding ATPase
• Defect in the incorporation of Cu++in to
newly synthesized apoceruloplasmin.
• Ceruloplasmin in blood drastically
reduced
• Impaired ability of liver to excrete
Cu++in to bile
 Wilson disease progresses with copper
accumulation

damage causes the liver

copper builds up in the liver to release the copper
and injures liver tissue directly
into the bloodstream

copper buildup
Neurological symptoms, leads to damage
liver failure, and death. in the kidneys,
brain, and eyes
 Clinical features

Total body retention of copper is

increased particularly in organs like
liver, brain, kidney & cornea
• Liver cirrhosis
• Brain lenticular degeneration
• Kidney renal tubular damage
• Cornea Kayser Fleischer ring
Investigations
• Urinary excretion of copper is increased
• Serum ceruloplasmin is decreased
• Liver copper is increased

Treatment
Low copper intake
• D penicillamine - excretion of copper
• Zinc - copper absorption
 Alfa-1 antitrypsin(AAT)

• Alpha antiprotease or protease

inhibitor- inhibits all serine
protease (SERPINS)
• Synthesised in liver

Department of Biochemistry
Govt Medical College Kannur
 ALPHA-1 ANTI TRYPSIN(AAT)

AAT deficiency causes Emphysema

- commonest inborn errors

AAT activity reduced in Nephrotic

syndrome : AAT lost in urine

Department of Biochemistry Govt Medical

College Kannur
Department of Biochemistry Govt Medical
College Kannur
 Alpha fetoprotein
• α-1 globulin
• Synthesized by fetal liver
• Present in maternal serum during
pregnancy
 high value – neural tube defect
 low value - chromosomal disorders
• Tumor marker in liver cancer
 Alpha -2 macroglobulin

• Tetrameric proteins
• Synthesised by hepatocytes
and macrophages
• Invivo anticoagulant
• Carrier of many growth factors
• Increased in nephrotic
syndrome Department of Biochemistry Govt Medical
College Kannur
 Negative acute phase
protein
During an inflammatory
response , some proteins are
decreased in blood – negative
acute phase proteins
Egs – albumin,transthyretin, RBP,
transferrin
Department of Biochemistry Govt Medical
College Kannur