PLASMA PROTEINS

The colloid osmotic pressure due to plasma colloids is called the oncotic pressure. It is determined by the number of molecules dissolved in a fluid rather than by the mass of these molecules. Albumin contributes the maximum to oncotic pressure compared to other proteins like globulins and fibrinogen because it has low molecular weight & high concentration.

The colloid osmotic pressure of normal human plasma averages about 28mm Hg. 19mm Hg of this is caused by molecular effects of the dissolved protein and 9mm Hg by the cations held in plasma by the proteins, which is called the Donnan effect.

Ref: Cellular Proteins and Their Fatty Acids in Health and Disease,  Edited By Asim K. Duttaroy, Page 79.

A i.e. Low molecular weight and high blood concentration

Osmotic pressure is determined by the number of particles in solution and not by the mass of the particle, that means 1 gm of a heavy molecular weight protein will contain a lesser no. of particles than 1 gm of a light molecular weight protein, & conse uentiv will have a lesser osmotic pressure

Of the there major types of plasma protein, albumin with minimum molecular weight contributes. max to plasma oncotic pressure.

A i.e. Albumin; B i.e. Globuin; C i.e. Prealbumin

Thyroid hormones in blood is transported combined with plasma proteins. Normally 99.9% of T4 (&T3) in plasma is protein bound. Plasma protein which bind T4 & T3 are:

i)         AlbuminQ

ii)       Thyroxine binding prealbuminQ (TBPA) (new called transthyretin)

iii)      Thyroxine binding globulinQ (TBG): affinity to bind T4 is maximum.

– TransferrinQ [apotrans ferrin 03 -globulin) + Fe]: transport iron to plasmaQ.

–  CeruloplasminQ [Copper binding protein] transport Cu to plasma.

Ans. is ‘b’ i.e., Haptoglobin

Ans. is ‘d’ i.e., Sex steroid hormones do not bind to any protein in plasma

o Acidic drugs mainly bind to albumin and basic drugs to alpha-1 acid glycoprotein. Drugs having high PPB like sulfonamides can displace other drugs bound to same site and may result in toxicity.

Sex steroids bind to steroid hormone binding globulin as well as albumin.

Ans. A i.e. Erythropoietin

Erythropoietin causes formation and release of new RBCs into circulation

Ans. B: Transferrin

Transferrin

• They are iron-binding blood plasma glycoproteins that control the level of free iron in biological fluids.
• In humans, it is encoded by the TF gene.
• Transferrin is a glycoprotein that binds iron very tightly but reversibly.
• Although iron bound to transferrin is less than 0.1% (4 mg) of the total body iron, it is the most important iron pool, with the highest rate of turnover.
• Transferrin has a molecular weight of around 80 kDa and contains 2 specific high-affinity Fe (III) binding sites.
• The affinity of transferrin for Fe (III) is extremely high but decreases progressively with decreasing pH below neutrality.
• When not bound to iron, it is known as “apo-transferrin”

Ferritin

• It is a ubiquitous intracellular protein that stores iron and releases it in a controlled fashion.
• The amount of ferritin stored reflects the amount of iron stored.
• In humans, it acts as a buffer against iron deficiency and iron overload.
• Ferritin is a globular protein complex consisting of 24 protein subunits and is the primary intracellular iron-storage protein in both prokaryotes and eukaryotes, keeping iron in a soluble and non-toxic form.
• Ferritin that is not combined with iron is called apoferritin.

Ans. C: Transferrin

Iron-binding proteins are carrier proteins and metalloproteins which play many important roles in metabolism. They bind Iron and can therefore inhibit microbial growth.

Two iron-binding proteins are lactoferrin and transferrin.

Some of the iron after absorption is stored in ferritin, and the remainder is transported out of the enterocytes by a transporter named ferroportin 1. Hephaestin is associated with ferroportin 1.

Free fatty acids are transported in the blood bound to albumin, a serum protein secreted by the liver. Most other lipids are transported in the blood as part of complex particles called lipoproteins.

Lipoproteins differ in the ratio of protein to lipids, and in the particular apoproteins and lipids that they contain. They are classified based on their density:

• Chylomicron (largest; lowest in density due to high lipid/protein ratio; highest in triacylglycerols as a percentage of weight)
• VLDL (very low-density lipoprotein; 2nd highest in percentage by weight)
• LDL (low-density lipoprotein, highest in cholesteryl esters as the percentage by weight)
• HDL (high-density lipoprotein, highest in density due to high protein/lipid ratio).

Ans. B: Albumin

There are two types of fluids that are used for intravenous drips; crystalloids and colloids.

Crystalloids are aqueous solutions of mineral salts or other water-soluble molecules.

Colloids contain larger insoluble molecules, such as albumin; blood itself is a colloid.

Colloids preserve a high colloid osmotic pressure in the blood, while, on the other hand, this parameter is decreased by crystalloids due to hemodilution.

Another difference is that crystalloids generally are much cheaper than colloids.

The most commonly used crystalloid fluid is normal saline, a solution of sodium chloride at 0.9% concentration, which is close to the concentration in the blood (isotonic).

Ringer’s lactate or Ringer’s acetate is another isotonic solution often used for large-volume fluid replacement.

A solution of dextrose 5% in water, sometimes called D5W, is often used instead if the patient is at risk for having low blood sugar or high sodium.

Ans. is ‘a’ i.e., Ceruloplasmin

Copper is mainly transported as ceruloplasmin :‑

• Normally, 40% to 60% of daily ingested copper (2 to 5 mg) is absorbed in the stomach & duodenum. o It is transported to the liver loosely complexed with albumin.
• Free copper dissociates and is taken up into hepatocytes, where it is incorporated into an a_,-globulin synthesized in the endoplasmic reticulum to form ceruloplasmin (a copper-containing metallothionein) and resecreted into plasma.
• Ceruloplasmin accounts for 90% to 95% of plasma copper, although its biologic role is unknown, since the six to seven atoms of copper in each protein molecule are not readily exchangeable.
• Circulating ceruloplasmin is desialylated as part of normal plasma protein aging
• Desialylated ceruloplasmin is endocytosed by the liver, degraded within lysosomes, and its copper is excreted into bile. This degradation/excretion pathway is the primary route for copper elimination.
• Estimated total body copper is only 50 to 150 mg.

Ans. is ‘c’ i.e., Globulin

Most of the circulating thyroid, hormones are protein bound, leaving only 0.02% T₄ and about 0.2% T₃ unbound or free.

There are three hormone binding plasma proteins, i.e., thyroxine binding globulin (major thyroid hormone binding protein), thyroxine binding albumin and thyroxine binding prealbumin.

Thyroid binding globulin level is raised in pregnancy and by drugs estrogens, methadone, heroin, tranquilizers, clofibrate.

TBG decreases by glucocorticoid, androgen, danazol, asparginase (cancer chemotherapy) and nephrotic syndrome.

Ans. is ‘ d’ i.e., Thyroxine

• Albumin is involved in transport of several substances because of its predominantly polar nature. 
• Nearly 40% of plasma calcium is bound-up with albumin.
• Other substances which are Bound-up and/or tranported by albumin are :‑

1. Free fatty acids
2. Bilirubin
3. Steroids
4. Many nonpolar drugs

Coming back to question

• Thyroxine also binds to albumin, but it is not the major transport protein for thyroxin. Most of the thyroxine is transported by globulin.
• Thyroxine binding plasma proteins are :-

1. Thyroxine binding globulin Major thyroid hormone binding protein
2. Thyroxine binding albumin
3. Thyroxine binding pre-albumin

• Thus, among the given options, thyroxine is the best answer.

Ans. is ‘c’ i.e., Albumin 

• Many natural substances circulate around the body partly free in plasma water and partly bound to plasma proteins, e.g. cortisol, thyroxine.
• Similarly drugs circulate in protein bound and free states, and the significance is that the free fraction is pharmacologically active whereas the protein bound component is a reservoir of drug that is inactive because of this binding.
• Acidic drugs generally bind to plasma albumin.
• Basic drugs bind to a, acid glycoprotein.
• Binding to albumin is quantitatively more important.