Albumin

The structure of albumin. Created by Jawahar Swaminathan and MSD staff at the European Bioinformatics Institute, on Wikipedia.

A physicist working in medicine or biology needs to know some biochemistry. Not much, but enough to understand the structure and function of the most important biological molecules. For instance, one type of molecule that plays a key role in biology is protein. In the first section of Chapter 1 in Intermediate Physics for Medicine and Biology, Russ Hobbie and I write

Proteins are large, complex macromolecules that are vitally important for life. For example, hemoglobin is the protein in red blood cells that binds to and carries oxygen. Hemoglobin is roughly spherical, about 6 nm in diameter.

While hemoglobin is one of the most well-known and important proteins, in this post I’d like to introduce proteins using a different example: albumin. To be precise, human serum albumin. It’s nearly the same size and weight as hemoglobin, and both are found in the blood; hemoglobin in the red blood cells, and albumin in the plasma. Both are globular proteins, meaning they have a roughly spherical shape and are somewhat water soluble. Also, they are both transport proteins: hemoglobin transports oxygen, and albumin transports a variety of molecules including fatty acids and thyroid hormones.

Albumin is mentioned in Chapter 5 of IPMB because it’s the most abundant protein in blood serum, and therefore is important in determining the osmotic pressure of blood. It appears in a terrifying story told in Homework Problem 7 of Chapter 5, dealing with a hospital pharmacy that improperly dilutes a 25% solution of albumin with pure water instead of saline, causing a patient to go into renal failure. It’s also discussed in Chapter 17 of IPMB, where aggregated albumin microspheres are tagged with technetium-99m and used for nuclear medicine imaging.

All proteins are strings, or polymers, of amino acids. There are 21 amino acids commonly found in proteins. Each one has a different side chain. An amino acid is often denoted by a one-letter code. For example, G is glycine, R is arginine, and H is histidine. 

The amino acids. Created by Dancojocari on Wikopedia.

The primary structure of a protein is simply a list of its amino acids in order. Below is the primary structure of albumin.

MKWVTFISLLFLFSSAYSRGVFRRDAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEK

Amino acid polymers often fold into secondary structures. The most common is the alpha helix, held together by hydrogen bonds between hydrogen and nitrogen atoms in nearby amino acids. 

The tertiary structure refers to how the entire amino acid string folds up into its final shape. At the top of this post is a picture of the tertiary structure of albumin. You can see many red alpha helices. 

A mutation is when one or more of the amino acids is replaced by an incorrect one. For instance, in familial dysalbuminemic hyperthyroxinemia, one arginine amino acid is replaced by histidine, which affects how albumin interacts with the thyroid hormones.

Albumin is made in your liver, and a serum albumin blood test can assess liver function. Section 5.4.2 of IPMB discusses some illnesses caused by incorrect osmotic pressure of the blood, which are often associated with abnormal albumin concentrations.

5.4.2 Nephrotic Syndrome, Liver Disease, and Ascites

Patients can develop an abnormally low amount of protein in the blood serum, hypoproteinemia, which reduces the osmotic pressure of the blood. This can happen, for example, in nephrotic syndrome. The nephrons (the basic functioning units in the kidney) become permeable to protein, which is then lost in the urine. The lowering of the osmotic pressure in the blood means that the [driving pressure] rises. Therefore, there is a net movement of water into the interstitial fluid. Edema can result from hypoproteinemia from other causes, such as liver disease and malnutrition.

A patient with liver disease may suffer a collection of fluid in the abdomen. The veins of the abdomen flow through the liver before returning to the heart. This allows nutrients absorbed from the gut to be processed immediately and efficiently by the liver. Liver disease may not only decrease the plasma protein concentration, but the vessels going through the liver may become blocked, thereby raising the capillary pressure throughout the abdomen and especially in the liver. A migration of fluid out of the capillaries results. The surface of the liver “weeps” fluid into the abdomen. The excess abdominal fluid is called ascites.

Albumin is such a common, everyday protein that bovine serum albumin, from cows, is often used in laboratory experiments when a generic protein is required.