Biochemical Markers

Biochemical markers can be used for the identification of various diseases and conditions, such as infections or bone degradation.
Biochemical Markers
Samuel Antonio Sánchez Amador

Written and verified by el biólogo Samuel Antonio Sánchez Amador.

Last update: 28 May, 2023

Biochemical markers are defined as a character or a gene that, thanks to various linkage characteristics, can indicate the presence of another. For example, protein A would be a marker of greater height in the individual —characteristic B— if both were correlated. A marker possessed the property that A necessarily implies B.

So, almost any morphological character or underlying process that encodes it can be considered a marker, from protein or DNA to something as specific as the size of a leaf. A marker is always correlated with another character of interest.

Immerse yourself with us in this world of genetics and chemistry, as we enter the world of biochemical markers and their peculiarities. In addition to their characteristics, we’ll also show various clinical applications of these useful molecules.

Biochemical markers: The correlation of life

In the first place, we must define —albeit superficially— the types of markers present in the field of research. The popular science magazine Ciencia y el Hombre shows us some simple examples.

Morphological markers

The phenotype is defined as the genetic expression of the individual, which is determined by the environment in which it lives and other factors. Therefore, if a gene codes for leaf color as dark green, this character will show different ranges depending on environmental conditions and the health of the plant.

We’ve thrown out this general definition because morphological markers are based on the variety of phenotypes present in nature. They’re easy to identify, such as color, size, shape, or height. Due to its simplicity, this type of marker was the first to be used by humans.

For example, if eye color were linked to the EYCL1 gene, this hue would be a morphological marker for the gene in question. However, these types of markers are limited. In the case presented, there are at least four other genes that explain ocular coloration. Therefore, morphotype-to-character correlation is usually not so easy to find.

Genetic markers.
Markers are useful in the detection of diseases and in the monitoring of disorders.

Genetic markers

A genetic marker is a segment of DNA with a known location on a chromosome. It should be noted that its genetic inheritance – how it’s distributed from parents to children – can be traced, and, furthermore, that it can be a specific gene or a non-coding DNA sequence or one with no known function.

Associations such as the National Human Genome Research Institute (NIH) emphasize that these markers are essential. For example, they can help link an inherited disease to the responsible gene. Genetic markers are used to trace the inheritance of a nearby gene that hasn’t yet been identified, but whose approximate location is known.

Biochemical markers

Last —but not least— we have biochemical markers. These include various types of proteins, among which we find the following:

  • Isozymes: Enzymes that differ in amino acid sequence, but have the same function
  • Allozymes: Alternative forms of an enzyme encoded by different alleles in the same gene
  • Non-enzymatic proteins

We’re talking about the first generation of markers. The proteins are encoded by the individual’s genome, so their correlation is more reliable than, for example, morphological markers.

Although gene expression is also influenced by the environment (epigenetics), the protein-to-gene ratio is reliable. Therefore, biochemical markers can be used as diagnostic support in multiple diseases.

How are biochemical markers obtained?

The answer is simple: By electrophoresis. This technique is based on the use of an electric field that separates the different proteins and enzymes according to their size or electrical properties.

We can summarize this process as a sort of horse race. The protein extract of the sample to be analyzed is placed in a support well, which finds its starting line on an agarose gel. The application of electrical charge is the starting signal, as the different proteins will advance through the gel according to their properties.

Without going into details that are too technical, we can say that, once the process is finished and after applying a series of stains, various bands made up of the different proteins are observed along the gel or paper. Portals such as Científica Senna show different types of protein electrophoresis.

The electrophoretic distances of the isoenzymes are the result of the differences in the DNA sequences that encode them.

A practical example

The United States National Library of Medicine shows us a practical example of this process. This is the case with the urine protein electrophoresis (EPPO) test. For this, a urine sample from the patient is required under aseptic conditions.

This sample is placed on special paper or in the aforementioned gel and an electric current is applied. Therefore, bands form along the paper depending on the different amounts of protein in the urine. This makes it possible to identify, for example, high globulin or albumin values.

The advantages and disadvantages of the technique

This methodology has its pros and cons, although the benefits balance the scales in your favor. Some of the advantages of biochemical markers are as follows:

  1. It’s a relatively cheap and accessible technique.
  2. It’s not destructive, as few amounts of the sample are required to perform electrophoresis.
  3. The genetic control of most isoenzymes is well known. Therefore, associating the electrophoresis gel bands with genetic inferences is a straightforward task.
  4. Isozymes are free of certain genetic processes that make it difficult to describe the process of inheritance.

Despite all these positive characteristics, biochemical markers also report certain problems:

  1. They present technical issues at times.
  2. They only represent a small fraction of the individual’s genetic content. That is, they don’t cover the entire genome.
  3. Interpretation of the data can be made difficult by certain processes. For example, the same isoenzyme can present a different form in the tissue of a tree leaf or its seed, despite being the same individual.

Clinical uses of biochemical markers

Now that we’ve determined what a biochemical marker is, how it’s obtained, and its advantages and disadvantages, it’s time to move onto more tangible terms. Here are some practical examples of the use of biochemical markers in modern medical processes.

Biochemical markers in osteoporosis

The journal Clinical Rheumatology shows us a clear example of the use of these markers in degenerative processes of bone tissue. Biochemical markers can be used to measure the products generated during the formation or degradation of bone matrix. For example, alkaline phosphatase —a hydrolase enzyme— or osteocalcin.

On the other hand, tartrate-resistant acid phosphatase (TRAP) or urinary calcium excretion are markers of bone tissue destruction. The concentrations of these compounds make it possible to distinguish groups of patients according to the bone situation they’re experiencing. Although they can’t be considered a unique diagnostic method, they provide very valuable information.

Biochemical markers in metabolic syndromes

On the other hand, the journal Endocrinology and Nutrition shows us how these markers can provide relevant information on various metabolic processes.

For example, protein, genetic, and lipid oxidation markers serve to quantify the level of an individual’s total antioxidant status. Therefore, the concentration of substances such as isoprostanes can become a chemical bioindicator of a metabolic disorder in the patient.

Of course, summarizing the diagnostic effect of these compounds in a few lines is complex, to say the least. These biochemical markers are also used for the diagnosis of periodontal diseases, for the prevention of cardiovascular disorders, and as parameters for the inference of many other diseases.

By means of electrophoresis, the markers can be separated in the laboratory to carry out their detection and analysis.

What marker to use?

As you’ve been able to see above, each marker has a specific moment and usefulness. A morphological marker can be useful for general studies. For example, seed size has been correlated with individual survival and growth in pine trees. Therefore, by measuring the seed in question, it’s possible to predict what the quality of life of the adult tree will be like.

At the same time, genetic markers stand out when it comes to establishing inheritance relationships or genetic mapping of species of living beings. For example, there are sections of DNA called microsatellites that are inherited from parent to child. This allows for pedigrees and family trees of animals in their natural environment.

Ultimately —and as we’ve said previously— biochemical markers are useful in supporting the diagnosis of various diseases. This helps to know the state of the patient throughout a clinical picture and infer possible diseases.

A question of genes

Throughout the above article, we’ve reviewed the types of markers, their specific qualities, and their uses in modern medicine. In summary, all this terminological conglomerate is rooted in a key concept: Genes represent the variety of life.

Biochemical markers open the door to a more exact knowledge of various diseases, how they’ll develop, and the possible patterns on which they’re inherited. Even so, the cited studies agree on a specific point: For now, these molecules should be used as an accessory point of view and shouldn’t be the central basis of a diagnosis.

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