There are various aspects of biochemistry which are speculated to be scientifically valid. However, these aspects do not have credible scientific evidence backing them, and are, therefore, known as "hypothetical" types of biochemistry. [1]

This is also known as "Alternative Biochemistry". Alternative Biochemistry includes the study of the alternative building blocks of life, such as non-carbon life, non-water solvents, oxygen alternatives, etc.


Life on earth is made up of proteins, carbohydrates, lipids, nucleic acids, etc. All these biomolecules are made of carbon, hydrogen, and oxygen. One of the biggest speculations regarding extraterrestrial life is that it may be made of elements, other than carbon, hydrogen, and oxygen. However, there is no scientific evidence to back this fact.

Several life forms perform normal biological functions without the presence of carbon, hydrogen, and oxygen. These life forms use arsenic, chlorine, and sulphur as replacement elements.

Water can also be replaced by liquid ammonia or ammonia-water mixture. Other suitable solvents include hydrogen fluoride methanol, hydrogen sulphide, hydrogen chloride, and formamide, which can support alternative forms of biochemical life. However, the presence of these solvents requires a drastically unique and different kind of living system. Such life-forms can exist on outer planets, where the living environment is completely devoid of oxygen and water.

However, it is yet to be scientifically proved whether such alternative life forms amongst plants and higher animals can viably exist on the Earth. This is the basis for the Hypothesis of Alternative Biochemistry.

This article shall focus upon alternative nucleic acids and alternative blood pigments.


• TNA - TNA stands for Threose Nucleic Acid. Deoxyribose and Ribose sugars are replaced by Threose molecules, which have four carbon atoms. TNA does not occur naturally, and is synthesized artificially under controlled situations. TNA was invented by Albert Eschenmoser.

The geometry of TNA is similar to the A-form of DNA. Just like RNA, TNA can also undergo reverse transcription, and form DNA. TNA molecules are resistant to degradation by nucleases. Therefore, these molecules are of great interest in the field of synthetic biology. [3]

• HNA - HNA stands for Hexitol Nucleic Acid, in which Hexoses (six carbon sugars) are present in the form of sugar alcohols known as Hexitols. The most common hexitol present in HNA is a phosphorylated 1',5'-anhydrohexitol residue.

The stability to this molecule is lent by the duplex nature of HNA. [4]

• GNA - GNA stands for Glycol Nucleic Acid. This is the simplest nucleic acid. In the nucleic acid backbone, sugar molecule is replaced by glycol residue (containing three carbon atoms). This is an analogue of 2,3-dihydroxypropylnucleoside.

Watson-Crick base pairing exists in GNA, and this base pairing is stronger and much more stable than in DNA and RNA. This is because a much higher temperature is required to break the duplex GNA strand, as compared to a duplex strand of DNA and/or RNA. [5]

• PNA - PNA stands for Peptide Nucleic Acid. Peptides have great binding strength. Therefore, it is not necessary to create long chains of PNA molecules. PNAs cannot be recognized by nucleases and/or proteases, and they can survive enzyme degradation. PNA residues also exhibit stability over a wide range of pH values.

The basic unit of a PNA molecule is a chain of N-(2-aminoethyl)-glycine units linked to each other by peptide bonds. The purine and pyrimidine bases are linked together by a methylene bridge and a carbonyl group.

PNA does not occur naturally but has been found to be produced in cyanobacteria. The lack of a phosphate group ensures that the binding between a PNA and DNA residue is much stronger than the binding between two DNA residues. [6]

• LNA - LNA stands for Locked Nucleic Acid. This is a modified form of RNA in which the ribose moiety is "locked" due to the formation of an extra bridge that connects the 2' oxygen atom with the 4' carbon atom. This "locked" formation does not occur naturally, but is chemically synthesized.

LNA oligonucleotides comprise of a mixture of LNA residues alongwith DNA and/or RNA residues. Each time a monomer of LNA binds to a complementary DNA or RNA moiety, the Tm of LNA increases by 2-8oC, thus lending greater stability to the structure. Therefore, LNA residues are used for increasing the specificity and sensitivity of DNA microarrays, FISH probes, quantitative PCR probes, and other molecular biology techniques. [7]

• CeNA - CeNA stands for Cyclohexene Nucleic Acid. CeNA contains a cyclohexene ring instead of the normal ?-D-2'-deoxyribose. When CeNA residues are incorporated in a DNA and/or RNA chain, the stability of the chain is increased.

The purpose of creating CeNA was initially to serve as potential mimics for natural nucleic acids, and later for siRNA applications. CeNA shows greater flexibility with regards to the C2-C3 bonding due to the ability of the cyclohexenyl residue to adapt to various types of conformations. [8]

• ANA - ANA stands for Arabino Nucleic Acid. Ribonucleosides undergo epimerization, and yield arabinonucleosides. The conformation of ANA is similar to that of DNA. ANA has an extremely high binding capacity to its target molecules.

ANA is resistant to the action of nucleases, and therefore, various types of biological environments are stabilized in the presence of ANA. [9]


• Hemocyanin - Proteins that transport oxygen in the bodies of invertebrate animals are called hemocyanins. These are metalloproteins having a copper residue, in which two copper atoms bind reversibly to a single oxygen molecule (O2). Hemocyanins are not bound to the blood cells, but are free-floating in the hemolymph. Upon undergoing oxygenation, colourless Cu(I) is transformed into blue-coloured Cu(II). [10]

• Chlorocruorin - This is a hemeprotein present in the blood plasma of annelids. It has an extremely weak affinity for oxygen. Chlorocruorin is a dichromatic compound - it is green in colour in the diluted form, and red in colour in the concentrated form. [11]

• Hemerythrin - Oligomeric protein responsible for oxygen transport in marine invertebrates. It is colourless in the deoxygenated form, and violet-pink in colour in the oxygenated form. Hemerythrin does not contain an iron prosthetic group. [12]

• Pinnaglobin - A brown respiratory pigment present in the blood of molluscs of the genus Pinna. This is similar to hemocyanin, but contains manganese instead of copper. [13]

• Coboglobin - This is an artificially synthesized blood pigment. Coboglobin is a metalloprotein similar to hemoglobin and myoglobin, but contains cobalt as the prosthetic group, instead of iron. Coboglobin binds reversibly to molecular oxygen. Coboglobin is amber-yellow in colour in the deoxygenated form, and colourless in the oxygenated form. [14]

• Vaska's complex - Vaska's complex contains a central Iridium atom which is bound to two mutually trans-triphenylphosphine ligands, carbon monoxide, and a chloride ion. It is a bright yellow crystalline solid, and can undergo oxidative addition, so as to reversibly bind to oxygen. [15]


[1] http://en.wikipedia.org/wiki/Hypothetical_types_of_biochemistry
[2] http://www.dailygalaxy.com/my_weblog/2012/08/extraterrestrial-life-alternative-biochemistries--1.html
[3] http://en.wikipedia.org/wiki/Threose_nucleic_acid
[4] http://www.ncbi.nlm.nih.gov/pubmed/11829600
[5] http://en.wikipedia.org/wiki/Glycol_nucleic_acid
[6] http://www.ncbi.nlm.nih.gov/pubmed/10834926
[7] http://www.crchudequebec.ulaval.ca/ronyweb/DOWNLOADS/Locked_Nucleic_Acids.pdf
[8] http://www.google.co.in/patents/WO2001049687A2?cl=en
[9] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3467067/
[10] http://en.wikipedia.org/wiki/Hemocyanin
[11] http://en.wikipedia.org/wiki/Chlorocruorin
[12] http://en.wikipedia.org/wiki/Hemerythrin
[13] http://www.merriam-webster.com/dictionary/pinnaglobin
[14] http://www.pnas.org/content/67/2/637.full.pdf
[15] http://en.wikipedia.org/wiki/Vaska's_complex

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