Within the field of

biochemistry Biochemistry, or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology, a ...

, 4-amino-5-hydroxymethyl-2-methylpyrimidine (HMP) also known as toxopyrimidine together with its mono

phosphate Phosphates are the naturally occurring form of the element phosphorus. In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthop ...

(HMP-P) and

pyrophosphate In chemistry, pyrophosphates are phosphorus oxyanions that contain two phosphorus atoms in a linkage. A number of pyrophosphate salts exist, such as disodium pyrophosphate () and tetrasodium pyrophosphate (), among others. Often pyrophosphates a ...

(HMP-PP) esters are

biogenetic A biogenic substance is a product made by or of life forms. While the term originally was specific to metabolite compounds that had toxic effects on other organisms, it has developed to encompass any constituents, secretions, and metabolites of p ...

precursors to the important biochemical cofactor

thiamine pyrophosphate Thiamine pyrophosphate (TPP or ThPP), or thiamine diphosphate (ThDP), or cocarboxylase is a thiamine (vitamin B1) derivative which is produced by the enzyme thiamine diphosphokinase. Thiamine pyrophosphate is a cofactor that is present in all liv ...

(TPP), a derivative of

thiamine Thiamine, also known as thiamin and vitamin B1, is a vitamin – an Nutrient#Micronutrients, essential micronutrient for humans and animals. It is found in food and commercially synthesized to be a dietary supplement or medication. Phosp ...

(vitamin B₁). HMP, HMP-P and HMP-PP are found along with thiamine forms in a wide variety of living organisms. Thiamine in various salt, formulation and biological matrix forms are used to supplement human and animal diets because these organisms lack the capability to produce it. Methodologies are being sought for biotechnology-based production of thiamine forms and for increasing thiamine content in food sources.

TPP biogenesis

In microorganisms and plants TPP results from coupling of

pyrimidine Pyrimidine (; ) is an aromatic, heterocyclic, organic compound similar to pyridine (). One of the three diazines (six-membered heterocyclics with two nitrogen atoms in the ring), it has nitrogen atoms at positions 1 and 3 in the ring. The oth ...

fragment HMP-PP with

thiazole Thiazole (), or 1,3-thiazole, is a 5-membered heterocyclic compound that contains both sulfur and nitrogen. The term 'thiazole' also refers to a large family of derivatives. Thiazole itself is a pale yellow liquid with a pyridine-like odor and the ...

fragment HET-P to give thiamine monophosphate, followed by conversion to the pyrophosphate. Biogenesis of HMP-P and HET-P vary with types of organism.

HMP-P biogenesis

In bacteria, HMP-P arises by conversion of the purine biosynthetic precursor 5-aminoimidazole ribotide (AIR) through the action of enzymes such as phosphomethylpyrimidine synthase, a member of the

radical SAM Radical SAM enzymes belong to a superfamily of enzymes that use an iron-sulfur cluster (4Fe-4S) to reductively cleave S-Adenosyl methionine, ''S''-adenosyl-L-methionine (SAM) to generate a radical (chemistry), radical, usually a 5′-deoxyadenosyl ...

superfamily. Studies using isotopically labelled AIR have shown which atoms carry into the product. Mechanisms by which this occurs are not yet known with certainty. In yeasts, HMP-P is derived from metabolites of

histidine Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an Amine, α-amino group (which is in the protonated –NH3+ form under Physiological condition, biological conditions), a carboxylic ...

and

pyridoxine Pyridoxine (PN) is a form of vitamin B6 found commonly in food and used as a dietary supplement. As a supplement it is used to treat and prevent pyridoxine deficiency, sideroblastic anaemia, pyridoxine-dependent epilepsy, certain metaboli ...

. Some of these transformations appear to be catalyzed by radical SAM enzymes. Isotopically labelled precursors have been used to investigate this biogenesis. Mechanisms of the transformations are unknown. In ''

Salmonella ''Salmonella'' is a genus of bacillus (shape), rod-shaped, (bacillus) Gram-negative bacteria of the family Enterobacteriaceae. The two known species of ''Salmonella'' are ''Salmonella enterica'' and ''Salmonella bongori''. ''S. enterica'' ...

'', HMP-P can be derived independently of purine biogenesis when AICAR is available. In algae, thiamine forms and precursors are scavenged by uptake from water of exogenous products from other organisms. In higher plants, thiamine biogenesis resembles that of bacteria. In some circumstances, thiamine forms and precursors may be obtained through symbiotic relationships with microorganisms in the soil. Genes relevant for transformations in the biogenesis of HMP-P, HET-P, and TPP have been identified in various organisms and some of the proteins resulting from their expression have been characterized. Biosynthesis of TPP is feedback inhibited through actions of a riboswitch. Research is ongoing towards understanding biochemistry involved and towards facilitating technologies of socioeconomic value for supply of thiamine in various forms.

Related technologies

Commercially available salts

chloride and thiamine nitrate are produced at scales of thousands of tons annually by chemistry-based manufacturing processes in Europe and Asia. These salts are supplied for formulations for supplementation of human diet and as feed additives for cattle, swine, poultry and fish. Research for potential biotechnology-based production of thiamine has resulted in patent applications claiming fermentation using recombinant microorganisms modified to deregulate feedback inhibition and allow release of thiamine forms to the media as demonstrated at small scale. Thiamine forms and their bio-precursors are produced at very large scale in biological matrices such as yeast, grains, plants and meats widely consumed as food and feed. Research into genetic modification of plants. has led to higher levels of thiamine in foodstuffs, such as rice. Use of thiamine forms and their bio-precursors by various means such as seed coating or soil and foliar fertilization to improve plant growth and properties are being investigated.

References

{{DEFAULTSORT:Amino-5-hydroxymethyl-2-methylpyrimidine, 4- Biochemistry Phosphates Thiamine Pyrimidines