Материалы II студенческой межфакультетсткой конференции первокурсников по биоорганической химии


Purine Frieda Tangi Silvanus, group 9. Scientific adviser is Tishakova Tatyana



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  • HISTINDINE

Purine

Frieda Tangi Silvanus, group 9. Scientific adviser is Tishakova Tatyana.


Heterocyclic compound form the largest group of organic compounds and many have important biological properties. The main heteroatom that occurs in heterocyclic compounds is nitrogen, but there are also ring containing oxygen and sulfur. They are classified in accordance with the following features of their skeleton: according to the ring size, according to the number of heteroatoms and their mutual arrangement in ring, according to a degree of saturation of a matter and according to the number of the rings.

A purine is a heterocyclic aromatic organic compound. It consists of a pyrimidine ring fused to an imidazole ring. Purines, which include substituted purines and their tautomers, are the most widely occurring nitrogen-containing heterocycle in nature. Purines and pyrimidines make up the two groups of nitrogenous bases, including the two groups of nucleotide bases. Two of the four deoxyribonucleotides and two of the four ribonucleotides, the respective building-blocks of DNA and RNA, are purines. Apart from the crucial roles of purines (adenine and guanine) in DNA and RNA, purines are also significant components in a number of other important bimolecules, such as ATP, GTP, cyclic AMP, NADH, and coenzyme A. Purine itself has not been found in nature, but it can be produced by synthesis. They may also function directly as neurotransmitters, acting upon purinergic receptors.

A moderate amount of purine is also contained in beef, pork, poultry, other fish and seafood, asparagus, cauliflower, spinach, mushrooms, green peas, lentils, dried peas, beans, oatmeal, wheat bran, wheat germ, and hawthorn.

nicotinic acid


Obioha John Obumneke, group 9. Scientific adviser is Tishakova Tatyana.

Nicotinic has the formula C6H5NO2



Nicotinic acid has profound and unique effects on lipid metabolism and is thus referred to as a ‘broad-spectrum lipid drug' In addition to elevating HDL cholesterol (as well as decreasing both LDL and total cholesterol nicotinic acid also induces a decrease in the concentrations of both ‘very-low-density lipoproteins' (VLDL) and plasma triglyceride (TG); The plasma concentration of lipoprotein Lp(a), which has been suggested to play a role as an independent risk factor for coronary heart disease, is also decreased by nicotinic acid. Soon after the initial discovery of the lipid-modifying effect of high doses of nicotinic acid the water-soluble vitamin nicotinic acid was introduced into clinical therapy as the first lipid-modifying drug. In the Coronary drug project, conducted from 1966 to 1975, nicotinic acid administered as monotherapy at 3gday−1 was shown to lead to an efficient secondary prevention of myocardial infarction A follow-up study of the Coronary Drug project revealed that nicotinic acid also reduced the mortality of patients who had been treated with nicotinic acid (The Stockholm ischaemic heart disease secondary prevention study came to similar findings. With the introduction of cholesterol synthesis inhibitors (statins) in the therapy of hypercholesterolaemia during the late 1980s, interest in the therapeutic potential of nicotinic acid decreased. However, in recent years, several clinical studies have been conducted to test whether nicotinic acid provides a benefit to patients who are receiving treatment with statins but still display low HDL cholesterol levels. Both the HDL Atherosclerosis Treatment Study and the Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol study indicate that patients with low HDL cholesterol levels benefit from a treatment with nicotinic acid in addition to statins .however, both studies are relatively small and have some limitations, including the lack of an ideally designed control group in HDL Atherosclerosis Treatment Study or the evaluation of the intima-media thickness of the carotid artery as a surrogate parameter for the development of clinically relevant atherosclerosis in the Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol study. In any case, there is good evidence supporting a therapeutic benefit of nicotinic acid and randomized long-term studies to evaluate the effect of nicotinic acid in addition to statins in patients with low HDL cholesterol levels and increased cardiovascular risk have recently been initiated.

HISTINDINE

Okoye Chukwuma I, group 9. Scientific adviser is Tishakova Tatyana.


Histidine is an amino acid which is essential for human body; It has some effects in the tissues as well as the nerve cells and the blood cells.

The imidazole side chain of histidine has a pKa of approximately 6.0. This means that, at physiologically relevant pH values, relatively small shifts in pH will change its average charge. Below a pH of 6, the imidazole ring is mostly protonated as described by the Henderson–Hasselbalch equation. When protonated, the imidazole ring bears two NH bonds and has a positive charge. The positive charge is equally distributed between both nitrogens and can be represented with two equally important resonance structures.

The amino acid is a precursor for histamine and carnosine biosynthesis.



Conversion of histidine to histamine by histidine decarboxylase

Metabolism

The enzyme histidine ammonia-lyasez converts histidine into ammonia and urocanic acid. A deficiency in this enzyme is present in the rare metabolic disorder histidinemia. In Actinobacteria and filamentous fungi, such as Neurospora crassa, histidine can be converted into the antioxidant ergothioneine.



Biochemistry. The imidazole sidechain of histidine is a common coordinating ligand in metalloproteins and is a part of catalytic sites in certain enzymes. In catalytic triads, the basic nitrogen of histidine is used to abstract a proton from serine, threonine, or cysteine to activate it as a nucleophile. In a histidine proton shuttle, histidine is used to quickly shuttle protons. It can do this by abstracting a proton with its basic nitrogen to make a positively charged intermediate and then use another molecule, a buffer, to extract the proton from its acidic nitrogen. In carbonic anhydrases, a histidine proton shuttle is utilized to rapidly shuttle protons away from a zinc-bound water molecule to quickly regenerate the active form of the enzyme. Histidine is also important in hemoglobin in helices E and F. Histidine assists in stabilising oxyhaemoglobin and destabilising CO-bound haemoglobin. As a result, carbon monoxide binding is only 200 times stronger in haemoglobin, compared to 20,000 times stronger in free haem.

Certain amino acids can be converted to intermediates of the TCA cycle. Carbons from four groups of amino acids form the TCA cycle intermediates α-ketoglutarate, succinyl CoA, fumarate, and oxaloacetate. Amino acids that form α-ketoglutarate are glutamate, glutamine, proline, arginine, and histidine. Histidine is converted to formiminoglutamatez (FIGLU). The formimino group is transferred to tetrahydrofolate, and the remaining five carbons form glutamate. Glutamate can be deaminated by glutamate dehydrogenase or transaminated to form α-ketoglutarate.





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