The possibility of replacing threonine by nitrogen-free analogues in a diet of patients with diabetic nephropathy: a biochemical aspect
Andrey V. Malinovskiy
HERALD of North-Western State Medical University named after I.I. Mechnikov ›› 2022, Vol. 14 ›› Issue (3) : 5 -12.
The possibility of replacing threonine by nitrogen-free analogues in a diet of patients with diabetic nephropathy: a biochemical aspect
There is a well established theory that an essential amino acid of threonine is incapable of transamination. According to this theory, in a diet of patients who suffer from nephropathy, including diabetic threonine, is not replaced by its ketoanalogue. However, transamination of threonine, in the human organism in particular, has been discovered by a number of researchers. This suggests that there is a possibility of replacing threonine by its nitrogen-free analogues in nutrition of patients with nephropathy. At the same time nitrogen-free analogues of all amino acids can be subject to oxidative decomposition subsequently not only up to the finishing products, but they can also form glucose or ketone bodies, or both. Depending on this, amino acids are divided into glucogenic only, ketogenic only or both at the same time.
With reference to diabetes this becomes especially important as introduction of glucogenic amino acids and their nitrogen-free analogues has a positive effect, whereas that of ketogenic amino acids and their nitrogen-free analogues is inadmissible. This is caused by the fact that before being transformed into glucose, glucogenic amino acids are transformed into one or another component of Krebs cycle or into the pyruvic acid which is in balance with the components which stimulates oxydation of acetyl coenzyme A and, therefore, ketone bodies.
Ketose with reference to diabetes can be caused by two reasons. While the main source of energy of a healthy person is carbohydrate, in case with diabetes fats perform the function — being oxydized intensively, they form a great number of ketone bodies. The second reason is a decrease in the formation of oxaloacetic acid (Krebs cycle catalyst) from pyruvic acid due to a decrease in the formation of the latter from glucose and an increase in the use of the components of the Krebs cycle for gluconeogenesis.
Ketose causes a sharp shift of pH value to more acidity as a result of accumulation of the acetoacetic acid and the β-hydroxybutyric acid in blood and narcotic actions of the third ketonic body — acetone. The reason for lethal outcome with reference to diabetes is diabetic coma caused by a sharp shift of pH value to more acidity, which disturbs the work of the ferments. Threonine has a strong glucogenic effect in the complete absence of a ketogenic effect on the human body. In this respect, nitrogen-free analogues of threonine do not differ from it.
glucogenic action / ketogenic action / transamination / threonine
| [1] |
Bellizzi V, Calella P, Hernández JN, et al. Safety and effectiveness of low-protein diet supplemented with ketoacids in diabetic patients with chronic kidney diseas. BMC Nephrol. 2018;19(1):110. DOI: 10.1186/s12882-018-0914-5 |
| [2] |
Bellizzi V., Calella P., Hernández J.N. et al. Safety and effectiveness of low-protein diet supplemented with ketoacids in diabetic patients with chronic kidney diseas // BMC Nephrol. 2018. Vol. 19, No. 1. P. 110. DOI: 10.1186/s12882-018-0914-5 |
| [3] |
Elliott DF, Neuberger A. The irreversibility of the deamination of threonine in the rabbit and rat. Biochem J. 1950;46(2):207–210. DOI: 10.1042/bj0460207 |
| [4] |
Elliott D.F., Neuberger A. The irreversibility of the deamination of threonine in the rabbit and rat // Biochem. J. 1950. Vol. 46, No. 2. P. 207–210. DOI: 10.1042/bj0460207 |
| [5] |
Koppe L, Cassani de Oliveira M, Fouque D. Ketoacid analogues supplementation in chronic kidney disease and future perspectives. Nutrients. 2019;11(9):2071. DOI: 10.3390/nu11092071 |
| [6] |
Koppe L., Cassani de Oliveira M., Fouque D. Ketoacid analogues supplementation in chronic kidney disease and future perspectives // Nutrients. 2019. Vol. 11, No. 9. P. 2071. DOI: 10.3390/nu11092071 |
| [7] |
Meltzer HL, Sprinson DE. The synthesis of 4-C14, N15-L- threonine and a study of its metabolism. J Biol Chem.1952;197(1):461–473. |
| [8] |
Meltzer H.L., Sprinson D.E. The synthesis of 4-C14, N15-L-threonine and a study of its metabolism // J. Biol. Chem. 1952. Vol. 197, No. 1. P. 461–473. |
| [9] |
Noguchi T, Okuno E, Kido R. Idenity of isoenzyme 1 of histidine-pyruvate aminotransferase with serine-pyruvate aminotransferase. Biochem J. 1976;159(3):607–613. DOI: 10.1042/bj1590607 |
| [10] |
Noguchi T., Okuno E., Kido R. Idenity of isoenzyme 1 of histidine-pyruvate aminotransferase with serine-pyruvate aminotransferase // Biochem. J. 1976. Vol. 159, No. 3. P. 607–613. DOI: 10.1042/bj1590607 |
| [11] |
Ishikawa T, Okuno E, Tsujimoto M, et al. Kynurenine-pyruvate aminotransferase in rat kidney and brain. Adv Exp Med Biol. 1991;294:567–572. DOI: 10.1007/978-1-4684-5952-4_68 |
| [12] |
Ishikawa T., Okuno E., Tsujimoto M. et al. Kynurenine-pyruvate aminotransferase in rat kidney and brain // Adv. Exp. Med. Biol. 1991. Vol. 294. P. 567–572. DOI: 10.1007/978-1-4684-5952-4_68 |
| [13] |
Hsiehs B, Tolbert NE. Glyoxylate aminotransferase in peroxisomes from rat liver and kidney. J Biol Chem. 1976;251(14):4408–4415. |
| [14] |
Hsiehs B., Tolbert N.E. Glyoxylate aminotransferase in peroxisomes from rat liver and kidney // J. Biol. Chem. 1976. Vol. 251, No. 14. P. 4408–4415. |
| [15] |
Okuno E, Minatogawa Y, Nakamura M, et al. Crystallization and characterization of human liver kynurenine-glyoxylate aminotransferase. Identity with alanine-glyoxylate aminotransferase and serine-pyruvate aminotransferase. Biochem J. 1980;189(3):581–590. DOI: 10.1042/bj1890581 |
| [16] |
Okuno E., Minatogawa Y., Nakamura M. et al. Crystallization and characterization of human liver kynurenine-glyoxylate aminotransferase. Identity with alanine-glyoxylate aminotransferase and serine-pyruvate aminotransferase // Biochem. J. 1980. Vol. 189, No. 3. P. 581–590. DOI: 10.1042/bj1890581 |
| [17] |
Okuno E, Tsujimoto M, Nakamura M, Kido R. 2-Aminoadipate-2-oxoglutarate aminotransferase isoenzymes in human liver:a plausible physiological role in lysine and tryptophan metabolism. Enzyme Protein. 1993;47(3):136–148. DOI: 10.1159/000468669 |
| [18] |
Okuno E., Tsujimoto M., Nakamura M., Kido R. 2-Aminoadipate-2-oxoglutarate aminotransferase isoenzymes in human liver:a plausible physiological role in lysine and tryptophan metabolism // Enzyme Protein. 1993. Vol. 47, No. 3. P. 136–148. DOI: 10.1159/000468669 |
| [19] |
Malinovsky AV. Does threonine possess any ketogenic action? Problems of Biological, Medical and Pharmaceutical Chemistry. 2020;23(6):34–39. (In Russ.). DOI: 10.29296/25877313-2020-06-06 |
| [20] |
Малиновский А.В. Обладает ли треонин кетогенным действием? // Вопросы биологической, медицинской и фармацевтической химии. 2020. Т. 23, № 6. С. 34–39. DOI: 10.29296/25877313-2020-06-06 |
| [21] |
Bird MI, Nunn PB. Metabolic homeostasis of L-threonine in the normally fed rat. Biochem J. 1983;214(3):687–693. DOI: 10.1042/bj2140687 |
| [22] |
Bird M.I., Nunn P.B. Metabolic homeostasis of L-threonine in the normally fed rat // Biochem. J. 1983. Vol. 214, No. 3. P. 687–693. DOI: 10.1042/bj2140687 |
| [23] |
Laver WG, Neuberger A, Scott JJ. α-Amino-β-keto-acids. Part II. Rates of decarboxylation of the free acids and the behaviorer of derivates on titration. Journal of the Chemical Society. 1959:1483–1491. |
| [24] |
Laver W.G., Neuberger A., Scott JJ. α-Amino-β-keto-acids. Part II. Rates of decarboxylation of the free acids and the behaviorer of derivates on titration // Journal of the Chemical Society. 1959. P. 1483–1491. |
| [25] |
Pagani R, Guerranti R, Leoncini R, Marinello E. Activation and inhibition of rat liver L-threonine dehydrogenase. Ital J Biochem. 1990;39(2):108. |
| [26] |
Pagani R., Guerranti R., Leoncini R., Marinello E. Activation and inhibition of rat liver L-threonine dehydrogenase // Ital. J. Biochem. 1990. Vol. 39, No. 2. P. 108. |
| [27] |
Pagani R, Guerranti R, Righi S, et al. Identification of a mitochondrial inhibitor of rat liver L-threonine dehydrogenase. Biochem Biophys Actа. 1995;244(1):49–52. DOI: 10.1016/0304-4165(94)00192-z |
| [28] |
Pagani R., Guerranti R., Righi S. et al.Identification of a mitochondrial inhibitor of rat liver L-threonine dehydrogenase // Biochem. Biophys. Actа. 1995. Vol. 244, No. 1. P. 49–52. DOI: 10.1016/0304-4165(94)00192-z |
| [29] |
Guerranti R, Pagani R, Neri S, et al. Inhibition and regulation of rat liver L-threonine dehydrogenase. By different fatty acids and their derivates. Biochem Biophys Acta. 2001;1568(1):45–52. DOI: 10.1016/s0304-4165(01)00197-0 |
| [30] |
Guerranti R., Pagani R., Neri S. et al. Inhibition and regulation of rat liver L-threonine dehydrogenase. By different fatty acids and their derivates // Biochem. Biophys. Acta. 2001. Vol. 1568, No. 1. P. 45–52. DOI: 10.1016/s0304-4165(01)00197-0 |
| [31] |
Malinovsky AV. Is threonine an essential amino acid? Preventive and Clinical Medicine. 2011;(4(41)):116–119. (In Russ.) |
| [32] |
Малиновский А.В. Является ли треонин незаменимой аминокислотой? // Профилактическая и клиническая медицина. 2011. № 4(41). С. 116–119. |
| [33] |
Malinovsky AV. Reason for indispensability of threonine in humans and other mammals in comparative aspect. Biochemistry (Moscow). 2017;82(9):1055–1060. |
| [34] |
Малиновский А.В. Причины незаменимости треонина у человека и млекопитающих в сравнительном аспекте // Биохимия. 2017. Т. 82, № 9. С. 1354–1360. |
| [35] |
Malinovsky AV. Why threonine is an essential amino acid in mammals and birds: studies at the enzyme level. Biochemistry (Moscow). 2018;83(7):795–799. DOI: 10.1134/S0006297918070039 |
| [36] |
Малиновский А.В. Проблемы незаменимости треонина у млекопитающих и птиц на ферментном уровне // Биохимия. 2018. Т. 83, № 7. С. 981–986. DOI: 10.1134/S0320972518070035 |
| [37] |
Malinovsky AV. Reasoning of generation of threonine indispensability in evolutionary aspect. Tsitologiya. 2019;61(7):521–528. (In Russ.). DOI: 10.1134/S0041377119070058 |
| [38] |
Малиновский А.В. Причины возникновения незаменимости треонина в свете эволюции // Цитология. 2019. Т. 61, № 7. С. 521–528. DOI: 10.1134/S0041377119070058 |
| [39] |
Beryozov TT. Exchange of amino acids of normal tissues and that of malignant tumours. Moscow: Medicine; 1969. (In Russ.) |
| [40] |
Березов Т.Т. Обмен аминокислот нормальных тканей и злокачественных опухолей. Москва: Медицина, 1969. |
| [41] |
Beryozov TT, Korovkin BF. Biological Chemistry. Moscow: Medicine; 2004. (In Russ.) |
| [42] |
Березов Т.Т., Коровкин Б.Ф. Биологическая химия. Москва: Медицина, 2004. |
| [43] |
Barrett G. Chemistry and biochemistry of the amino acids. UK, London; New York Chapman and Hall; 2012. |
| [44] |
Barrett G. Chemistry and biochemistry of the amino acids. UK, London; New York: Chapman and Hall, 2012. |
| [45] |
Growdon JH, Nader TM, Schoenfeld J, Wurtman RJ. L-threonine in the treatment of spasticity. Cln Neuropharmacol. 1991;14(5):403−412. DOI: 10.1097/00002826-199110000-00003 |
| [46] |
Growdon J.H., Nader T.M., Schoenfeld J., Wurtman R.J. L-threonine in the treatment of spasticity // Cln. Neuropharmacol. 1991. Vol. 14, No. 5. P. 403−412. DOI: 10.1097/00002826-199110000-00003 |
| [47] |
Lee A, Patterson V. Double-blind study of L-threonine in patients with spinal spasticity. Acta Neurol Scand. 1993;88(5):334−338. DOI: 10.1111/j.1600-0404.1993.tb05353.x |
| [48] |
Lee A., Patterson V. Double-blind study of L-threonine in patients with spinal spasticity // Acta Neurol. Scand. 1993. Vol. 88, No. 5. P. 334−338. DOI: 10.1111/j.1600-0404.1993.tb05353.x |
| [49] |
Edgar AJ. The human L-threonine-3-dehydrogenase gene is an expressed pseudogene. BMC Genet. 2002;3:18. DOI: 10.1186/1471-2156-3-18 |
| [50] |
Edgar A.J. The human L-threonine-3-dehydrogenase gene is an expressed pseudogene // BMC Genet. 2002. Vol. 3. P. 18. DOI: 10.1186/1471-2156-3-18 |
| [51] |
Han C, Cai T, Tagle DA, et al. Substrate specificity and structure of human aminoadipate aminotransferase/kynurenine aminotransferase II. Biosci Rep. 2008;28(4):205–215. DOI: 10.1042/BSR20080085 |
| [52] |
Han C., Cai T., Tagle D.A. et al. Substrate specificity and structure of human aminoadipate aminotransferase/kynurenine aminotransferase II // Biosci. Rep. 2008. Vol. 28, No. 4. P. 205–215. DOI: 10.1042/BSR20080085 |
| [53] |
Shah AP, Kalantar-Zadeh K, Kopple JD. Is there a role for ketoacid supplements in the management of CKD? Am J Kidney Dis. 2015;65(5):659–673. DOI: 10.1053/j.ajkd.2014.09.029 |
| [54] |
Shah A.P., Kalantar-Zadeh K., Kopple J.D. Is there a role for ketoacid supplements in the management of CKD? // Am. J. Kidney Dis. 2015. Vol. 65, No. 5. Р. 659–673. DOI: 10.1053/j.ajkd.2014.09.029 |
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