Introduction
A 29-year-old Jewish male has developed a large kidney stone. He has had nothing to eat for the past month but jello and chicken. Feeding on chicken and jello which are rich in glycine is dangerous to the body since they are converted into oxalate stone. It has been shown that diet that is deficient of vitamin B6 but rich in glycine, is dangerous since it leads to the formation of kidney stones (Knight, Jiang, Assimos, & Holmes, 2006). Hence, the 29 years Jewish is highly prevalent since he feeds on diet only rich in glycine. The jello and chicken diet that the 29 years old Jewish male feeds on is high on glycine which when metabolized in absence of vitamin B6 produces oxalate which in excess develops into severe hypocituria or hyperoxaluria.
The Chemistry of Kidney Stones
The metabolism is every food type in the body undergoes unique pathways to produce specific end products under suitable conditions. The food breakdown process is aided by enzymes that are specific for the metabolism of certain food types in the body. Proteins are broken down by specific enzymes and so are other food types. Moreover, the metabolism of food is done in various parts of the body. Below is a chain of reactions that take place when collagen jello which is rich in glycine undergoes a series of processes in the body upon consumption. The breakdown process determines the type of end products to be formed as shown below, however, the pathways that lead to the glyoxalate synthesis are poorly defined.
As shown in the flow diagram above, jello is digested into glycine, which is then oxidized to glycine imine which is further hydrolyzed into glyoxylate and ammonia and later oxalate. While that is a longer path, a shorter route involves digestion into glycine to glyoxylate a precursor of oxalate without undergoing glycine imine stage.
Metabolism of Glyoxylate
In human beings, the source of glyoxylate is glycolate, glycine, hydroxyproline, and gloxal. Glyoxylate acts as a metabolism intermediary and is a two-carbon keto -acid. Through dehydrogenases and oxidases process, it is converted into oxalate. On the other hand, glycine, plays may roles in the body such as acting as the precursor of purines, 1-carbon units and proteins (Lamers, 2009).
The breakdown of glyoxylate is aided by the glyoxylate aminotransferase. According to Pey, Albert and Salido (2013), the coenzyme alanine-glyoxylate aminotransferase is responsible for catalyzing the transmission between glycine and pyruvate to glyoxylate and L-alanine.
When the enzyme alanine-glyoxalate aminotransferase (AGT) is absent during the metabolism process, the person develops primary hyperoxaluria type 1 (Pey, Albert & Salido, 2013).
When a person takes a diet rich in glyoxylate in the absence of vitamin B6, there is a likelihood of developing severe hypocituria or hyperoxaluria (Nishijima, 2006). Oxalate is a toxin in the body since it precipitates as tissue-damaging calcium oxalate, hence it has to be excreted through urine. In this regard, the detoxification process of glyoxalate in the human body is very essential. A normal oxalate excretion level is below 0.5 mmoL/1.73 m2, hence any level above 5 mmoL is too high.
It has been established through research that vitamin B6 is essential in the metabolism of glyoxylate (Nishijima, 2006). Vitamin B 6 which is otherwise known as pyridoxal 5'-phosphate (PLP) is used as a cofactor in the metabolism of glyoxalate. Nishijima (2006) examined the role played by vitamin B 6 in the metabolism of glyoxalate and hepatic alanine in rats. The study divided male rats into a vitamin B6 free diet and glyoxalate water group, control group, glyoxalate water group, and vitamin B-6 deficient diet. All the groups were fed with a special diet that was deficient of vitamin B-6 and a drinking water for a 4 weeks duration after which the levels of hepatic AGT mRNA were determined. The study found a high oxalate/creatinine ratio in three groups, and high glycolate/creatinine ratio in the groups without vitamin B-6 although the control group had low levels. However, the study found that the glycine/creatinine ratio was low in the two groups without vitamin B-6. Conversely, the levels of hepatic AGT mRNA was low in groups without vitamin B-6 but higher in the control group and glycolate water group. From these results, it can be deduced that glyoxalate metabolism requires vitamin B-6 as a coenzyme of AGT. At high levels of glyoxylate intake, the vitamin B-6 is highly needed. The deficiency of vitamin B-6 leads to severe hyperoxaluria. These findings have been supported by Runjan and Gershoff (1964) who established that deficiency of vitamin B-6 in rats, monkeys, and cats are associated with an increment in the excretion of endogenous urinary oxalate. The authors posited that the high levels of oxalate n urine are as a result of alterations that vitamin B-6 causes during the metabolism of various compounds in the body.
Due to the presence of glyoxalate reductase activity in the kidney, the glyoxalate can be converted back to glycine. However, the kidney has AGT2 activity whose affinity for glyoxalate is lower compared to AGT1 (Knight et al., 2006). For kidney to facilitate such conversion, AGT1 is a requirement since it has a higher affinity. Besides, since the conversion rate is very slow, the conversion of glycine into glyoxalate outweighs the reverse conversion. Hence, its lack hinders the conversion of glyoxalate to glycine and this facilitates more formation of oxalate hence escalating the kidney problem.
Conclusion
In conclusion, high intake of jello and animal proteins such as chicken meat predisposes the body into the development of oxalate stones in the kidney. The metabolism process of glycine takes place in presence of alanine-glyoxalate aminotransferase and vitamin B 6 commonly known as pyridoxal 5' -phosphate (PLP). PLP acts as the cofactor while the alanine-glyoxalate aminotransferase (AGT) acts as the enzyme. The enzyme catalyzes the transmission between glycine and pyruvate to glyoxylate and L-alanine. Hence its absence during metabolism leads to the development of primary hyperoxaluria type 1. In the absence of vitamin B-6, the process of converting glycine to glyoxalate becomes favorable forming oxalate and consequently kidney stones. Although the kidney can convert the glyoxylate to glycine, kidney contains AGT2 activity whose affinity for glyoxalate is lower compared to AGT1. In this regard, the conversion rate is very low and the glycine to glyoxalate outweighs the kidney reverse process. Taking diet rich in glycine, deficient of vitamin B-6 and without AGT leads to the formation of oxalate and this escalates into severe hypocituria or hyperoxaluria.
References
Knight, J., Easter, L. H., Neiberg, R., Assimos, D. G., & Holmes, R. P. (2009). Increased protein intake on controlled oxalate diets does not increase urinary oxalate excretion. Urological Research, 37(2), 63-68. DOI:10.1007/s00240-009-0170-z
Lamers, Y., Williamson, J., Ralat, M., Quinlivan, E., Gilbert, L., Keeling ...& Gregory, J. (2009). Moderate Dietary Vitamin B-6 Restriction Raises Plasma Glycine and Cystathionine Concentrations While Minimally Affecting the Rates of Glycine Turnover and Glycine Cleavage in Healthy Men and Women. The Journal of Nutrition, 139(3), 452-460. DOI: 10.3945/jn.108.099184
Nishijima et al. (2006). Effect of vitamin B6 deficiency on glyoxylate metabolism in rats with or without glyoxylate overload, Biomed Res, 27(3):93-8. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/16847354
Pey, A. L., Albert, A., & Salido, E. (2013). Protein homeostasis defects of alanine-glyoxylate aminotransferase: new therapeutic strategies in primary hyperoxaluria type I. BioMed research international, 2013, 687658. DOI:10.1155/2013/687658
Runyan, T., & Gershoff, S. (1965). The Effect of Vitamin B, Deficiency in Rats on the Metabolism of Oxalic Acid Precursors. The Journal of Biological Chemistry, 240(5). Retrieved from https://pdfs.semanticscholar.org/6afb/6767595dc7f482fbd1767d70b137dce00d82.pdf?_ga=2.257343371.1438465190.1567082852-1871163874.1566280296
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