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Proteins and Proteomics
Published in Firdos Alam Khan, Biotechnology Fundamentals, 2020
Essential amino acids are called essential not because they are more important than the others, but because the body does not synthesize them, making it essential to include them in one’s diet to obtain them. On the other hand, the amino acids arginine, cysteine, glycine, glutamine, histidine, proline, serine, and tyrosine are considered conditionally essential, meaning they are not normally required in the diet but must be supplied exogenously to specific populations who do not synthesize them in adequate amounts. For example, individuals living with phenylketonuria (PKU) disease must keep their intake of phenylalanine extremely low to prevent mental retardation and other metabolic complications. However, phenylalanine is the precursor for tyrosine synthesis. Without phenylalanine, tyrosine cannot be made and so tyrosine becomes essential in the diet of PKU patients.
Proteins and proteomics
Published in Firdos Alam Khan, Biotechnology Fundamentals, 2018
Essential amino acids are called essential not because they are more important than the others, but because the body does not synthesize them, making it essential to include them in one’s diet in order to obtain them. On the other hand, the amino acids arginine, cysteine, glycine, glutamine, histidine, proline, serine, and tyrosine are considered conditionally essential, meaning they are not normally required in the diet, but must be supplied exogenously to specific populations who do not synthesize it in adequate amounts. For example, individuals living with phenylketonuria (PKU) disease must keep their intake of phenylalanine extremely low to prevent mental retardation and other metabolic complications. However, phenylalanine is the precursor for tyrosine synthesis. Without phenylalanine, tyrosine cannot be made and so tyrosine becomes essential in the diet of PKU patients.
Lysosomal Storage Disorders and Enzyme Replacement Therapy
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
To sum up it can be expected that in the future more effective therapies may be available for treating LSDs. In this connection, the enzyme substitution therapy for treating Phenylketonuria (PKU) which has been recently developed by BioMarin Pharmaceutical Inc. should be mentioned. PKU is an autosomal recessive metabolic genetic disorder that results from mutations of the phenylalanine hydroxylase (PAH) gene and is detectable during the first days of life—in the most cases via newborn screening. PHA catalyzes in presence of the cofactor tetrahydrobiopterin the first step in phenylalanine (Phe) metabolism the conversion of this essential amino acid to tyrosine. If left untreated, an accumulation of phenylalanine in the blood and brain may cause behavioral problems, seizures, intellectual disabilities, and irreversible brain damage. Until recently, the only cure is a strict life-long low Phe diet that keeps plasma Phe levels within a range of 2 to 6 mg/dL. On May 6, 2019, BioMarin Pharmaceutical Inc. announced that the European Commission (EC) has granted marketing authorization for Palynziq® (pegvaliase injection). Pegvaliase is approved for PKU patients aged 16 and older who were not able to keep their Phe levels within the recommended range by so far available treatment options. Pegvaliase is the PEGylated recombinant form of phenylalanine ammonia lyase (PAL) from the cyanobacterium Anabaena variabilis that breaks down Phe to trans-cinnamic acid and ammonia. The results of a successful long-term phase 3 clinical trial program (PRISM) have been published by Thomas et al. (2018). BioMarin also expects to submit an investigational new drug application (IND) and/or a clinical trial application (CTA) to the US FDA for its BMN 307 pre-clinical gene therapy product for the treatment of PKU in the second half of 2019. BMN 307 consists among others of a AAV vector, containing the DNA sequence that encodes the functional phenylalanine hydroxylase enzyme, deficient in PKU patients, gene therapies are treated in more detail in Chapter 21. Isabella et al. (2018) developed an alternative therapeutic strategy in that they used synthetic biology to develop a live bacterial therapeutic; they engineered Escherichia coli Nissle (SYNB 1618) to express genes encoding Phe-metabolizing enzymes. Experiments with animals suffering from PKU revealed that this genetically modified probiotic reduced blood Phe concentrations significantly; for similar experiments with the probiotic E. coli Nissle, see Crook et al. (2019).
The possible role of the seaweed Sargassum vulgare as a promising functional food ingredient minimizing aspartame-associated toxicity in rats
Published in International Journal of Environmental Health Research, 2022
Rasha Y. M. Ibrahim, Huda B. I. Hammad, Alaa A. Gaafar, Abdullah A. Saber
Generally, ASP is rapidly and thoroughly metabolized into phenylalanine (50%), aspartic acid (40%), and methanol (10%) by gut esterases and peptidases (Renwick 1985). Phenylalanine has been documented to mediate and/or exacerbate hepatic encephalopathy (Hertelendy et al. 1993), and also can be accumulated in the blood of patients suffering from phenylketonuria (PKU), leading to many health problems such as intellectual disability, seizures, behavioral problems, and mental disorders (Erlandsen et al. 2003). Concerning aspartic acid, it has recently been reported that in high concentrations it acts as a toxin that causes hyperexcitability of neurons, inflicting damage on brain and nerve cells (Rycerz and Jaworska-Adamu 2013). Furthermore, recently published review of Choudhary and Lee (2018) on aspartame metabolites showed that phenylalanine, and its interaction with neurotransmitter, and aspartic acid are fundamentally responsible for altering the brain neurochemical composition. As concerns the third by-product ‘methanol’, it has been documented to have a little bit low toxicity but its produced metabolites ‘formaldehyde and formate’ are considered very toxic (Choudhary and Pretorius 2017). The process of formation of these toxic metabolites is usually accompanied by overproduction of reactive oxygen species (ROS) basically involved in lipid peroxidation (Parthasarathy et al. 2006), and also induce mitochondrial damages and increased microsomal proliferation, leading to cell toxicity (Humphries et al. 2008). Nowadays, limited utilization of synthetic sweeteners, like aspartame, as food additives has highly been recommended due to the diverse allegations related to their oxidative damages and toxicities on different systemic organs, induction of carcinogenicity and foetus malformations, and therefore it is becoming increasingly imperative to find out and exploit other alternative, natural, and safe food additives (Carocho et al. 2014). Additionally, consumers nowadays prefer natural antioxidant food additives than their synthetic analogues due to their health-keeping safety and distinctly intensive roles in disease prevention (Carocho et al. 2015; Nimse and Pal 2015).