Phenylalanine is an essential α-amino acid with the formula C
9H
11NO
2. It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine. This essential amino acid is classified as neutral, and nonpolar because of the inert and hydrophobic nature of the benzyl side chain. The L-isomer is used to biochemically form proteins coded for by DNA. Phenylalanine is a precursor for tyrosine, the monoamine neurotransmitters dopamine, norepinephrine (noradrenaline), epinephrine (adrenaline), and the skin pigment melanin. It is encoded by the codons UUU and UUC.
A gluten-free casein-free diet, also known as a gluten-free dairy-free diet, is a diet that does not include gluten, and casein. Despite an absence of scientific evidence, there have been advocates for the use of this diet as a treatment for autism and related conditions.
Gliadorphin is an opioid peptide that is formed during digestion of the gliadin component of the gluten protein. It is usually broken down into amino acids by digestion enzymes. It has been hypothesized that children with autism have abnormal leakage from the gut of this compound. This is partly the basis for the gluten-free, casein-free diet. Abnormally high levels of gliadorphin have been found in the urine of autistic children via mass spectrometry testing.
Alkylresorcinols, also known as resorcinolic lipids, are phenolic lipids composed of long aliphatic chains and resorcinol-type phenolic rings.
Hartnup disease is an autosomal recessive metabolic disorder affecting the absorption of nonpolar amino acids. Niacin is a precursor to nicotinamide, a necessary component of NAD+.
Many causes of autism have been proposed, but understanding of the theory of causation of autism and the other autism spectrum disorders (ASD) is incomplete. Attempts have been made to incorporate the known genetic and environmental causes into a comprehensive causative framework. ASD is a complex developmental condition marked by persistent challenges to social interaction, speech and nonverbal communication, and restricted/repetitive behaviors and its phenotypes vary significantly.
5-Hydroxyindoleacetic acid (5-HIAA) is the main metabolite of serotonin. In chemical analysis of urine samples, 5-HIAA is used to determine serotonin levels in the body.
Trace amines are an endogenous group of trace amine-associated receptor 1 (TAAR1) agonists – and hence, monoaminergic neuromodulators – that are structurally and metabolically related to classical monoamine neurotransmitters. Compared to the classical monoamines, they are present in trace concentrations. They are distributed heterogeneously throughout the mammalian brain and peripheral nervous tissues and exhibit high rates of metabolism. Although they can be synthesized within parent monoamine neurotransmitter systems, there is evidence that suggests that some of them may comprise their own independent neurotransmitter systems.
Tryptophan hydroxylase (TPH) is an enzyme (EC 1.14.16.4) involved in the synthesis of the neurotransmitter serotonin. Tyrosine hydroxylase, phenylalanine hydroxylase, and tryptophan hydroxylase together constitute the family of biopterin-dependent aromatic amino acid hydroxylases. TPH catalyzes the following chemical reaction
An aromatic amino acid is an amino acid that includes an aromatic ring.
Phenylacetylglutamine is a product formed by the conjugation of phenylacetate and glutamine. It is a common metabolite that occurs naturally in human urine.
The kynurenine pathway is a metabolic pathway leading to the production of nicotinamide adenine dinucleotide (NAD+). Metabolites involved in the kynurenine pathway include tryptophan, kynurenine, kynurenic acid, xanthurenic acid, quinolinic acid, and 3-hydroxykynurenine. The kynurenine pathway is responsible for total catabolization of tryptophan about 95%. Disruption in the pathway is associated with certain genetic and psychiatric disorders.
3,5-Dihydroxybenzoic acid is a dihydroxybenzoic acid. It is a colorless solid.
3,5-Dihydroxyphenylpropionoic acid is a metabolite of alkylresorcinols, first identified in human urine and can be quantified in urine and plasma, and may be an alternative, equivalent biomarker of whole grain wheat intake.
Auto-brewery syndrome(ABS) is a condition characterized by the fermentation of ingested carbohydrates in the gastrointestinal tract of the body caused by bacteria or fungi. ABS is a rare medical condition in which intoxicating quantities of ethanol are produced through endogenous fermentation within the digestive system. The organisms responsible for ABS include various yeasts and bacteria, including Saccharomyces cerevisiae, S. boulardii, Candida albicans, C. tropicalis, C. krusei, C. glabrata, C. kefyr, C. parapsilosis, Klebsiella pneumoniae, and Enterococcus faecium. These organisms use lactic acid fermentation or mixed acid fermentation pathways to produce an ethanol end product. The ethanol generated from these pathways is absorbed in the small intestine, causing an increase in blood alcohol concentrations that produce the effects of intoxication without the consumption of alcohol.
Paul Shattock is a British autism researcher and scientific consultant to the charity Education and Services for People with Autism, of which he is also the founder. He was formerly the director of the Autism Research Unit at the University of Sunderland. He is well known for his disputed research into dietary therapy and autism, having claimed that autistic children may have a "leaky gut" which allows certain peptides to enter the bloodstream, and claimed that they excrete unusually high levels thereof. As a result of this speculation, he has promoted the use of a gluten-free, casein-free diet to ameliorate the symptoms of autism, a theory he developed along with Kalle Reichelt. In addition, he has claimed that a protein found in milk may play a role in the etiology of autism. He is also the former president of the World Autism Organization.
The opioid excess theory is a theory which postulates that autism is the result of a metabolic disorder in which opioid peptides produced through metabolism of gluten and casein pass through an abnormally permeable intestinal membrane and then proceed to exert an effect on neurotransmission through binding with opioid receptors. It is believed by advocates of this hypothesis that autistic children are unusually sensitive to gluten, which results in small bowel inflammation in these children, which in turn allows these opioid peptides to enter the brain.
Urolithin A is a metabolite compound resulting from the transformation of ellagitannins by the gut bacteria. It belongs to the class of organic compounds known as benzo-coumarins or dibenzo-α-pyrones. Its precursors – ellagic acids and ellagitannins – are ubiquitous in nature, including edible plants, such as pomegranates, strawberries, raspberries, and walnuts. Since the 2000s, urolithin A has been the subject of preliminary studies regarding its possible biological effects.
3-Indolepropionic acid (IPA), or indole-3-propionic acid, is a potent neuroprotective antioxidant, plant auxin, and natural product in humans that is being studied for therapeutic use in Alzheimer's disease. It is endogenously produced by human microbiota and has only been detected in vivo when the species Clostridium sporogenes is present in the gastrointestinal tract. As of April 2016, C. sporogenes, which uses tryptophan to synthesize IPA, is the only species of bacteria known to synthesize IPA in vivo at levels which are subsequently detectable in the blood plasma of the host.
Indoxyl sulfate, also known as 3-indoxylsulfate and 3-indoxylsulfuric acid, is a metabolite of dietary L-tryptophan that acts as a cardiotoxin and uremic toxin. High concentrations of indoxyl sulfate in blood plasma are known to be associated with the development and progression of chronic kidney disease and vascular disease in humans. As a uremic toxin, it stimulates glomerular sclerosis and renal interstitial fibrosis.
