Browsing Pathways

Malonyl-CoA decarboxylase deficiency, also called malonic aciduria, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder caused by a defective MLYCD gene. The MLYCD gene codes for the protein malonyl-CoA decarboxylase which regulates the creation and degradation of fatty acids. This disorder is characterized by a large accumulation of fatty acid byproducts in the tissues. Symptoms of the disorder include delayed development, hypotonia, seizures, vomiting, diarrhea and cardiomyopathy. Treatment with L-carnitine is very effective, as it encourages beta-oxidation of fatty acids. Less than 30 cases globally have ever been reported, making this disorder extremely rare.

Malonyl-CoA decarboxylase deficiency, also called malonic aciduria, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder caused by a defective MLYCD gene. The MLYCD gene codes for the protein malonyl-CoA decarboxylase which regulates the creation and degradation of fatty acids. This disorder is characterized by a large accumulation of fatty acid byproducts in the tissues. Symptoms of the disorder include delayed development, hypotonia, seizures, vomiting, diarrhea and cardiomyopathy. Treatment with L-carnitine is very effective, as it encourages beta-oxidation of fatty acids. Less than 30 cases globally have ever been reported, making this disorder extremely rare.

Malonyl CoA decarboxylase deficiency, also claled MCD deficiency, is a rare inborn error of fatty acid metabolism and autosomal-recessive metabolic disorder, which is caused by a defective mitochondrial malonyl CoA decarboxylase due to reduced activity. Mitochondrial malonyl CoA decarboxylase catalyzes the conversion of intramitochondrial malonyl CoA to acetyl CoA, which is a key product that involve in many biochemical reactions. This disorder is characterized by a large accumulation of methylmalonic acid in the mitochondrial. Symptoms of the disorder include hypotonia (i.e. weak muscle tone), hypoglycemia (i.e. low blood sugar), diarrhea, seizures and vomiting. The Malonyl CoA decarboxylase deficiency is an extremely rare genetic disease happened in early childhood, which only less than 30 cases have been reported. There is currently no cure for Malonyl CoA decarboxylase deficiency, treatment involves managing the disorder's symptoms.

Malonyl CoA decarboxylase deficiency, also claled MCD deficiency, is a rare inborn error of fatty acid metabolism and autosomal-recessive metabolic disorder, which is caused by a defective mitochondrial malonyl CoA decarboxylase due to reduced activity. Mitochondrial malonyl CoA decarboxylase catalyzes the conversion of intramitochondrial malonyl CoA to acetyl CoA, which is a key product that involve in many biochemical reactions. This disorder is characterized by a large accumulation of methylmalonic acid in the mitochondrial. Symptoms of the disorder include hypotonia (i.e. weak muscle tone), hypoglycemia (i.e. low blood sugar), diarrhea, seizures and vomiting. The Malonyl CoA decarboxylase deficiency is an extremely rare genetic disease happened in early childhood, which only less than 30 cases have been reported. There is currently no cure for Malonyl CoA decarboxylase deficiency, treatment involves managing the disorder's symptoms.

Maple syrup urine disease, also called BCKD deficiency, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder caused by a defective BCKDHA, BKCDHB or DBT gene. These genes code for a protein which is vital in the breakdown of amino acids, specifically the amino acids leucine, isoleucine and valine. This disorder is characterized by a large accumulation of these amino acids in the body. Symptoms of the disorder include a distinct maple syrup smell of the urine, vomiting, lethargy, abnormal movements and delayed development. Treatment includes long-term dietary management which aims to restrict the consumption of branched-chain amino acids. It is estimated that maple syrup urine disorder affects 1 in 185,000 infants globally. This number increases significantly when looking specifically at Old World Order Mennonites, where the prevalence is 1 in 380 infants.

Maple syrup urine disease, also called BCKD deficiency, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder caused by a defective BCKDHA, BKCDHB or DBT gene. These genes code for a protein which is vital in the breakdown of amino acids, specifically the amino acids leucine, isoleucine and valine. This disorder is characterized by a large accumulation of these amino acids in the body. Symptoms of the disorder include a distinct maple syrup smell of the urine, vomiting, lethargy, abnormal movements and delayed development. Treatment includes long-term dietary management which aims to restrict the consumption of branched-chain amino acids. It is estimated that maple syrup urine disorder affects 1 in 185,000 infants globally. This number increases significantly when looking specifically at Old World Order Mennonites, where the prevalence is 1 in 380 infants.

Medium-chain acyl-CoA dehydrogenase deficiency, which is also known as MCADD, is a rare inherited inborn error of metabolism (IEM) medium-chain fatty acid metabolism. The estimated birth prevalence of MCADD is between 1 in 4 900 to 1 in 27 000 in Caucasian populations and is highest in Northern European individuals. Worldwide birth prevalence is 1 in 14 600. MCADD is an autosomal recessive disorder associated with a mutation in the enzyme medium-chain acyl-CoA dehydrogenase (MCAD). MCAD is an enzyme that catalyzes the initial step in each cycle of medium-chain fatty acid beta-oxidation in the mitochondria of cells. MCAD’s action results in the introduction of a trans-double-bond between C2 and C3 of the acyl-CoA thioester substrate. Defects in MCAD leads to the accumulation of medium-chain fatty acids in the blood, lowering the blood's pH and causing acidosis. Likewise, individuals with MCADD have difficulty metabolizing fats. As a result, MCADD is characterized by intolerance to prolonged fasting, recurrent episodes of hypoglycemic coma with medium-chain aciduria, impaired ketogenesis, and low plasma and tissue carnitine levels. Intolerance to fasting and hypoglycemia result from the inability to gain energy and make sugar from fat stores, which is how most excess energy from food is stored. It is rare for the signs and symptoms of MCADD to first appear during adulthood. Typically, they manifest during infancy or early childhood and can include lethargy, hypoglycemia, and vomiting. MCAD-deficient individuals are at risk for breathing difficulties, liver problems, seizures, brain damage, coma, and sudden death. Fasting or illnesses (e.g. viral infections) can trigger related problems. Infants and young children with MCADD need to eat frequently to prevent hypoglycemia or a metabolic crisis. MCADD is occasionally mistaken for Reye syndrome, a severe disorder that may manifest in children during apparent recovery from viral infections such as flu or chickenpox. The majority of Reye syndrome cases are associated with aspirin use during these viral infections.

Medium-chain acyl-CoA dehydrogenase deficiency, which is also known as MCADD, is a rare inherited inborn error of metabolism (IEM) medium-chain fatty acid metabolism. The estimated birth prevalence of MCADD is between 1 in 4 900 to 1 in 27 000 in Caucasian populations and is highest in Northern European individuals. Worldwide birth prevalence is 1 in 14 600. MCADD is an autosomal recessive disorder associated with a mutation in the enzyme medium-chain acyl-CoA dehydrogenase (MCAD). MCAD is an enzyme that catalyzes the initial step in each cycle of medium-chain fatty acid beta-oxidation in the mitochondria of cells. MCAD’s action results in the introduction of a trans-double-bond between C2 and C3 of the acyl-CoA thioester substrate. Defects in MCAD leads to the accumulation of medium-chain fatty acids in the blood, lowering the blood's pH and causing acidosis. Likewise, individuals with MCADD have difficulty metabolizing fats. As a result, MCADD is characterized by intolerance to prolonged fasting, recurrent episodes of hypoglycemic coma with medium-chain aciduria, impaired ketogenesis, and low plasma and tissue carnitine levels. Intolerance to fasting and hypoglycemia result from the inability to gain energy and make sugar from fat stores, which is how most excess energy from food is stored. It is rare for the signs and symptoms of MCADD to first appear during adulthood. Typically, they manifest during infancy or early childhood and can include lethargy, hypoglycemia, and vomiting. MCAD-deficient individuals are at risk for breathing difficulties, liver problems, seizures, brain damage, coma, and sudden death. Fasting or illnesses (e.g. viral infections) can trigger related problems. Infants and young children with MCADD need to eat frequently to prevent hypoglycemia or a metabolic crisis. MCADD is occasionally mistaken for Reye syndrome, a severe disorder that may manifest in children during apparent recovery from viral infections such as flu or chickenpox. The majority of Reye syndrome cases are associated with aspirin use during these viral infections.

2-Aminobenzoic acid, also known as anthranilic acid or O-aminobenzoate, belongs to the class of organic compounds known as aminobenzoic acids. These are benzoic acids containing an amine group attached to the benzene moiety. Within humans, 2-aminobenzoic acid participates in a number of enzymatic reactions. In particular, 2-aminobenzoic acid and formic acid can be biosynthesized from formylanthranilic acid through its interaction with the enzyme kynurenine formamidase. In addition, 2-aminobenzoic acid and L-alanine can be biosynthesized from L-kynurenine through its interaction with the enzyme kynureninase. It is a substrate of enzyme 2-Aminobenzoic acid hydroxylase in benzoate degradation via hydroxylation pathway (KEGG). In humans, 2-aminobenzoic acid is involved in tryptophan metabolism. Outside of the human body, 2-Aminobenzoic acid has been detected, but not quantified in several different foods, such as mamey sapotes, prairie turnips, rowals, natal plums, and hyacinth beans. This could make 2-aminobenzoic acid a potential biomarker for the consumption of these foods. 2-Aminobenzoic acid is a is a tryptophan-derived uremic toxin with multidirectional properties that can affect the hemostatic system. Uremic syndrome may affect any part of the body and can cause nausea, vomiting, loss of appetite, and weight loss. Chronic exposure of uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease. It can also cause changes in mental status, such as confusion, reduced awareness, agitation, psychosis, seizures, and coma. Kynureninase catalyzes the cleavage of L-kynurenine (L-Kyn) and L-3-hydroxykynurenine (L-3OHKyn) into anthranilic acid (AA) (which is also known as 2-Aminobenzoic acid) and 3-hydroxyanthranilic acid (3-OHAA), respectively. Has a preference for the L-3-hydroxy form. Also has cysteine-conjugate-beta-lyase activity.

Kynurenine is a uremic toxin that is produced when a person has uremia or renal failure. Kynurenine is naturally synthesized in the body from tryptophan. Tryptophan is consumed through foods such as milk, eggs, chicken, turkey, and oats. Tryptophan is then transported from the small intestine into the blood by an amino acid transport. In the blood it travels to the liver and is transported into a hepatocyte by an amino acid transporter. The kynurenine pathway becomes dysregulated, potentially through over-stimulation by interferon gamma (IFNG). This hyperstimulation leads to large reductions in tryptophan levels as the indole dioxygenase (IDO) enzyme becomes more active. IDO activation results in the generation (from tryptophan) of large amounts of kynurenine (and its other metabolites) through a self-stimulating autocrine process. Kynurenine binds to the arylhydrocarbon receptor (AhR) found in most immune cells [5-7]. In addition to increased kynurenine production via IDO mediated synthesis, hyopalbuminemia can also lead to the release of bound kynurenine (and other immunosuppressive LysoPCs) into the bloodstream to fuel this kynurenine-mediated process. Regardless of the source of kynurenine, the kynurenine-bound AhR will migrate to the nucleus to bind to NF-kB which leads to more production of the IDO enzyme, which leads to more production of kynureneine and more loss of tryptophan. Kynurenine then enters the blood via a liver organic anion transporter such as solute carrier family 22 member 9. Kynurenine is shown to activate aryl hydrocarbon receptors that can lead to renal impairment, apoptosis, and kynurenine has also been found to disrupt the electron transport chain and oxidative phosphorylation causing muscle atrophy.