Pathways

The shikimate pathway is composed of seven enzymatic reactions in the chloroplast by which phosphoenolpyruvate (PEP) and D-erythrose 4-phosphate (E4P) are converted to chorismate, the common precursor of the aromatic amino acids phenylalanine, tyrosine, and tryptophan as well as other metabolites (e.g. folates). The pathway's absence in animals makes it an attractive target for new antimicrobial agents, anti-parasitic agents, and herbicides. PEP can enter this pathway either from plastidic glycolysis or cytosolic glycolysis. If it enters from the cytosol, then it is pumped into the chloroplast by PEP/phosphate translocator (PPT), an antiporter that exports phosphate into the cytosol simultaneously. Firstly, DAHP synthase, with the help of reduced thioredoxin (TRX) and a divalent cation (e.g. manganese) as cofactors, converts PEP, E4P, and water to 3-deoxy-D-arabino-heptulosonic acid 7-phosphate (DAHP) and phosphate. Secondly, 3-dehydroquinate synthase eliminates a phosphate from DAHP resulting in 3-dehydroquinate. This enzyme requires NAD+ and a divalent cation (e.g. cobalt) as cofactors. The next two reactions are catalyzed by the bifunctional enzyme 3-dehydroquinate dehydratase-shikimate dehydrogenase (DHQ-SDH). In the pathway's third reaction, the enzyme's DHQ domain dehydrates 3-dehydroquinate to 3-dehydroshikimate. In the fourth reaction, the enzyme's SDH domain uses NADPH to reversibly reduce 3-dehydroshikimate to shikimate, releasing NADP in the process. Fifthly, shikimate kinase, which requires a divalent cation (e.g. manganese) as a cofactor, catalyzes the ATP-dependent phosphorylation of shikimate to shikimate 3-phosphate. Sixthly, 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase converts shikimate-3-phosphate and PEP to EPSP, releasing a phosphate in the process. Seventhly, chorismate synthase (CS) catalyzes the 1,4-trans elimination of the phosphate group from EPSP to form chorismate. This enzyme requires reduced flavin mononucleotide (FMNH2) as a cofactor.

3-hydroxyacyl-CoA dehydrogenase deficiency, also known as HADH deficiency or formerly SCHAD deficiency, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder of the mitochondrial beta-oxidation of short chain saturated fatty acid pathway. It is caused by a mutation in the HADH gene which encodes the mitochondrial enzyme hydroxyacyl-coenzyme A dehydrogenase. This enzyme is responsible for the beta-oxidation of 3-hydroxyhexanoyl-CoA and 3-hydroxybutyryl-CoA into 3-oxohexanoyl-CoA and acetoacetyl-CoA respectively. Symptoms of HADH deficiency include hypoglycemia, as well as vomiting, diarrhea and seizures. Treatment with diazoxide, a potassium channel activator, has been effective. It is estimated that HADH deficiency affects less than 1 in 1,000,000 individuals.

3-hydroxyacyl-CoA dehydrogenase deficiency, also known as HADH deficiency or formerly SCHAD deficiency, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder of the mitochondrial beta-oxidation of short chain saturated fatty acid pathway. It is caused by a mutation in the HADH gene which encodes the mitochondrial enzyme hydroxyacyl-coenzyme A dehydrogenase. This enzyme is responsible for the beta-oxidation of 3-hydroxyhexanoyl-CoA and 3-hydroxybutyryl-CoA into 3-oxohexanoyl-CoA and acetoacetyl-CoA respectively. Symptoms of HADH deficiency include hypoglycemia, as well as vomiting, diarrhea and seizures. Treatment with diazoxide, a potassium channel activator, has been effective. It is estimated that HADH deficiency affects less than 1 in 1,000,000 individuals.

3-hydroxyacyl-CoA dehydrogenase deficiency, also known as HADH deficiency or formerly SCHAD deficiency, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder of the mitochondrial beta-oxidation of short chain saturated fatty acid pathway. It is caused by a mutation in the HADH gene which encodes the mitochondrial enzyme hydroxyacyl-coenzyme A dehydrogenase. This enzyme is responsible for the beta-oxidation of 3-hydroxyhexanoyl-CoA and 3-hydroxybutyryl-CoA into 3-oxohexanoyl-CoA and acetoacetyl-CoA respectively. Symptoms of HADH deficiency include hypoglycemia, as well as vomiting, diarrhea and seizures. Treatment with diazoxide, a potassium channel activator, has been effective. It is estimated that HADH deficiency affects less than 1 in 1,000,000 individuals.

3-hydroxyacyl-CoA dehydrogenase deficiency, also known as HADH deficiency or formerly SCHAD deficiency, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder of the mitochondrial beta-oxidation of short chain saturated fatty acid pathway. It is caused by a mutation in the HADH gene which encodes the mitochondrial enzyme hydroxyacyl-coenzyme A dehydrogenase. This enzyme is responsible for the beta-oxidation of 3-hydroxyhexanoyl-CoA and 3-hydroxybutyryl-CoA into 3-oxohexanoyl-CoA and acetoacetyl-CoA respectively. Symptoms of HADH deficiency include hypoglycemia, as well as vomiting, diarrhea and seizures. Treatment with diazoxide, a potassium channel activator, has been effective. It is estimated that HADH deficiency affects less than 1 in 1,000,000 individuals.

Short Chain Acyl CoA Dehydrogenase Deficiency (SCAD Deficiency) is caused by mutation in the gene encoding short-chain acyl-CoA dehydrogenase, an enzyme which normally breaks down short chain fatty acids. SCADD causes accumulation of ammonia in blood; butyrylcarnitine(C4) in plasma; adipic acid, butyrylglycine, ethylmalonic acid; hexanoylglycine and methylsuccinic acid in urine. Symptoms include hypoglycemia, hypotonia, microcephaly, failure to thrive, lactic acidosis, peripheral neuropathy, and vomiting.

Short Chain Acyl CoA Dehydrogenase Deficiency (SCAD Deficiency) is caused by mutation in the gene encoding short-chain acyl-CoA dehydrogenase, an enzyme which normally breaks down short chain fatty acids. SCADD causes accumulation of ammonia in blood; butyrylcarnitine(C4) in plasma; adipic acid, butyrylglycine, ethylmalonic acid; hexanoylglycine and methylsuccinic acid in urine. Symptoms include hypoglycemia, hypotonia, microcephaly, failure to thrive, lactic acidosis, peripheral neuropathy, and vomiting.