Tay–Sachs disease belongs to the latter. Other
Other lipid storage disorders that generally are not classified as sphingolipidoses include fucosidosis, Schindler disease, and Wolman disease. Genetics
Lipid storage diseases can be inherited two ways:
Autosomal recessive inheritance occurs when both parents carry and pass on a copy of the faulty gene, but neither parent show signs and symptoms of the condition and is not affected by the disorder. Each child born to these parents have a 25 percent chance of inheriting both copies of the defective gene, a 50 percent chance of being a carrier, and a 25 percent chance of not inheriting either copy of the defective gene. Children of either gender may be affected by an autosomal recessive this pattern of inheritance.X-linked recessive (or sex linked) inheritance occurs when the mother carries the affected gene on the X chromosome that has determined the childs gender and passes it to her son. Sons of carriers have a 50 percent chance of inheriting the disorder. Daughters have a 50 percent chance of inheriting the X-linked chromosome, but usually are not severely affected by the disorder. Affected men do not pass the disorder to their sons, but their daughters will be carriers for the disorder. Diagnosis
Diagnosis of the lipid storage disorders can be achieved through the use of several tests. These tests include clinical examination, biopsy, genetic testing, molecular analysis of cells or tissues, and enzyme assays. Certain forms of this disease also can be diagnosed through urine testing, which detects the stored material.
The enzymes OxyA, OxyB, OxyC, and OxyD are cytochrome P450 enzymes. OxyB catalyzes oxidative cross-linking between residues 4 and 6, OxyA between residues 2 and 4, and OxyC between residues 5 and 7. This cross-linking occurs while the heptapeptide is covalently bound to the PCP domain of the 7th NRPS module. These P450s are recruited by the X domain present in the 7th NRPS module, which is unique to glycopeptide antibiotic biosynthesis. The cross-linked heptapeptide is then released by the action of the TE domain, and methyltransferase Vmt then N-methylates the terminal leucine residue. GtfE then joins D-glucose to the phenolic oxygen of residue 4, followed by the addition of vancosamine catalyzed by GtfD. Some of the glycosyltransferases capable of glycosylating vancomycin and related nonribosomal peptides display notable permissivity and have been employed for generating libraries of differentially glycosylated analogs through a process known as glycorandomization. Total synthesis
Both the vancomycin aglycone and the complete vancomycin molecule have been targets successfully reached by total synthesis. The target was first achieved by David Evans in October 1998, KC Nicolaou in December 1998, Dale Boger in 1999, and has recently been more selectively synthesized again by Dale Boger in 2020. Pharmacology and chemistry
Vancomycin is a branched tricyclic glycosylated nonribosomal peptide produced by the Actinomycetota species Amycolatopsis orientalis (formerly designated Nocardia orientalis). Vancomycin exhibits atropisomerism — it has multiple chemically distinct rotamers owing to the rotational restriction of some of the bonds. The form present in the drug is the thermodynamically more stable conformer.