Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.14 (ATP synthase)
 7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have developed a method to deliver hydrophobic proteins such as ATP synthase subunit c and ubiquitin to lysosomes of PMN (polymorphonucleocytes) and fibroblasts. ATP synthase subunit c is stored in the lysosomes of various tissues in late infantile and juvenile forms of neuronal ceriod lipofuscinosis, also called Batten disease (BD). Whether this protein storage is due to an abbreviation in protein or in the lysosomal hydrolases of BD is still not clear. We have sequestered this protein and ubiquitin in the lipid membrane of liposomes. The liposomes coated with autologous heat-aggregated IgG or apolipoprotein E when presented to the PMN and fibroblasts, respectively, accumulated in the lysosomes. Both normal and BD PMN degraded 125I-ubiquitin; the rate of degradation was, however, slower by Batten PMN. These studies indicate that a hydrophobic molecule such as subunit c can be delivered to PMN and fibroblasts, and the sequestered proteins are accessible to lysosomal hydrolases. Therefore, this technique can be used to study the metabolism of highly hydrophobic proteins by lysosomes, especially the biochemical mechanism(s) of subunit c storage in BD.
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PMID:Delivery of liposome-sequestered hydrophobic proteins to lysosomes of normal and Batten disease cells. 903 56

In this chapter, we review how HDL is generated, remodeled, and catabolized in plasma. We describe key features of the proteins that participate in these processes, emphasizing how mutations in apolipoprotein A-I (apoA-I) and the other proteins affect HDL metabolism. The biogenesis of HDL initially requires functional interaction of apoA-I with the ATP-binding cassette transporter A1 (ABCA1) and subsequently interactions of the lipidated apoA-I forms with lecithin/cholesterol acyltransferase (LCAT). Mutations in these proteins either prevent or impair the formation and possibly the functionality of HDL. Remodeling and catabolism of HDL is the result of interactions of HDL with cell receptors and other membrane and plasma proteins including hepatic lipase (HL), endothelial lipase (EL), phospholipid transfer protein (PLTP), cholesteryl ester transfer protein (CETP), apolipoprotein M (apoM), scavenger receptor class B type I (SR-BI), ATP-binding cassette transporter G1 (ABCG1), the F1 subunit of ATPase (Ecto F1-ATPase), and the cubulin/megalin receptor. Similarly to apoA-I, apolipoprotein E and apolipoprotein A-IV were shown to form discrete HDL particles containing these apolipoproteins which may have important but still unexplored functions. Furthermore, several plasma proteins were found associated with HDL and may modulate its biological functions. The effect of these proteins on the functionality of HDL is the topic of ongoing research.
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PMID:HDL biogenesis, remodeling, and catabolism. 2552 86