Endocytosis metabolic activity

Some inhibitors for this pathway, often described in the literature, do not directly affect the clathrin pathway but rather affect features involved with other pathways. For example, the acidification of endosomes is employed by the other types of endocytosis as well—therefore, these inhibitors are less specific and are described in the section Intracellular Trafficking The same occurs with dynamin dependence or metabolic activity (section Metabolic Activity ). 

Endocytosis has been shown to be dependent on metabolic activity. A block of metabolic activity might also be used to differentiate endocytosis from fusion or cellular association. Either glycolysis or oxidative phosphorylation can be affected, or both. 

Incubation at 4°C (see section Energy Dependence on Liposome Uptake and Fusion with Cell Membranes ) and a block of metabolic activity (see section Metabolic Activity ) might also be used to block endocytosis and to detect cellular association or fusion. 

Figure 5.6 General scheme of lipoprotein metabolism. Triacylglycerols and cholesterol are exported from the liver in VLDLs, containing apolipoprotein B-lOO they further acquire apo-C-I, II, III and apo-E from circulating HDL. Apo-C-II activates lipoprotein lipase to remove fatty acids from VLDLs. As triacylglycerols are removed, VLDLs transform to IDEs and finally LDLs. LDLs are the main vehicle for transfer of cholesterol to the tissues uptake of LDL occurs primarily in the liver through LDL-receptor-mediated endocytosis, which requires the presence of apo-B-100. HDLs are synthesised essentially devoid of cholesterol or triacylglycerol and provide a circulating source of apo-C-I, II and apo-E. HDLs gradually accumulate cholesteryl esters, eventually returning these to the liver, mediated by an apo-A-I receptor this is referred to as reverse cholesterol transport. ...

Three processes are involved in transcellular transport across the intestinal epithelial cells simple passive trans-port, passive diffusion together with an efflux pump, and active transport and endocytosis. Simple passive transport is the diffusion of molecules across the membrane by thermodynamic driving forces and does not require direct expenditure of metabolic energy. In contrast, active transport is the movement of molecules across the mem-brane resulting directly from the expenditure of metabolic energy and transport against a concentration gradient. Endocytosis processes include three mechanisms fluid-phase endocytosis (pinocytosis), receptor-mediated endocytosis, and transcytosis (Fig. 6). Endocytosis processes are covered in detail in section Absorption of Polypeptides and Proteins, later. 

Cholesterol, which is largely insoluble in aqueous m a, travels through the blood circulation in the form of Upoprotein complexes. The plasma lipoproteins are a family of globular particles that share common structural features. A core of hydrophobic lipid, principally triacylglycerols (triglycerides) and cholesterol esters, is surrounded by a hydrophilic monolayer of phospholipid and protein (the apolipoproteins) [1-3]. Lipid-apolipoprotein interactions, facihtated byi amphi-pathic protein helices that segregate polar from nonpolar surfaces [2,3], provide the mechanism by which cholesterol can circulate in a soluble form. In addition, the apolipoproteins modulate the activities of certain enzymes involved in Upoprotein metabolism and interact with specific cell surface receptors which take up Upopro-teins by receptor-mediated endocytosis. Differences in the Upid and apoUpoprotein compositions of plasma Upoproteins determine their target sites and classification based on buoyant density. 

After glomerular filtration, small linear peptides undergo intraluminal metabolism, predominantly by exopeptidases in the luminal brush border membrane of the proximal tubules. The resulting amino acids are transcellularly transported back into the systemic circulation [28, 43]. Larger peptides and proteins are actively reabsorbed in the proximal tubules via endocytosis. This cellular uptake is followed by addition of lysosomes... 

Lysosomes and microbodies are single-membrane organelles each of which possess a discrete series of enzymes. Lysosomes (Figure 9.2) contain a wide variety of hydrolases which, at acidic pH, collectively are capable of degrading most classes of biological molecules. To protect the cell from autolysis, enzymic activation involves the metabolic acidification of the lysosomal milieu. Lysosomes feature significantly in endocytosis (Section 9.3). 

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