Trapping, metabolic

Despite addressing different cellular functions, imaging the potassium space by or by cellular metabolic trapping of FDG, the size and severity of the defects obtained with both radionuclides by PET are virtually identical [66, 67], indicating equivalent preservation of these two measures of viability. 

A recent study aiming at validating the fatty acid analog FTP in the isolated perfused rat heart showed that FTP as a metabolically trapped FAO probe is capable of indicating rates of myocardial oxidation of exogenous long-chain fatty acids [187]. 

N]NPC is a potential metabolic trapping tracer for estimation of cholineesterase activity in vivo295,296, but it is very easily hydrolysed even in a weak alkaline solution (as shown in equation 129). Consequently, its labelling must be carried out under strictly anhydrous conditions. 

Much of the absorbed riboflavin is phosphorylated in the intestinal mucosa by flavokinase and enters the bloodstream as riboflavin phosphate this metabolic trapping is essential for concentrative uptake of riboflavin into en-terocytes (Gastaldi et al., 2000). Parenterally administered free riboflavin is also largely phosphorylated in the intestinal mucosa. It is not clear whether this is the result of enterohepatic recycling of the vitamin or simply uptake of free riboflavin into the intestinal mucosa from the bloodstream. 

The phosphorylated vitamers are dephosphorylated by membrane-bound alkaline phosphatase in the intestinal mucosa pyridoxal, pyridoxamine, and pyridoxine are all absorbed rapidly by carrier-mediated diffusion. Intestinal mucosal cells have pyridoxine kinase and pyridoxine phosphate oxidase (see Figure 9.1), so that there is net accumulation of pyridoxal phosphate by metabolic trapping. Much of the ingested pyridoxine is released into the portal circulation as pyridoxal, after dephosphorylation at the serosal surface. 

Tissue uptake of vitamin Be is again by carrier-mediated diffusion of pyridoxal (and other unphosphorylated vitamers), followed by metabolic trapping by phosphorylation. Circulating pyridoxal and pyridoxamine phosphates are hydrolyzed by extracellular alkaline phosphatase. All tissues have pyridoxine kinase activity, but pyridoxine phosphate oxidase is found mainly in the liver, kidney, and brain. 

The principal substrate for glutamylation is free tetrahydrofolate one-carbon substituted folates are poor substrates. Because the main circulating folate, and the main form that is taken up into tissues, is methyl-tetrahydrofolate, demethylation by the action of methionine synthetase (Section 10.3.3) is essential for effective metabolic trapping of folate. In vitamin B12 deficiency, when methionine synthetase activity is impaired, there wUl be impairment of the retention of folate in tissues. 

Dietary biotin bound to avidin (Section 11.6) is unavailable, but intravenously administered avidin-biotin is biologically active. Cells in culture are not inhibited by the addibon of avidin to the culmre medium, and can take up the avidin-biotin complex by pinocytosis followed by lysosomal hydrolysis, releasing free biotin. Unlike other B vitamins, for which concentrative uptake into tissues is achieved by facilitated diffusion, followed by metabolic trapping, the incorporation of biotin into enzymes is slow and cannot be considered part of the uptake process. 

The first step in pantothenic acid utilization is phosphorylation (see Figure 12.2). Pantothenate kinase is rate-limiting, so that, unlike many vitamins that are accumulated by metabolic trapping, there can be significant accumulation of free pantothenic acid in tissues. Intracellular concentrations may be as high as 200 to 500 ixmo per L. 

Fig. 33.2. F-2-fluoro-2-deoxy-D-glucose (FDG) is actively taken up by glucose transport proteins into the cell. Within the cell, FDG is metabolized to FDG-6-phosphate, which is metabolically trapped...

Concentrative uptake of the material being transported may be achieved in three main ways protein binding, metabolic trapping and active transport. These last two mechanisms are both ATP dependent. 

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