Lead pathways into humans

Organometallic and organometalloidal compounds can lead to unexpected species that are a serious challenge to cellular systems. For example, Figures 8.2 and 8.3 show the different forms in which uranium can appear in the environment and pathways into humans. 

Several PFCs have been detected in human blood from populations in North and South America, Asia, Australia and Europe [48, 67, 143-146]. Different studies in Europe showed that PFOS is one of the more frequent compound present in human blood [48, 147], and the highest PFOS concentrations were found in Poland, followed by Belgium, being comparable to Sweden, with lowest concentrations in Italy [37]. These results indicate differences in exposure across Europe. However, the sources and pathways of human exposure to PECs are currently not well understood [27]. The wide variety of industrial and consumer applications leads to numerous possibilities for release of PECs into the environment and subsequent exposures to humans via environmental routes and media. However, the relative uniform distribution of blood concentrations of PECs in children and the majority of adult populations points to a common major source, possibly food. 

Insulin also plays a role in fat metabolism. In humans, most fatty acid synthesis takes place in the liver. The mechanism of action of insulin involves directing excess nutrient molecules toward metabolic pathways leading to fat synthesis. These fatty acids are then transported to storage sites, predominantly adipose tissue. Finally, insulin stimulates the uptake of amino acids into cells where they are incorporated into proteins. 

Once returned to the presynaptic terminal, dopamine is repackaged into synaptic vesicles via the vesicular monoamine transporter (VMAT) or metabolized to dihydroxyphenylacetic acid (DOPAC) by monoamine oxidase (MAO). Two alternative pathways are available for dopamine catabolism in the synapse, depending on whether the first step is catalyzed by MAO or catechol-O-methyltransferase (COMT). Thus, dopamine can be either deaminated to 3,4-dihydroxyphenylacetic acid (DOPAC) or methylated to 3-methoxytyramine (3-MT). In turn, deamination of 3-MT and methylation of DOPAC leads to homovanillic acid (HVA). In humans, cerebrospinal fluid levels of HVA have been used as a proxy for levels of dopaminergic activity within the brain (Stanley et al. 1985). 

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