Transthyretin metabolism

Neuropathies can result from mutations that alter the structure or level of expression of PNS myelin proteins (e.g. overexpression of PMP22 in Charcot-Marie-Tooth syndrome (CMT) type 1A), the metabolism of myelin lipids (e.g. metachromatic leukodystrophy), or the capacity of PNS neurons to support their axons in patients with CMT caused by mutations of KIF1B [4] or NF-L [5, 6]. Both acquired and inherited amyloid neuropathies can result from the deposition of poorly soluble proteins, for example cryoglobulins or mutant transthyretins, in and around endoneurial bloodvessels [7-9]. 

The retinyl esters are incorporated into chylomicrons, which in turn enter the lymph. Once in the general circula-tion. chylomicrons arc converted into chylomicron remnants, which arc cleared primarily by the liver. As the c.stcrs enter the hepalocytes. they are hydrolyzed. In the endoplasmic reticulum, the retinol is bound to retinol-binding protein (RBP). This cotnplex is released into the blood or transferred to liver stellate cells fur storage. Within the stellate cells, the retinol is bound to CRBP(I) and e.stcnTicd for storage by ARAT and LRAT. Stellate cells contain up to 95% of the liver vitamin A. stores. The RBP-retinol complex released into the general circulation from hepalocytes or stellate cells, in turn, is bound to transthyretin (TTR), which protects retinol from metabolism and renal excretion. ... 

Ingenbleek Y, Young VR. Significance of transthyretin in protein metabolism. Clin Chem Lab Med 2002 40 1281-91. 

A possible explanation for the highly selective retention of the OH-PCBs in blood may be their structural resemblance with thyroxin. Both rats and mice metabolize PCB 77 by CYPIA to the 1,2-shift metabolite, 4-OH-3,5,3, 4 -PCB, 5-OH 3,3, 4,4 -PCB, and 6-OH-3,3, 4,4 -PCB (McKinley et al. 1993 Morse et al. 1995). Only the 4-OH metabolite was selectively retained, with blood containing 4-OH-3,5,3, 4 -PCB at a concentration 15 times higher than the parent compound, 5 days after oral exposure to PCB 77 in mice (Bergman et al. 1994). This metabolite was found to be bound to a thyroxin-transporting protein (transthyretin) in the blood (Brouwer et al. 1986). Competitive binding studies of OH-PCBs relative to T4 and computer modeling showed that OH-PCBs with the substituents in meta or para positions were much more effective competitors for T4 than if the substituents were bound in an ortho position (Rickenbacher et al. 1986). 

Cerebrospinal Fluid. The proteome of cerebrospinal fluid can provide clues to several neurological disorders, including Alzheimer disease, Parkinson disease, and multiple sclerosis. This study has identified five proteins involved in amyloid-beta metabolism and other metabolisms. These include apolipoprotein Al, cathepsin D, and hemopexin, which were downregulated in Alzheimer patients the transthyretin and pigment epidermal factors were elevated. 

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