Disease relevance of TMTC1

• Olfactory neuroblastoma (OLF NB) is an uncommon neurogenic tumor arising in the nasal cavity [1].
• They are effective antihypertensive agents in animal models of hypertension sustained by OLF (reduced renal mass-Na+ and DOCA-salt hypertension in rats) [2].
• Two additional OLFs with Mr around 400 eluted in a late subfraction FIV/8 which resolved after reverse-phase HPLC into a more polar OLF- (water phase) and a more apolar OLF-2 (20% acetonitrile) [3].

High impact information on TMTC1

• In contrast, a mutant fragment in which the single basic residue (Arg99) in the minor loop ("Omega-loop") of the second type I module was converted to a glycine had an essentially normal melting profile but exhibited no binding to heparin and failed to promote matrix-driven translocation [4].
• It is believed these compounds, collectively known as either digitalis-like (DLF) or ouabain-like (OLF) factors, may be endogenous hormones regulating the biological activity of the sodium pump and its isoforms [5].
• The Arg99 beta mutant associated with the alpha subunit, but the resulting heterodimer failed to enhance intracellular cyclic AMP production in a gonadotrophin-responsive transformed murine Leydig cell line [6].
• This unique immunoreactive species is liekly to have structural similarity to both digoxin and ouabain and thus may represent a metabolic link between DLIF and OLF [7].
• The average extraction efficiency is 400 pmol digoxin equivalent (range 300-500) and 42 pmol ouabain equivalent (range 37-50) per gram of adrenal cortex for DLIF and OLF, respectively [7].

Chemical compound and disease context of TMTC1

• The highest plasma concentrations of endogenous ouabain and OLF were found in congestive heart failure, aldosterone producing adenoma, human and animal models of volume expanded hypertension (reduced renal mass and DOCA-salt hypertension), and in Milan hypertensive rats (MHS) [2].

Anatomical context of TMTC1

• It has been suggested that endogenous substances (known as ouabain-like factors, OLF), secreted from the central nervous system in response to salt and water retention, inhibit the cell membrane Na+/K+ pump in the renal tubules and reduce sodium reabsorption [2].
• Paravertebral ligamentous ossification is designated as the disorder caused by frequently coexisting ossification of paravertebral ligaments, DISH, OPLL, and OLF [8].
• This area of investigation has been rejuvenated as of late with near structural determination of two ouabain-like isolates from human plasma (OLF) and bovine hypothalamus (HIF) which are apparently the same compound and the isolation and structural elucidation of a natriuretic metabolite of gamma-tocopherol [9].
• False negative in spinal cord monitoring using spinal cord-evoked potentials following spinal cord stimulation during surgery for thoracic OPLL and OLF [10].
• Sagittal splitting laminoplasty for spinal canal enlargement for ossification of the spinal ligaments (OPLL and OLF) [11].

Associations of TMTC1 with chemical compounds

• DLIF (digoxin-like immunoreactive factor) and OLF (ouabain-like factor) are endogenous steroid-like ligands (approximately 781 and 595 Da, respectively) with molecular and structural properties similar to the plant-derived cardiac glycosides, digoxin and ouabain [7].

Analytical, diagnostic and therapeutic context of TMTC1

• In this study, site-directed mutagenesis of MADH, kinetic data, and thermodynamic analysis are used to probe the molecular basis for stabilization of the protein complex by an interprotein salt bridge between Arg99 of amicyanin and Asp180 of the alpha subunit of MADH [12].

References