Distribution in Mammals

KB Bischoff, RG Brown. Drug distribution in mammals. Chem Eng Prog Symp 62 33-45, 1966. 

GPCR genes were collected from SEVENS database, in which genes are classifred into the 57 known GPCR subfamilies, or into orphan or unknown receptor families. Table 1 shows the example case of family distribution in mammal GPCRs. 

Ganz T, Nemeth E. Regulation of iron acquisition and iron distribution in mammals. Biochim. Biophys. Acta 2006 1763 690-699. 44. 

Bischoff, K.B. Applications of mathematical model for drug distribution in mammals. In Hershey, D., ed. Chemical Engineering in Medicine and Biology. New York Plenum Press, 1967. pp. 417-446. 

The second rate-limiting step in glycolysis is the conversion of PEP to pyruvate, catalysed by pyruvate kinase. There are a number of isoenzymes of pyruvate kinase, and they have been classified according to their properties and their tissue distribution in mammals. The avian enzymes have then been fitted to the mammalian classification where appropriate (Table 3.4). Those enzymes present in tissues that carry out gluconeogenesis generally have more... 

The a subunits, for which two isoforms exist in mammals (al, a2), contain conventional protein serine/threonine kinase domains at the N-terminus, with a threonine residue in the activation loop (Thr-172) that must be phosphorylated by upstream kinases (see below) before the kinase is active. The kinase domain is followed by an autoinhibitory domain, whose effect is somehow relieved by interaction with the other subunits. The C-terminal domain of the a subunit is required for the formation of a complex with the C-terminal domain of the (3 subunit, which in turn mediates binding to the y subunit. The al and a2 catalytic subunit isoforms are widely distributed, although a2 is most abundant in muscle and may be absent in cells of the endothelial/hemopoietic lineage. 

Phospholipase D is widely distributed in bacteria, fungi, plants and animals, and is present in almost all mammalian cells [3]. In mammals, it occurs as alternatively spliced products of two genes (PLD1 andPLD2) (Fig. 3). Most mammalian cells express different levels of both isoforms. Both PLD1 and PLD2 have four conserved sequences (I-IV), and sequences I and IV contain the HXKX4D (HKD) motif that is characteristic of the PLD superfamily, which includes bacterial endonucleases, phospholipid synthases, viral envelope... 

These are of primary signihcance in the biosynthesis of organohalogen compounds (Neilson 2003), which are distributed among mammals, marine biota, bacteria, and fungi. 

Herrada G. and Dulac C. (1997). A novel family of putative pheromone receptors in mammals with a topographically oiganised and sexually dimorphic distribution. Cell 90, 763-773. 

In mammals, as in yeast, several different metallothionein isoforms are known, each with a particular tissue distribution (Vasak and Hasler, 2000). Their synthesis is regulated at the level of transcription not only by copper (as well as the other divalent metal ions cadmium, mercury and zinc) but also by hormones, notably steroid hormones, that affect cellular differentiation. Intracellular copper accumulates in metallothionein in copper overload diseases, such as Wilson s disease, forming two distinct molecular forms one with 12 Cu(I) equivalents bound, in which all 20 thiolate ligands of the protein participate in metal binding the other with eight Cu(I)/ metallothionein a molecules, with between 12-14 cysteines involved in Cu(I) coordination (Pountney et ah, 1994). Although the role of specific metallothionein isoforms in zinc homeostasis and apoptosis is established, its primary function in copper metabolism remains enigmatic (Vasak and Hasler, 2000). 

Durbin, P. W. (1962). Distribution of the transuranic elements in mammals, Health Phys. 8, 665. 

Milbrath, D.S., M. Eto, and J.E. Casida. "Distribution and Metabolic Fate in Mammals of the Potent Convulsant and GABA Antagonist ferf-Butylbicyclophosphate and its Methyl Analog."... 

Chlordane is readily absorbed by warm-blooded animals through skin, diet, and inhalation. It is quickly distributed in the body and tends to concentrate in liver and fat (WHO 1984). Up to 75% of a single oral dose of chlordane administered to rats and mice was absorbed in the gut, and up to 76% of an aerosol dose was absorbed in the respiratory tract (Nomeir and Hajjar 1987). Rabbits absorbed 33% in the gut following oral administration (USEPA 1988). Chlordane residues in mammals were usually not measurable 4 to 8 weeks after cessation of exposure (Ingle 1965). Chlordane persistence in human serum and whole body was estimated at 88 days and 21 days, respectively this compares to a Tb 1/2 of about 23 days in rats fed chlordane for 56 days (USEPA 1980). 

Rhodanese is widely distributed in the body, but activity levels in mammals are highest in the mitochondrial fraction of liver. Rhodanese activity levels in catalyzing the transformation of thiosulfate to thiocyanate are limited by the availability of sulfur. Minor detoxification pathways for cyanide include exhalation in breath as HCN, and as C02 from oxidative metabolism of formic... 

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