Lipid soluble protein

The number of sugar residues linked to the aglycone-pottion (1 1) or the hydroxylation of the aglycone markedly influences water and lipid solubility, protein... 

Hemoperfusion is like hemodialysis except that blood is circulated extracorporeally through a column with adsorbent material like resin or charcoal, which binds molecules electrostatically. The molecules likely to be removed are characterized as poorly dialyzable, lipid-soluble, protein bound. Among the indications for hemoperfusion in the management of poisoning include the presence of a poison in a patient with impairment of excretory system (i.e. damaged kidneys), intoxication of a drug known to produce delayed toxicity or metabolized to a more toxic metabolite (i.e. paraquat or methotrexate), deterioration of the clinical state of the poisoned patient despite conservative therapy (i.e. convulsions or cardiac arrhythmias following theophylline intoxication), or development of coma as a complication. 

Highly hpid-soluble, extensively protein-bound, highly potent local anesthetics, such as tetracaine, bupivacaine, and etidocaine, are much more cardiotoxic than less lipid-soluble, protein-bound, and potent local anesthetics, such as lidocaine and prilocaine. 

Agent Potency Onset Duration PK Lipid solubility Protein binding, %... 

Recently, incorporation of labeled amino acids into a lipid-soluble protein component was also reported in animal systems (Kadenbach and Hadvary, 1973 Burke and Beattie, 1973). These findings naturally raise the question of whether the mitochondrial genome might also code for some lipoproteins used for membrane synthesis outside of mitochondria. A number of other enzyme reactions also correlate with mitochondrial protein synthesis, but the evidence is not as convincing as in the case of cytochrome oxidase and ATPase. We will discuss these possibilities briefly. 

Pharmacokinetic constants for the absorption and elimination of pralid-oxime have been determined in man83. a pharmacokinetic model for flow, lipid solubility, protein binding and saturation-IImited metabolism of thiopental has permitted the a priori prediction of bodily distribution conslsten with experiment . Imipramine and its metabolites are rapidly distributed in the rat and renally and biliary excreted with enterohepatic circulation . Mathematical models have been established for the pharmacokinetics of neurohypophysial and related peptides . The oral administration of 2,3,5, triiodebenzoic acid in goats and a cow by whole-body radioactivity retention showed a rapid distributive and subsequent exponential elimination phase with the metabolites formed by deiodination . Bishydroxycoumarin shows dose-dependent first order elimination in man but not in other species and has been assigned to dose effects on el imi nation . ... 

Water solubility (polarity) is essential for excretion. Even though lipid-soluble compounds may also be excreted to primary urine, they are usually at least partially reabsorbed. The metabolites formed in the liver and extrahe-patic tissues remain free (i.e., not bound to proteins) and are, therefore, readily excreted. 

Bilayer phase transitions are sensitive to the presence of solutes that interact with lipids, including multivalent cations, lipid-soluble agents, peptides, and proteins. 

Certain proteins are found to be covalently linked to lipid molecules. For many of these proteins, covalent attachment of lipid is required for association with a membrane. The lipid moieties can insert into the membrane bilayer, effectively anchoring their linked proteins to the membrane. Some proteins with covalently linked lipid normally behave as soluble proteins others are integral... 

The second question concerns molecules that are not lipid-soluble How are the transmembrane concentration gradients for non-hpid-soluble molecules maintained The answer is that membranes contain proteins. 

Most of the lipid-soluble hormones are bound to rather specific plasma transport proteins. 

Like other cells, a neuron has a nucleus with genetic DNA, although nerve cells cannot divide (replicate) after maturity, and a prominent nucleolus for ribosome synthesis. There are also mitochondria for energy supply as well as a smooth and a rough endoplasmic reticulum for lipid and protein synthesis, and a Golgi apparatus. These are all in a fluid cytosol (cytoplasm), containing enzymes for cell metabolism and NT synthesis and which is surrounded by a phospholipid plasma membrane, impermeable to ions and water-soluble substances. In order to cross the membrane, substances either have to be very lipid soluble or transported by special carrier proteins. It is also the site for NT receptors and the various ion channels important in the control of neuronal excitability. 

Figure 5,4 Pharmacokinetics. The absorption distribution and fate of drugs in the body. Routes of administration are shown on the left, excretion in the urine and faeces on the right. Drugs taken orally are absorbed from the stomach and intestine and must first pass through the portal circulation and liver where they may be metabolised. In the plasma much drug is bound to protein and only that which is free can pass through the capillaries and into tissue and organs. To cross the blood brain barrier, however, drugs have to be in an unionised lipid-soluble (lipophilic) form. This is also essential for the absorption of drugs from the intestine and their reabsorption in the kidney tubule. See text for further details...

With few exceptions, small particles of vegetable foods are generally stripped of their more accessible nutrients during digestion in the GI tract. In this way starch, protein, fat and water-soluble small components (sugars, minerals) are usually well absorbed. This is not always the case, however, for larger food particles or for molecules that cannot diffuse out of the celF tissue. Neither is it the case for the lipid-soluble components. These need to be dissolved in lipid before they can be physically removed from the cell to the absorptive surface, since the cell wall is unlikely to be permeable to lipid emulsions or micelles, and the presence of lipases will strip away the solvating lipid. 

The availability of the purified transporter in large quantity has enabled investigation of its secondary structure by biophysical techniques. Comparison of the circular dichroism (CD) spectrum of the transporter in lipid vesicles with the CD spectra of water-soluble proteins of known structure indicated the presence of approximately 82% a-helix, 10% ) -turns and 8% other random coil structure [97]. No / -sheet structure was detected either in this study or in a study of the protein by the same group using polarized Fourier transform infrared (FTIR) spectroscopy [98]. In our laboratory FTIR spectroscopy of the transporter has similarly revealed that... 

In the case of PS II membrane proteins, as discussed above, the hydrophobic and hydrophilic pairs of attached lipids can partially support the protein complex at the air-water interface, despite their large size and density. However, in the case of PS II core complex, the detergent strips the attached lipids and some extrinsic proteins. The remaining protein complex is water soluble. It is very difficult to prepare a stable monolayer of water-soluble proteins with the Langmuir method. Indeed, it is hard to directly prepare a stable monolayer of PS II core complex because of its water solubility as well as density. One possible solution is to change the density and ionic strength of the subphase [9]. 

As patients lose exocrine function of the pancreas, they have decreased ability to absorb lipids and protein ingested with normal dietary intake. Weight loss from nutritional malabsorption is a common symptom of chronic pancreatitis not often seen in acute pancreatitis. Fatty- or protein-containing stools are also common carbohydrate absorption is usually unaffected. Even though patients with chronic pancreatitis have decreased ability to absorb lipid from the gastrointestinal tract, there does not appear to be an increased incidence of fat-soluble vitamin deficiency in these patients.34... 

The lipid bilayer arrangement of the plasma membrane renders it selectively permeable. Uncharged or nonpolar molecules, such as oxygen, carbon dioxide, and fatty acids, are lipid soluble and may permeate through the membrane quite readily. Charged or polar molecules, such as glucose, proteins, and ions, are water soluble and impermeable, unable to cross the membrane unassisted. These substances require protein channels or carrier molecules to enter or leave the cell. 

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