Receptors coenzymes

The primary transporter of cholesterol in the blood is low density Hpoprotein (LDL). Once transported intraceUularly, cholesterol homeostasis is controlled primarily by suppressing cholesterol synthesis through inhibition of P-hydroxy-P-methyl gluterate-coenzyme A (HMG—CoA) reductase, acyl CoA—acyl transferase (ACAT), and down-regulation of LDL receptors. An important dmg in the regulation of cholesterol metaboHsm is lovastatin, also known as mevinolin, MK-803, and Mevacor, which is an HMG—CoA reductase inhibitor (Table 5). 

Pyridoxal phosphate is a coenzyme for many enzymes involved in amino acid metabolism, especially in transamination and decarboxylation. It is also the cofactor of glycogen phosphorylase, where the phosphate group is catalytically important. In addition, vitamin Bg is important in steroid hormone action where it removes the hormone-receptor complex from DNA binding, terminating the action of the hormones. In vitamin Bg deficiency, this results in increased sensitivity to the actions of low concentrations of estrogens, androgens, cortisol, and vitamin D. 

FIGURE 9. Endogenous lipoprotein metabolism. In liver cells, cholesterol and triglycerides are packaged into VLDL particles and exported into blood where VLDL is converted to IDL. Intermediate-density lipoprotein can be either cleared by hepatic LDL receptors or further metabolized to LDL. LDL can be cleared by hepatic LDL receptors or can enter the arterial wall, contributing to atherosclerosis. Acetyl CoA, acetyl coenzyme A Apo, apolipoprotein C, cholesterol CE, cholesterol ester FA, fatty acid HL, hepatic lipase HMG CoA, 3-hydroxy-3-methyglutaryl coenzyme A IDL, intermediate-density lipoprotein LCAT, lecithin-cholesterol acyltransferase LDL, low-density lipoprotein LPL, lipoprotein lipase VLDL, very low-density lipoprotein. 

ACE-I, angiotensin-converting enzyme inhibitors ARB, angiotensin-receptor blockers AZA, azathioprine CMV, cytomegalovirus CPK, creatinine phos-phokinase CSA, cyclosporine HMG-CoA, 3-hydroxy 3-methylglutaryl coenzyme A reductase K+, potassium LFTs, liver function tests Rl, renal insufficiency SCr, serum creatinine SRL, sirolimus TAC, tacrolimus TMP-SMX, trimethoprim-sulfamethoxazole. 

Figure 13.3. An overview of the chemical events at a cholinergic synapse and agents commonly used to alter cholinergic transmission acetyl CoA, acetyl coenzyme A Ch, choline. Nicotine and scopolamine bind to nicotinic and muscarinic receptors, respectively (nicotine is an agonist while scopolamine is an antagonist). Most anti-Alzheimer drugs inhibit the action of the enzyme cholinesterase.

One model of an ionic mechanism of action of Li+ in affective disorders has been proposed, in which the receptors for Li+ are ion channels and cation coenzyme receptor sites, and in which the presence of intracellular Li+ in excitable cells results in the displacement of exogenous Na+ and/or other intracellular cations [13]. It has been suggested that this could lead to a decrease in the release of neurotransmitters alternatively it may be that this intracellular Li+ is altering a preexisting, disease-related electrolyte imbalance [14]. A number of observations of such imbalances in affective disorders have been made depression is associated with elevated levels of intracellular Na+ [15] retention of Li+ is observed in manic-depressive patients prior to an episode of mania [ 16] and Na+/K+ activity is defective during both mania and depression [17]. 

Imperiali B, McDonnell KA, Shogren-Knaak M (1999) Design and Construction of Novel Peptides and Proteins by Tailored Incorparation of Coenzyme Functionality. 202 1-38 Jacques VjDesreux JF(2002) New Classes of MRI Contrast Agents. 221 123-164 James TD, Shinkai S (2002) Artificial Receptors as Chemosensors for Carbohydrates. 218 159-200... 

Mechanism of Action Acts as a coenzyme for various metabolic functions, including fat and carbohydrate metabolism and protein synthesis. Therapeutic Effect Necessary for cell growth and replication, hematopoiesis, and myelin synthesis. Pharmacokinetics In the presence of calcium, absorbed systemically in lower half of ileum. Initially, bound to intrinsicfactor this complex passes down intestine, binding to receptor sites on ileal mucosa. Protein binding High, Metabolized in the liver. Primarily eliminated unchanged in urine. Half-life 6 days. 

Also known as statins. HMG CoA reductase (Hydroxymethyl-Glutaryl Coenzyme A Reductase) inhibitors block the synthesis of cholesterol in liver by competitively inhibiting HMG CoA reductase activity, also cause depletion of critical intracellular pools of sterols and increased transcription of LDL receptors leading to enhanced removal from plasma of LDL cholesterol and LDL precursors. They also reduce hepatic synthesis of VLDL, increase plasma HDL. Reduction of LDL occurs over 4-6 weeks. 

Enzymes, composed of various amino acids, constitute hydrophobic interior and hydrophilic exterior by arranging in space the appropriate amino acid residues. The hydrophobic receptor site is usually located inside and the hydrophilic amino acid residues located on the surface of enzyme are heavily solvated by water molecules in aqueous solution. Then, the supramolecular interactions with specific coenzymes, substrates, and inhibitors inevitably accompany extensive dehydration and conformational change of both enzyme and ligand. 

Complementary structures of biological materials, especially those of proteins, often result in specific recognitions and various types of biological affinity. These include many pairs of substances, such as enzyme-inhibitor, enzyme-substrate (analog), enzyme-coenzyme, hormone-receptor, and antigen-antibody, as summarized in Table 11.2. Thus, bioaffinity represents a useful approach to separating specific biological materials. 

Apolipoproteins The apolipoproteins associated with lipoprotein particles have a number of diverse functions, such as providing recognition sites for cell-surface receptors, and serving as activators or coenzymes for enzymes involved in lipoprotein metabolism. Some of the apolipoproteins are required as essential structural components of the particles and cannot be removed (in fact, the particles cannot be produced without them), whereas others are transfered freely between lipoproteins. Apolipoproteins are divided by structure and function into five major classes, A through E, with most classes having subclasses, for example, apo A-l and apo C-ll. [Note Functions of all of the apolipoproteins are not yet known.]... 

Why do we need vitamins Early clues came in 1935 when nicotinamide was found in NAD+ by H. von Euler and associates and in NADP+ by Warburg and Christian. Two years later, K. Lohman and P. Schuster isolated pure cocarboxylase, a dialyz-able material required for decarboxylation of pyruvate by an enzyme from yeast. It was shown to be thiamin diphosphate (Fig. 15-3). Most of the water-soluble vitamins are converted into coenzymes or are covalently bound into active sites of enzymes. Some lipid-soluble vitamins have similar functions but others, such as vitamin D and some metabolites of vitamin A, act more like hormones, binding to receptors that control gene expression or other aspects of metabolism. 

Folate coenzymes, 803, 804. See also Folic acid Folate receptors 805 3-Fold axis 333 Folding patterns... 

FIGURE 26.3 Tubocurarine competes with acetylcholine (ACh) at cholinergic receptor. CHAT = choline acetylase, CoA = coenzyme A. 

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