Amino Delta

L-alpha-amino-delta-hydroxyvaleric acid has been isolated from Jack Bean seeds (J. Biol. Chem. 239, 1122, 1964). 

While IPNS structurally (Figure 16) and evolutionarily falls within the same enzyme category as the 2-OG-dependent systems, it is unique in that it does not utilize the 2-OG cosubstrate seen in the previously discussed proteins. Rather, it catalyzes the four-electron oxidation of the tripeptide delta-(L-alpha-amino-delta-adipoyl)-L-cysteinyl-D-valine (ACV) to penicillin N via the complete reduction of O2 to water. Although no spectroscopic intermediates in the reaction pathway of IPNS have been characterized in detail, kinetic studies have led to the mechanism proposed in Figure This pathway is based primarily on the results of structural characterizations and... 

Dinitronaphthalene (Delta-dinitronaphtha-lenet 1,6-DNN). Crysts from acet ac, mp 166-67°, bp at 10mm 235°, 360° with decompn (Refs 2 31) CA Registry No 60746-5. It is prepd by the nitration of 2-nitronaphtha- ene with nitric ac/sulfuric ac in hot acet ac (Ref 21) by diazotization of 5-nitro-2-naphthyl-amine followed by treatment of the diazonium salt with Na cobaltinitrite, yield 40% (Ref 36) or by removal of the amino group from 1,6-dinitro-2-naphthylamine by diazotization followed by redn (Ref 17). The temp of expin is 492°(Refl7)... 

If opiates are such addictive and potentially lethal compounds, why does the body respond to them As with the cannabinoids (Chapter 7), it has been discovered that the body and brain possess numerous opiate-specific receptor sites. As many as nine receptor subtypes have been identified, with three of them being the most important p (mu), k (kappa) and 8 (delta). The finding that the distribution of opiate receptors did not parallel the distribution of any known neurotransmitter prompted the search for and identification of a number of endogenous compounds specific to these receptors. These enkephalins and endorphins are manufactured within the brain and other body systems (especially the gut and intestines) and form the body s natural response to pain. They appear to be produced in bulk chains of amino acids called polypeptides , with each active neurotransmitter being composed of around five amino acid molecules. These active neurotransmitters are subsequently cleaved from the larger polypeptides at times of demand for example, it has been demonstrated that the plasma levels of these active compounds rise during childbirth, traumatic incidents and vigorous physical exercise. 

Jim, S., Jones, V., Copley, M. S., Ambrose, S. H. and Evershed, R. P. (2003a) Effects of hydrolysis on the delta C 13 values of individual amino acids derived from polypeptides and proteins. Rapid Communications in Mass Spectrometry 17, 2283 2289. 

Corr, L.T., Sealy, J.C., Horton, M.C. and Evershed, R.P. (2005). A novel marine dietary indicator utilising compound-specific bone collagen amino acid delta C-13 values of ancient humans. Journal of Archaeological Science 32 321-330. 

It is of historical interest to note that the disclosure of U-50488 occurred at roughly the same time as two chemically unrelated compounds which behave as poorly selective kappa agonist analgesics. These are the benzodiazepine, tifluadom (6) [17] and the amino-terminal nonapeptide fragment of dynorphin, Dyn (1-9), (7) (kappa A) = 0.21 nM, mu K = 3.6 nM delta K, = 3.2 nM) [18], which is thought to be the endogenous kappa opioid agonist. 

TTie TOCSY 2D NMR experiment correlates all protons of a spin system, not just those directly connected via three chemical bonds. For the protein example, the alpha proton, Ft , and all the other protons are able to transfer magnetization to the beta, gamma, delta, and epsilon protons if they are connected by a continuous chain—that is, the continuous chain of protons in the side chains of the individual amino acids making up the protein. The COSY and TOCSY experiments are used to build so-called spin systems—that is, a list of resonances of the chemical shift of the peptide main chain proton, the alpha proton(s), and all other protons from each aa side chain. Which chemical shifts correspond to which nuclei in the spin system is determined by the conventional correlation spectroscopy connectivities and the fact that different types of protons have characteristic chemical shifts. To connect the different spin systems in a sequential order, the nuclear Overhauser effect spectroscopy... 

Mauzerall D, Granick S (1995) The occurrence and determination of delta-amino-levulinic acid and porphobilinogen in urine. J Biol Chem 219 435-446... 

A 61-year-old man with epilepsy had altered consciousness after his dose of valproate was increased because of poor seizure control. Electroencephalography showed triphasic waves and high-amplitude delta-wave activity with frontal predominance. Although serum aspartate transaminase and alanine transaminase were normal, the serum ammonium concentration was high at 960 ng/ml (reference range 30-470). Serum amino acid analysis showed multiple minor abnormalities. Valproate was withdrawn. He improved within 4 days... 

Studies in animals suggest that chlorobenzene may also cause injury to the liver. In rats, alkaline phosphatase, SGOT, and delta-amino levulinic acid levels were increased as were liver protoporphyrin and uroporphyrin. Data suggest that the kidneys may be affected following exposure to chlorobenzene as polyuria was noted in rats at high dose levels. Since other chemicals may produce similar effects, these are not specific indicators of chlorobenzene exposure. 

Schoenenberger GA, Maier PF, Tobler HJ, Wilson K, Monnier M. The delta (EEG) sleep inducing peptide (DSIP). XI. Amino acid analysis, sequence, synthesis and activity of the nonapeptide. Pflugers Arch 1978 376 119-129. 

JA Chan, F-C Huang, CJ Sih. The absolute configuration of the amino acids in delta-(alpha-aminoadipyl)cysteinylvaline from Penicillium chrysogenum. Biochemistry 15 177-180, 1976. 

CY Shiau, MF Byford, RT Aplin, JE Baldwin, CJ Schofield. L-Delta-(alpha-amino-adipoyl)-L-cysteinyl-D-valine synthetase thioesterification of valine is not obligatory for peptide bond formation. Biochemistry 36 8798-8806, 1997. 

Mocarelli et al. (1986) conducted a 6-year study on clinical laboratory parameters of children exposed to 2,3,7,8-TCDD following the Seveso accident. ALT, aspartate aminotransferase (AST), GGT, alkaline phosphatase, cholesterol, and triglycerides in plasma and delta amino levulinic acid in urine were monitored yearly in exposed and control groups beginning in June, 1977, approximately 1 year after the incident. The children were 6-10 years old at the time of the accident 69, 528, and 874 resided in the A, B, and R zones, respectively. Chloracne was seen in 19, 0.7, and 4.6%, of the children in areas A, B, and R, respectively. Blood samples were drawn from 69, 83, and 221 children in areas A, B, and R,... 

Today, we know that there are three types of opioid receptors—mu, delta, and kappa receptors [see review 3]. Proenkephalin contains six copies of Met-enkephalins and one copy of Leu-enkephalin. Enkephalins, especially Leu-enkephalin, are believed to be selective to delta receptors. Opiomelano-cortin contains (3-endorphin that has the Met-enkephalin at its amino terminus. (3-Endorphin is a nonselective ligand for mu and delta receptors. 

The predicted amino acid sequence of the clone obtained from NG108-15 cells (Fig. 1) identified the delta opioid receptor as a member of the seven-transmembrane family of G protein-coupled receptors. The receptor had seven hydrophobic, predicted transmembrane domains (TMDs) and close homology to many other G protein-coupled receptors, including receptors for somatostatin, interleukin-8 and angiotensin. This structural homology confirmed the widely held notion that opioid receptors would indeed be members of this enormous family of receptors (the human genome has recently been calculated to contain approximately 950 G protein-coupled receptors [29]). 

Figure 1 Predicted sequence and membrane topography of the murine delta opioid receptor. The mouse sequence was obtained from Genbank (accession No. L07271). Negatively charged amino acids within TMD 2 and 3 are circled and extracellular N-linked glycosylation sites are indicated ( ). Arrows indicate intron/exon boundaries in the mouse genome. (From Ref. 40.)...

Figure 3 Alignment and amino acid sequence homology of delta opioid receptor sequences from different vertebrates. Alignment was performed and presented as described in Figure 2. Sequences were obtained from Genbank. Accession Nos. human, NM-000911 rat, U00475 mouse, LI 1064 and zebrafish (Z.fish), NM-131258 and partial sequences (> <) for monkey, PC2218 and pig, U71149. The sequences for cow, bass, shark, and frog were from reference [32], For explanation of symbols, see Figure 2.

---