Amino physiological

Tyrosine and cystine have been included primarily for students of biochemistry, physiology and medicine these two amino-acids might, however, be omitted by other students. 

All the amino-acids of physiological importance are a-amino-acids, e.g. (in addition to the above compounds), alanine or a-amino-propionk acid, CHaCH(NH,)COOH, and leucine or a-amino-Y-dimethyl-rt-butyric acid, (CH,)aCHCH,CH(NHa)COOH, and naturally occurring samples (except glycine) are therefore optically active. 

P-Endorphin. A peptide corresponding to the 31 C-terminal amino acids of P-LPH was first discovered in camel pituitary tissue (10). This substance is P-endorphin, which exerts a potent analgesic effect by binding to cell surface receptors in the central nervous system. The sequence of P-endorphin is well conserved across species for the first 25 N-terminal amino acids. Opiates derived from plant sources, eg, heroin, morphine, opium, etc, exert their actions by interacting with the P-endorphin receptor. On a molar basis, this peptide has approximately five times the potency of morphine. Both P-endorphin and ACTH ate cosecreted from the pituitary gland. Whereas the physiologic importance of P-endorphin release into the systemic circulation is not certain, this molecule clearly has been shown to be an important neurotransmitter within the central nervous system. Endorphin has been invaluable as a research tool, but has not been clinically useful due to the avadabihty of plant-derived opiates. 

Naturally Occurring Compounds. Many derivatives of iadole are found ia plants and animals where they are derived from the amino acid tryptophan. Several of these have important biological function or activity. Serotonin [50-67-9] (12) functions as a neurotransmitter and vasoconstrictor (35). Melatonin [73-31-4] (13) production is controlled daily by the circadian cycle and its physiological level iafluences, and seasonal rhythms ia humans and other species (36). Indole-3-acetic acid [87-51-4] (14) is a plant growth stimulant used ia several horticultural appHcations (37). 

CCK is found in the digestive tract and the central and peripheral nervous systems. In the brain, CCK coexists with DA. In the peripheral nervous system, the two principal physiological actions of CCK are stimulation of gaU. bladder contraction and pancreatic enzyme secretion. CCK also stimulates glucose and amino acid transport, protein and DNA synthesis, and pancreatic hormone secretion. In the CNS, CCK induces hypothermia, analgesia, hyperglycemia, stimulation of pituitary hormone release, and a decrease in exploratory behavior. The CCK family of neuropeptides has been impHcated in anxiety and panic disorders, psychoses, satiety, and gastric acid and pancreatic enzyme secretions. 

Proteins. The most abundant and physiologically diverse natural biopolymers are proteins, which make up enzymes, hormones, and stmctural material such as hair, skin, and connective tissue. The monomer units of natural proteins, a-amino acids, condense to form dipeptides, tripeptides, polypeptides, and proteins. 

Physiological Role of Citric Acid. Citric acid occurs ia the terminal oxidative metabolic system of virtually all organisms. This oxidative metabohc system (Fig. 2), variously called the Krebs cycle (for its discoverer, H. A. Krebs), the tricarboxyUc acid cycle, or the citric acid cycle, is a metaboHc cycle involving the conversion of carbohydrates, fats, or proteins to carbon dioxide and water. This cycle releases energy necessary for an organism s growth, movement, luminescence, chemosynthesis, and reproduction. The cycle also provides the carbon-containing materials from which cells synthesize amino acids and fats. Many yeasts, molds, and bacteria conduct the citric acid cycle, and can be selected for thek abiUty to maximize citric acid production in the process. This is the basis for the efficient commercial fermentation processes used today to produce citric acid. 

The original commercial source of E was extraction from bovine adrenal glands (5). This was replaced by a synthetic route for E and NE (Eig. 1) similar to the original pubHshed route of synthesis (6). Eriedel-Crafts acylation of catechol [120-80-9] with chloroacetyl chloride yields chloroacetocatechol [99-40-1]. Displacement of the chlorine by methylamine yields the methylamine derivative, adrenalone [99-45-6] which on catalytic reduction yields (+)-epinephrine [329-65-7]. Substitution of ammonia for methylamine in the sequence yields the amino derivative noradrenalone [499-61-6] which on reduction yields (+)-norepinephrine [138-65-8]. The racemic compounds were resolved with (+)-tartaric acid to give the physiologically active (—)-enantiomers. The commercial synthesis of E and related compounds has been reviewed (27). The synthetic route for L-3,4-dihydroxyphenylalanine [59-92-7] (l-DOPA) has been described (28). 

It should be noted that in almost all cases only one fold exists for any given sequence. The uniqueness of the native state arises from the fact that the interactions that stabilize the native strucmre significantly destabilize alternate folds of the same amino acid sequence. That is, evolution has selected sequences with a deep energy minimum for the native state, thus eliminating misfolded or partly unfolded structures at physiological temperatures. 

In one of the early experiments designed to elucidate the genetic code, Marshall Nirenberg of the U.S. National Institutes of Health (Nobel Prize in physiology or medicine, 1968) prepared a synthetic mRNA in which all the bases were uracil. He added this poly(U) to a cell-free system containing all the necessary materials for protein biosynthesis. A polymer of a single amino acid was obtained. What amino acid was polymerized ... 

Typical values for pAlg are in the range of 9.0 to 9.8. At physiological pH, the a-carboxyl group of a simple amino acid (with no ionizable side chains) is completely dissociated, whereas the a-amino group has not really begun its dissociation. The titration curve for such an amino acid is shown in Figure 4.7. 

The biologically active form of vitamin Bg is pyridoxal-5-phosphate (PEP), a coenzyme that exists under physiological conditions in two tautomeric forms (Figure 18.25). PLP participates in the catalysis of a wide variety of reactions involving amino acids, including transaminations, a- and /3-decarboxylations, /3- and ") eliminations, racemizations, and aldol reactions (Figure 18.26). Note that these reactions include cleavage of any of the bonds to the amino acid alpha carbon, as well as several bonds in the side chain. The remarkably versatile chemistry of PLP is due to its ability to... 

Pyruvate kinase possesses allosteric sites for numerous effectors. It is activated by AMP and fructose-1,6-bisphosphate and inhibited by ATP, acetyl-CoA, and alanine. (Note that alanine is the a-amino acid counterpart of the a-keto acid, pyruvate.) Furthermore, liver pyruvate kinase is regulated by covalent modification. Flormones such as glucagon activate a cAMP-dependent protein kinase, which transfers a phosphoryl group from ATP to the enzyme. The phos-phorylated form of pyruvate kinase is more strongly inhibited by ATP and alanine and has a higher for PEP, so that, in the presence of physiological levels of PEP, the enzyme is inactive. Then PEP is used as a substrate for glucose synthesis in the pathway (to be described in Chapter 23), instead... 

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