BIOC520: Biological Chemistry

L-3: Amino Acids

                                                            L-3
                                                            8/5/97
                                                            Noiva
AMINO ACIDS
OBJECTIVES:
 	1.   Know the roles of amino acids in the body.
 	2.   Know the structures of the amino acids.
	3.   Know the chemical properties of the amino acids.

READING:
     Marks, Marks, and Smith: Chapter 7, pp. 67-77
     Devlin:   Chapter 2, pp. 24-39.

CLINICAL CORRELATIONS:
     Michael Sichel - sickle cell disease
     Marks, Marks, and Smith:  pp. 67, 72-74, 76
     Cal Kulis - renal calculi
     Marks, Marks, and Smith:  pp. 67, 72-73, 76

LECTURE:
I.   Function of amino acids
     A.   Building blocks of polypeptides (Devlin Fig. 2.1, pg 25, Fig.
          2.8, pg 28)
          1.   polymerized to form polypeptides
               a.   linked by a peptide bond
               b.   synthesized during translation of messenger RNA
          2.   primary structure of a protein is the sequence of amino
               acids
          3.   both peptides and polypeptides can be functional
     
	(Fig. 2.8 Devlin: amino acids forming di-, tri-peptides)

	Structure -00C-CH2-CH2-NH3+	GABA

	Structure +H3N-CH2-CH2-SO3-	TAURINE

     B.   Amino acids may be functional 
          1.   neurotransmitters
               -    glutamate and aspartate (excitory)
               -    glycine, taurine, and  -aminobutyric acid (GABA)
                    (inhibitory)

     C.   Precursors to other molecules 
          1.   metabolic intermediates
               -  citrulline and ornithine in urea cycle
               -  can be metabolized to form glucose or acetyl CoA
          2.   neurotransmitters
               -  serotonin, dopamine, epinephrine, etc.
          3.   thyroxine (thyroid hormone)   
          4.   porphyrins
          5.   creatine (energy storage)
          6.   histamine (mediator of immune response)
          7.   nucleotide synthesis
               -  S-adenosylmethionine
II.  Structure of amino acids (Devlin, Fig. 2.2, pg 25)
     A.   20 standard alpha-amino acids (Devlin, Fig. 2.3, pg 26)
          1.   Structure. Learn the structures.
               -    alpha-carbon
               -    alpha-amino group
               -    alpha-carboxyl group
               -    side chain (R group)
          
          
          2.   "standard" amino acids are encoded by messenger
               RNA
          3.   Amino acids are abbreviated by a 3-letter and
               1-letter code (Devlin, Tab. 2.1,
                                   pg 27).  Learn the three letter code.
     B.   Some amino acids are not incorporated into proteins
          during translation
          1.   Modified amino acids
               a.   Hydroxyproline and hydroxylysine (Devlin, Fig. 2.37,
                    pg 50)
                    i.   hydroxylated enzymatically after translation
                    ii.  important in collagen structure

		(Structures of phosphoserine, 4-OH-proline, 5-OH-lysine)

               	b.   phosphoamino acids
                     i.   Tyr, Ser, Thr hydroxyl groups can be 
                          phosphorylated
                     ii.  important in activation and inhibition of
                          enzymatic or signalling activity
	   2.   Other important amino acids (Fig. 4-22)
              	a.   Urea cycle intermediates
               		-    ornithine, citrulline, arginosuccinate
              	b.   Thyroid hormone (thyroxine)
              	c.    -aminobutyric acid (GABA)
              	      - neurotransmitter

 	(Structures of histamine, dopamine, thyroxine here)

	(Figure 2.3 Devlin; structures of 20 amino acids here)

           Abbreviations for the 20 "standard" amino acids
alanine		Ala	A	leucine		Leu	L
arganine	Arg	R	lysine		Lys	K
asparagine	Asn	N	methioneine	Met	M
aspartic acid	Asp	D	phenylalanine	Phe	F
cysteine	Cys	C	proline		Pro	P
glycine		Gly	G	serine		Ser	S
glutamine	Gln	Q	threonine	Thr	T
glutamic acid	Glu	E	tryptophan	Trp	W
histidine	His	H	tyrosine	Tyr	Y
isoleucine	Ile	I	valine		Val	V

III. Chemical Properties of Amino Acids
     A.   Physical characteristics
          1.   Charge
               a.   Amino acids are dipolar ions (zwitterions) at neutral
                    pH
                    i.   zwitterion is a dipolar molecule with pos. and
                         neg. charges spatially separated
                    ii.  definition of zwitterion in book is incorrect
               b.   Ionic states of amino acids depend on pH
                    i.   amino acids have two or three dissociable protons
                         (Marks Table 7.2 pg. 73) Learn this table
     
			(Table 7.2 Marks here)

                    ii.  pKa of the dissociable proton and the pH
			determine its degree of dissociation
			 (Marks Fig 7.15 pg. 73)

			(Marks table here)

	H-H equation: pH = pKa + log{[A-]/[HA]}

    
	(Fig. 2.15 Devlin: titration of amino acid leu here)
	(Fig. 2.14 Devlin: ionic forms of leucine vs pH)



     2.   Titration curve of an amino acid (Devlin Fig. 2.14-2.17 pp.
         33-34)
         a.   calculated using the H-H equation
         b.   Isoelectric point (pI) - pH at which the molecule has a net
              charge = 0 (average of the two appropriate pKa values)

		(Fig. 2.17 Devlin: titration of glutamic acid here)

     3.   Polarity (Devlin Fig. 2.22, pg. 38)
         a.   nine nonpolar amino acids
              i.   tend to orient to the inside of proteins
              ii.  Gly, Ala, Val, Leu, Ile, Met, Pro, Phe, Trp
         b.   eleven polar amino acids
              i.   tend to orient to the outside of proteins
              ii.  Ser, Thr, Tyr, Asp, Glu, Asn, Gln, Cys, Arg, Lys, His            
     4.   Hydropathicity - index of solubility characteristics in H2O
         a.   combines hydrophobic and hydrophilic tendencies
         b.   can be used to predict protein structure

    Hydrophobic    Ile>Val>Leu>Phe>Met      (listed from most hydrophobic)

    Less Hydrophobic    Ala>Gly>Cys>Trp>Tyr>Pro>Thr>Ser

    Hydrophilic    His>Glu>Asn>Gln>Asp>Lys>Arg  (arg is most hydrophilic)

    5.   UV absorbance
         a.   aromatic a.a.s (Trp, Tyr, Phe) absorb UV light
         b.   absorbs UV light between 260-280 nm

B.  Stereochemistry
    1.   Most amino acids have optical activity
         a.   chiral centers are asymmetric centers (usually carbons)
         b.   à-carbon of amino acids is chiral  
         c.   chirality yields stereospecificity
         d.   Gly is not chiral (has no à-carbon)

	(Structures of L-glyceraldehyde, L-amino acid here)

    2.   L and D enantiomers (stereoisomers)
         a.   enantiomers are nonsuperimposable mirror images of the same
              molecule
              i.   L is levorotatory, D is dextrarotatory
         b.   L and D nomenclature from L and D-glyceraldehyde (Fisher
              convention)
              i.   not equivalent to R and S
              ii.  most natural a.a.s are L
              iii. some a.a.s are R, some are S
         c.   L and D forms are chemically and physically distinguishable
              i.   different activity, melting points, and spectra

C.  Cysteine can form disulfide bonds (Devlin Fig. 2.12, pg. 30)
    1.   cysteine is the reduced form (sulfhydryl)
    2.   cystine is the oxidized form (disulfide)
    3.   disulfide bridges formed between cysteines are
         important in protein structure
          

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