2. Amino acids classification based on:
?Standard and Non-standard amino acids (aa)
?Essential and non-essential aa
?Ketogenic and Glucogenic aa
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?Side chain functional group3. Function of essential amino acids
Introduction
?Amino acids as a building blocks of peptides and proteins
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?Proteins are made up of hundreds of smaller units called amino acids that are
attached to one another by peptide bonds, forming a long chain.
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?Protein as a string of beads where each bead is an amino acid.www.khanacademy.org
Genetic Code Specifies 20 L--Amino Acids
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?Proteins are synthesized from the set of 20 L--amino acids encoded by nucleotide
triplets called codons.
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?Common amino acids are those for which at least one specific codon exists inthe DNA genetic code.
?Sequences of peptides and proteins represent by using one- and three letter
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abbreviations for each amino acid.
Genetic information is transcribed from a DNA sequence into mRNA
and then translated to amino acid sequence of a protein
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Fig. 2.1. Textbook of Biochemistry with Clinical Correlations, 4th edition by Thomas M Devlin
General Structure of Common Amino Acids
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?General structure of amino acids, group and a variable side chain
?Side chain determines: protein folding, binding to specific ligand and interaction
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with its environment
?Amino acids consists of a constant
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COOH (R is side chain)?At neutral pH, H N- protonated to H N+-, and ?COOH deprotonated to ?COO-
2
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3
Fig.4.2. Biochemistry. 4th edition by Donald Voet and Judith G. Voet
Amino-Acids Classification Based on Standard and Non-
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Standard Amino Acids
1. Standard amino-acids: Those 20 amino acids are encoded by universal
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genetic code2. Non-Standard amino-acids: Two amino acids incorporated into proteins by
unique synthetic mechanism
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?Selenocysteine: Incorporated when mRNA translated included SECIS
(selenocysteine insertion seq) element, causes the UGA codon to encode
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selenocysteine instead of stop codon)?Pyrrolysine: used by methanogenic archaea in enzyme that they use to produce
methane. It is coded for UAG stop codon.
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Standard amino acids
?All proteins are composed of the 20 "standard "amino acids.
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?Common central alpha ()-carbon atom bound to a carboxylic acid group, anamino group and a hydrogen atom are covalently bonded.
?They have a primary amino group and a carboxylic acid group substituent on the
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same carbon atom, with the exception of proline, (has a secondary amino group).
Fig.4.1. Biochemistry. 4th edition by Donald Voet and Judith G. Voet
How Proline gives conformational rigidity?
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?Proline classified as an imino acid, its -amine is a secondary amine with its a
nitrogen having two covalent bonds to carbon (to the -carbon and side chain
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carbon), rather than primary amine?Incorporation of amino nitrogen into a five membered ring constrains rotational
freedom around ?N -C
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-bond in proline to specific rotational angle, reduces
structural flexibility of polypeptide regions containing proline.
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Non-Standard Amino Acids?Selenocysteine, 21st protein L- amino acids
?Selenium atom replaces the sulfur of its elemental analog, cysteine
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?Selenocysteine is not the product of a posttranslational modification, but is inserted
directly into a growing polypeptide during translation.
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? Selenocysteine is charged on a special tRNA called tRNA Sec specific for UGA(STOP)codon inserted into growing polypeptide during translation
Other Classification of Amino Acids
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?Non-protein aa: Not naturally encoded by genetic code but found in free state asintermediates of metabolic pathway for standard aa: Ornithine and citrulline are
intermediates in urea biosynthesis.
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? Non -aa: -NH 2 group not attached to -carbon atom but some other carbon
atom. Ex. -aminobutyric acid (GABA) and -alanine.
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?Modified protein aa: Amino acids modified after they incorporated into protein.Proline and lysine undergo hydroxylation to become hydroxyproline and
Hydroxylysine. Essential for formation of mature collagen.
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AA Classified on Basis of Nutritional Requirement
?Essential amino acids: Not synthesised in the body and must be supplied in diet
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?Non-essential amino acids: Synthesized in body and there is no dietdependency for them
?Semi-essential amino acids: Not synthesised in the body in adequate amounts
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and requires dietary supplementation.
Amino-Acid Requirements of Humans
Table 28.1. Harper's Il ustrated Biochemistry 26th edition
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AA Classified on Basis of metabolic classification
?Ketogenic amino acids: Only two aa are ketogenic, ex. Lysine and leucine. They
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catabolically give intermediates convertible into acetyl-CoA or acetoacetyl-CoA?Glucogenic amino acids: Those aa give rise to intermediates of glycolysis or
Kreb's cycle convertible by gluconeogenesis into glucose. Ex. Arg, His etc.
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?Mixed amino acids: There are aa, carbon skeleton of which catabolized to
produce the glycolytic intermediates as well as acetyl-CoA derivatives. Ex. Phe,
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Try etc.Amino-Acids Classification Based on Side Chain Groups
?Based on type of functional group (R group) present amino acids are classified
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as: Aliphatic, aromatic, acidic, basic, acid amide, sulfur and cyclic amino acids.?Based on characteristic of functional group amino acids are classified as: polar
and non-polar amino acids.
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?Based on site of attachment of functional group. They are also classified as:
alpha, beta, gamma and delta amino acids.
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Amino Acids Classification based on hydrophobic and hydrophilic propertywww.khanacademy.org
Cont--
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Nonpolar/HydrophobicMethyl R group
Isopropyl R group
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Branching in isobutyl side chain on carbon of amino
acid
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Branching in isobutyl side chain on carbon of aminoacid
Table 3.1. Harper's Il ustrated Biochemistry 30 edition
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Cont--
Polar, uncharged-R group
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Hydroxymethyl R groupPolar, uncharged-R group
Secondary Alcohol structure
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Mentioned in amino acids with aromatic rings section
Polar, uncharged-R group
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Thiolmethyl/Sulfhydryl R groupNonpolar
Methyl ethyl thiol ether R group
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Cont--Negatively charged R group
-COOH R group
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Polar, Uncharged-R group
Negatively charged R group
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-COOH R groupPolar, Uncharged-R group
Cont--
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Positively charged R groups
Guanidinium R group
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-NH+3 R groupImidazolium R group
Cont--
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Mentioned in amino acids with basic groups sectionBenzene ring R group
Phenol R group
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Heterocyclic structure, indole R group
Imino group belongs to a five-member ring
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Function of Essential Amino acidsNon-polar amino acids:
1. Aromatic aa:
a) Phenylalanine: precursor for tyrosine, dopamine, nor-epinephrine, epinephrine and
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melanin.
?Genetic disorder phenylketonuria is the inability to metabolize phenylalanine because
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of a lack of phenylalanine hydroxylase.a) Tryptophan: precursor for neurotransmitter (serotonin), hormone (melatonin) and
vitamin niacin. Trp and Ty r residues anchoring membrane proteins within cel
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membrane.
?Fructose malabsorption causes improper absorption of Trp in intestine causes reduced
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level of Trp in blood.2. Aliphatic amino acids:
a) Alanine: Alanine synthesized from pyruvate and branched chain aa. It plays
an imp. role in glucose-alanine cycle between tissues and liver.
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?This cycle enables pyruvate and glutamate to be removed from muscle and
safely transported to liver.
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?Alteration in alanine cycle increase the level of ALT (Alanine transferases) whichlinked to the development of type I diabetes.
b) Valine: Essential for hematopoietic stem cel (HSC) self-renewal.
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?In sickle-cel disease, a single glutamic acid in -globin replaced with valine becausevaline is hydrophobic, whereas glutamic acid is hydrophilic, this change makes the Hb
prone to abnormal aggregation.
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c) Leucine: Primary metabolic end products of leucine metabolism are acetyl-CoA and
acetoacetate. It is also a imp ketogenic aa.
?Adipose and muscle tissue use leucine in the formation of sterols.
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?MSUD caused by deficiency of branched chain -keto acid dehydrogenase complexleading to build-up branched chain aa and their toxic product ketoacids present in blood
and urine.
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c) Isoleucine: diverse physiological functions, such as assisting wound healing,detoxification of nitrogenous wastes, stimulating immune function, and promoting
secretion of several hormones.
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3. Sulfur-containing aa:
a) Methionine: Substrate for other amino acids such as cysteine and taurine, versatile
compounds such as S-adenosyl methionine and antioxidant glutathione.
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?Homocysteine can be used to regenerate methionine or to form cysteine.
?Improper conversion of methionine can lead to atherosclerosis due to accumulation of
homocysteine.
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Polar uncharged aa:
1. Threonine: Its residue ssusceptible to numerous posttranslational
modifications.
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?The hydroxyl side-chain undergo O-linked glycosylation.
?Threonine residues undergo phosphorylation through the action of a threonine
kinase. In its phosphorylated form, it can be referred to as phosphothreonine. Its
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role in cell signal transduction and neural activity.
Polar Charged amino-acids:
1. Positive charge/Basic aa:
a) Histidine: precursor for histamine, an amine produced in the body necessary
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for inflammation.
?Histidine ammonia-lyase converts histidine into ammonia and urocanic acid.
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deficiency in this enzyme in rare metabolic disorder histidinemia.b) Lysine: Lysine can also contribute to protein stability as its -amino group
often participates in hydrogen bonding, salt bridges and covalent interactions to
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form a Schiff base.
?A second major role of lysine is in epigenetic regulation by means of histone
modification.
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?It plays a key role in other biological processes including; structural proteins of
connective tissues, calcium homeostasis and fatty-acid metabolism.
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?Due to a lack of lysine catabolism, the amino acid accumulates in plasma andpatients develop hyperlysinaemia.
Summary
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?Both -amino acids and non--amino acids occur in nature, but proteins aresynthesized using only L--amino acids.
?The R groups of amino acids determine their unique biochemical functions.
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?Amino acids are classified as basic, acidic, aromatic, aliphatic, or sulfur-
containing based on the composition and properties of their R groups.
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Interaction with studentsDistributed subtopics of today's lecture to students for participate in group discussion in
next lecture.
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THANK YOU