DOCSLIB.ORG

Types of Mutations (Table 15-1 on P. 464) II. Reverse Mutations

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Types of Mutations (Table 15-1 on P. 464) II. Reverse Mutations 3/7/02 Reminders: PT school presentation, 12:30, MO 157 Our faculty research interests, 12:30, MM#2 Quiz on Tues., Mar. 12 Types of mutations (Table 15-1 on p. 464) I. Forward mutation - single* base-pair substitution (* see frameshift mutations) · Transitions AT à GC; pur à pur; pyr à pyr · Transversion AT à CG; pur à pyr; pyr à pur · Silent mutation = Synonymous substitution - codon change, but no a.a. change (e.g. AGG à AGA are Arg) · Missense mutaion = Nonsynonymous substitution - any base change that causes an a.a. change · Neutral mutation - a.a. change, but no change in protein functionality · Null mutation - a.a. change leading to loss of function · Nonsense mutation - codon changed to a stop codon; most nonsense mutations are also null mutations · Frameshift mutation - insertion or deletion of one or more base pairs (not a multiple of three) within the translated portion of a gene causing the triplet reading frame to shift resulting in different a.a. from that point forward (i.e., downstream) or until chain termination. II. Reverse Mutations · Exact reversion - base pair change in the mutant type to the original wild type AAA forward à GAA reverse à AAA · Equivalent reversion - UCC (Ser) forward à UGC (Cys) reverse à AGC(Ser) CGC Arg, basicforward à CCC Pro, nonbasic reverse à CAC His, basic Another categorization of mutations · Spontaneous mutation - change that occurs naturally · Induced mutation - change that occurs following exposure to mutagenic agent How common are mutations? · Mutation rate = the number of mutations occurring in some unit of time · Mutation frequency = the frequency at which a specific kind of mutation (or mutant type) is found in a population of cells or individuals · In the example, only one mutation has occurred over seven cell divisions, therefore mutation rate is 1/7. Shouldn' t this be 1/3? · In the example, in the final population of 8 cells there are 2 mutants, therefore the mutation frequency is 2/8 Mechanisms of gene mutation Spontaneous mutaion (Replication errors) Tautomeric shift (base shifts to a different isomeric configuration with different pairing properties). This can result in a mispair. Examples: CG à C*A replication results in C*A and TA (transition) TA à T*G replication results in T*G and CG (transition) GC à G*T replication results in G*T and AT (transition) AT à A*C replication results in A*C and GC (transition) Transversion also may occur by mispairing of a pur with a pur or pyr with a pyr, but these are more rare. Frameshift mutation - seem to occur more often at repeated sequences (see Fig. 16-4) Spontaneous mutations (spontaneous DNA damage) Depurination - spontaneous loss of a purine (either A or G) off the DNA backbone. Repair enzymes available to fix this damage. However, if replication follows before repair occurs, a random nucleotide can be inserted across from the apurinic site resulting possibly in a mutation. Deamination - Spontaneous loss of the amine (-NH2) from cytosine or 5-methlycytosine. · C à U - deamination of cytosine creates uracil · 5MC à T - 5MC is simply a methylated form of C that has the pairing properties of C. Methylation is thought to play in role in regulating transcription. Deamination of 5MC creates T. Uracils are usually remove by a specific repair enzyme. This leaves an unpaired G. Another repair enzyme then inserts C. The net result of the cytosine deamination and repair restores the original sequence. But for the other deamination, T, of course, is not recognized as an error. Therefore, 5MC residues act as hot spots of mutation. (C à T transitions). Induced Mutations (base analogs) 5-BU and 2-AP · 5-BU is an analog of T. Once it pairs with C, it can frequently change to an isomer that mispairs with G. AT à GC or TA à CG unless it is ionized first then it is an analog of cytosine and causes GCà AT · 2-AP is an analog of A. Once it pairs with T, it can be protonated and mispair with C. AT à GC or TA à CG transition unless it is protonated first thereby becoming an analog of G and causing GCà AT transistion Induced Mutations (base altering agents) Alkylating agents - EMS and NG · EMS adds an ethyl group (and NG a methyl group) to guanine causing it to mispair with thymine. GC à AT or CG à TA transition (rarely causes AT à GC transition) HA (NH2OH) · HA hydroxylates cytosine causing it to mispair with adenine. GC à AT or CG à TA transitions only. NA · NA changes cytosine to uracil which mispairs with adenine. GC à AT or CG à TA transitions. · NA can also deaminates adenine to form HX which mispairs with cytosine. AT à GC or TA à CG transitions. Intercalating agents (proflavin, acridine orange, ICR compounds) These agents are planar polycyclic molecules that are about the same width of the double helix diameter. They can slip inbetween (intercalate) the paired bases at the center or the DNA molecule resulting in a insertion or deletion - frameshift mutation. Ethidium bromide is an intercalating agent, too..
Load more

Recommended publications
  • Evolutionary Origins of DNA Repair Pathways: Role of Oxygen Catastrophe in the Emergence of DNA Glycosylases
    cells Review Evolutionary Origins of DNA Repair Pathways: Role of Oxygen Catastrophe in the Emergence of DNA Glycosylases Paulina Prorok 1 , Inga R. Grin 2,3, Bakhyt T. Matkarimov 4, Alexander A. Ishchenko 5 , Jacques Laval 5, Dmitry O. Zharkov 2,3,* and Murat Saparbaev 5,* 1 Department of Biology, Technical University of Darmstadt, 64287 Darmstadt, Germany; [email protected] 2 SB RAS Institute of Chemical Biology and Fundamental Medicine, 8 Lavrentieva Ave., 630090 Novosibirsk, Russia; [email protected] 3 Center for Advanced Biomedical Research, Department of Natural Sciences, Novosibirsk State University, 2 Pirogova St., 630090 Novosibirsk, Russia 4 National Laboratory Astana, Nazarbayev University, Nur-Sultan 010000, Kazakhstan; [email protected] 5 Groupe «Mechanisms of DNA Repair and Carcinogenesis», Equipe Labellisée LIGUE 2016, CNRS UMR9019, Université Paris-Saclay, Gustave Roussy Cancer Campus, F-94805 Villejuif, France; [email protected] (A.A.I.); [email protected] (J.L.) * Correspondence: [email protected] (D.O.Z.); [email protected] (M.S.); Tel.: +7-(383)-3635187 (D.O.Z.); +33-(1)-42115404 (M.S.) Abstract: It was proposed that the last universal common ancestor (LUCA) evolved under high temperatures in an oxygen-free environment, similar to those found in deep-sea vents and on volcanic slopes. Therefore, spontaneous DNA decay, such as base loss and cytosine deamination, was the Citation: Prorok, P.; Grin, I.R.; major factor affecting LUCA’s genome integrity. Cosmic radiation due to Earth’s weak magnetic field Matkarimov, B.T.; Ishchenko, A.A.; and alkylating metabolic radicals added to these threats.
    [Show full text]
  • DNA Insertion Mutations Can Be Predicted by a Periodic Probability
    Research article DNA insertion mutations can be predicted by a periodic probability function Tatsuaki Tsuruyama1 1Department of Pathology, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan Running title: Probability prediction of mutation Correspondence to: Tatsuaki Tsuruyama Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan Tel.: +81-75-751-3488; Fax: +81-75-761-9591 E-mail: [email protected] 1 Abstract It is generally difficult to predict the positions of mutations in genomic DNA at the nucleotide level. Retroviral DNA insertion is one mode of mutation, resulting in host infections that are difficult to treat. This mutation process involves the integration of retroviral DNA into the host-infected cellular genomic DNA following the interaction between host DNA and a pre-integration complex consisting of retroviral DNA and integrase. Here, we report that retroviral insertion sites around a hotspot within the Zfp521 and N-myc genes can be predicted by a periodic function that is deduced using the diffraction lattice model. In conclusion, the mutagenesis process is described by a biophysical model for DNA–DNA interactions. Keywords: Insertion, mutagenesis, palindromic sequence, retroviral DNA 2 Text Introduction Extensive research has examined retroviral insertions to further our understanding of DNA mutations. Retrovirus-related diseases, including leukemia/lymphoma and AIDS, develop after retroviral genome insertion into the genomic DNA of the infected host cell. Retroviral DNA insertion is one of the modes of insertional mutation. After reverse-transcription of the retroviral genomic RNA into DNA, the retroviral DNA forms a pre-insertion complex (PIC) with the integrase enzyme, which catalyzes the insertion reaction.
    [Show full text]
  • DNA Sequence Insertion and Evolutionary Variation in Gene Regulation (Mobile Elements/Long Terminal Repeats/Alu Sequences/Factor-Binding Sites) Roy J
    Proc. Natl. Acad. Sci. USA Vol. 93, pp. 9374-9377, September 1996 Colloquium Paper This paper was presented at a colloquium entitled "Biology of Developmental Transcription Control, " organized by Eric H. Davidson, Roy J. Britten, and Gary Felsenfeld, held October 26-28, 1995, at the National Academy of Sciences in Irvine, CA. DNA sequence insertion and evolutionary variation in gene regulation (mobile elements/long terminal repeats/Alu sequences/factor-binding sites) RoY J. BRITrEN Division of Biology, California Institute of Technology, 101 Dahlia Avenue, Corona del Mar, CA 92625 ABSTRACT Current evidence on the long-term evolution- 3 and 4). Sequence change, obscuring the original structure, ary effect of insertion of sequence elements into gene regions has occurred in the long history, and the underlying rate of is reviewed, restricted to cases where a sequence derived from base substitution that is responsible is known (5). a past insertion participates in the regulation of expression of The requirements for a convincing example are: (i) that a useful gene. Ten such examples in eukaryotes demonstrate there be a trace of a known class of elements present in gene that segments of repetitive DNA or mobile elements have been region; (ii) that there is evidence that it has been there long inserted in the past in gene regions, have been preserved, enough to not just be a transient mutation; (iii) that some sometimes modified by selection, and now affect control of sequence residue of the mobile element or repeat participates transcription ofthe adjacent gene. Included are only examples in regulation of expression of the gene; (iv) that the gene have in which transcription control was modified by the insert.
    [Show full text]
  • Genetic Analysis of the Transition from Wild to Domesticated Cotton (G
    bioRxiv preprint doi: https://doi.org/10.1101/616763; this version posted April 23, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Genetic analysis of the transition from wild to domesticated cotton (G. hirsutum) Corrinne E. Grover1, Mi-Jeong Yoo1,a, Michael A. Gore2, David B. Harker3,b, Robert L. Byers3, Alexander E. Lipka4, Guanjing Hu1, Daojun Yuan1, Justin L. Conover1, Joshua A. Udall3,c, Andrew H. Paterson5, and Jonathan F. Wendel1 1Department of Ecology, Evolution and Organismal Biology, Iowa State University, Ames, IA 50011 2Plant Breeding and Genetics Section, School of Integrative Plant Science, Cornell University, Ithaca, NY 14853 3Plant and Wildlife Science Department, Brigham Young University, Provo, UT 84602 4Department of Crop Sciences, University of Illinois, Urbana, IL 61801 5Plant Genome Mapping Laboratory, University of Georgia, Athens, GA 30602 acurrent address: Department of Biology, University of Florida, Gainesville, FL 32611 bcurrent address: Department of Dermatology, The University of Texas Southwestern Medical Center, Dallas, TX 75390 ccurrent address: Southern Plains Agricultural Research Center, USDA-ARS, College Station, TX, 77845- 4988 Corresponding Author: Jonathan F. Wendel ([email protected]) Data Availability: All data are available via figshare (https://figshare.com/projects/Genetic_analysis_of_the_transition_from_wild_to_domesticated_cotton_G _hirsutum_QTL/62693) and GitHub (https://github.com/Wendellab/QTL_TxMx). Keywords: QTL, domestication, Gossypium hirsutum, cotton Summary: An F2 population between truly wild and domesticated cotton was used to identify QTL associated with selection under domestication.
    [Show full text]
  • The Mutability and Repair of DNA
    B.Sc (Hons) Microbiology (CBCS Structure) C-7: Molecular Biology Unit 2: Replication of DNA The Mutability and Repair of DNA Dr. Rakesh Kumar Gupta Department of Microbiology Ram Lal Anand College New Delhi - 110021 Reference – Molecular Biology of the Gene (6th Edition) by Watson et. al. Pearson education, Inc Principles of Genetics (8th Edition) by D. Peter Snustad, D. Snustad, Eldon Gardner, and Michael J. Simmons, Wiley publications Replication errors and their repair The Nature of Mutations: • Transitions: A kind of the simplest mutation which is pyrimidine-to-pyrimidine and purine-to- purine substitutions such as T to C and A to G • Transversions: The other kind of mutation which are pyrimidine-to-purine and purine-to- pyrimidine substitutions such as T to A or G and ATransitions to C or T. Transversions 8 types 4 types Synonymous substitution Non synonymous substitution • Point mutations: Mutations that alter a single nucleotide Other kinds of mutations (which cause more drastic changes in DNA): • Insertions • Deletions • Gross rearrangements of Thesechromosome mutations might be caused by insertion by transposon or by aberrant action of cellular recombination processes. Mutation • Substitution, deletion, or insertion of a base pair. • Chromosomal deletion, insertion, or rearrangement. Somatic mutations occur in somatic cells and only affect the individual in which the mutation arises. Germ-line mutations alter gametes and passed to the next generation. Mutations are quantified in two ways: 1. Mutation rate = probability of a particular type of mutation per unit time (or generation). 2. Mutation frequency = number of times a particular mutation occurs in a population of cells or individuals.
    [Show full text]
  • Genetic Causes.Pdf
    1 September 2015 Genetic causes of childhood apraxia of speech: Case‐based introduction to DNA, inheritance, and clinical management Beate Peter, Ph.D., CCC‐SLP Assistant Professor Dpt. of Speech & Hearing Science Arizona State University Adjunct Assistant Professor AG Dpt. of Communication Sciences & Disorders ATAGCT Saint Louis University T TAGCT Affiliate Assistant Professor Dpt. of Speech & Hearing Sciences University of Washington 1 Disclosure Statement Disclosure Statement Dr. Peter is co‐editor of a textbook on speech development and disorders (B. Peter & A. MacLeod, Eds., 2013), for which she may receive royalty payments. If she shares information about her ongoing research study, this may result in referrals of potential research participants. She has no financial interest or related personal interest of bias in any organization whose products or services are described, reviewed, evaluated or compared in the presentation. 2 Agenda Topic Concepts Why we should care about genetics. Case 1: A sporadic case of CAS who is missing a • Cell, nucleus, chromosomes, genes gene. Introduction to the language of genetics • From genes to proteins • CAS can result when a piece of DNA is deleted or duplicated Case 2: A multigenerational family with CAS • How the FOXP2 gene was discovered and why research in genetics of speech and language disorders is challenging • Pathways from genes to proteins to brain/muscle to speech disorder Case 3: One family's quest for answers • Interprofessional teams, genetic counselors, medical geneticists, research institutes • Early signs of CAS, parent education, early intervention • What about genetic testing? Q&A 3 “Genetic Causes of CAS: Case-Based Introduction to DNA, Inheritance and Clinical Management,” Presented by: Beate Peter, PhD, CCC-SLP, September 29, 2015, Sponsored by: CASANA 2 Why should you care about genetics? 4 If you are a parent of a child with childhood apraxia of speech … 5 When she was in preschool, He doesn’t have any friends.
    [Show full text]
  • Insertion Element (IS1 Insertion Sequence/Chloramphenicol Resistance Transposon Tn9/Integrative Recombination) L
    Proc. Nati. Acad. Sci. USA Vol. 75, No. 3, pp. 1490-1494, March 1978 Genetics Chromosomal integration of phage X by means of a DNA insertion element (IS1 insertion sequence/chloramphenicol resistance transposon Tn9/integrative recombination) L. A. MACHATTIE AND J. A. SHAPIRO Department of Microbiology, University of Chicago, Chicago, Illinois 60637 Communicated by Albert Dorfman, January 10, 1978 ABSTRACT Phage Xcamll2, which contains the chlor- carries a deletion of the gal-attB-bio region of the Escherichia amphenicol resistance transposon Tn9 and has a deletion of attP coil chromosome. MGBO is a gal+bio+ transductant of and the int gene, will lysogenize Escherichia coli K-12. Pro- phage integration occurs at different chromosomal sites, in- MADO. MS6 is a galE indicator for detection of XgalE + T- cluding lacYand maiB, but not at attB. All Xcamll2 prophages transducing particles and S1653 is a gal deletion strain for de- are excised from the chromosome after induction but with tection of Xgal + particles (3). Strain 200PS is a thi lacY strain various efficiencies for different locations. Heteroduplex from the Pasteur collection. Strain QL carries a complete lac analysis of XplacZ transducing phages isolated from a lacY:: deletion, strain X9003 carries the nonpolar M15 lacZ deletion, Xcamll2 prophage reveals an insertion sequence 1 (IS1) element and either will serve as indicator for XplacZ phage in a blue at theloint of viral and chromosomal DNA. Two lines of evi- dencekdicate that Xcamll2 encodes an excision activity that plaque assay (8). recognizes the ISI element: (i) prophage derepression increases Media. Our basic minimal medium and complete TYE the frequency of excision from IacYto yield lac+ revertants, and medium have been described (9).
    [Show full text]
  • Mutation by Dr. Ty C.M. Hoffman
    Mutation by Dr. Ty C.M. Hoffman Slide 1 Transcription features a one-to-one correspondence between DNA nucleotides in the gene and RNA nucleotides in the RNA transcript. However, the four nucleotide types used in RNA are insufficient to individually specify all twenty biological amino acids during translation. Instead, a sequence of three mRNA nucleotides (collectively called a codon) specifies a single amino acid. Since there are three nucleotide positions within a codon, and each position can be occupied by any of four types of nucleotide, there are sixty-four possible codons. This is more than enough to specify the twenty biological amino acids. Slide 2 The genetic code is universal in that all organisms (with very few exceptions) use the same code for specifying amino acids with mRNA codons. The genetic code is redundant in that more than one codon can specify the same amino acid. This is because there are more types of codons than there are types of amino acids used by organisms. The genetic code is not ambiguous, however, because each codon always specifies the same amino acid. Four of the codons serve special functions. One operates as a start codon (signaling initiation of translation), and three codons operate as stop codons (signaling the termination of translation). Slide 3 Mutation is a random change in the DNA sequence of nucleotides. Mutation can be purely accidental (by a mistake made during DNA replication), or mutation can result from exposure of DNA to a mutagen (something that causes mutation). Mutations can be classified into two major types: • Base-pair substitutions do not change the number of nucleotides in the DNA, because one base pair is substituted for another.
    [Show full text]
  • Bio 102 Practice Problems Genetic Code and Mutation
    Bio 102 Practice Problems Genetic Code and Mutation Multiple choice: Unless otherwise directed, circle the one best answer: 1. Choose the one best answer: Beadle and Tatum mutagenized Neurospora to find strains that required arginine to live. Based on the classification of their mutants, they concluded that: A. one gene corresponds to one protein. B. DNA is the genetic material. C. "inborn errors of metabolism" were responsible for many diseases. D. DNA replication is semi-conservative. E. protein cannot be the genetic material. 2. Choose the one best answer. Which one of the following is NOT part of the definition of a gene? A. A physical unit of heredity B. Encodes a protein C. Segement of a chromosome D. Responsible for an inherited characteristic E. May be linked to other genes 3. A mutation converts an AGA codon to a TGA codon (in DNA). This mutation is a: A. Termination mutation B. Missense mutation C. Frameshift mutation D. Nonsense mutation E. Non-coding mutation 4. Beadle and Tatum performed a series of complex experiments that led to the idea that one gene encodes one enzyme. Which one of the following statements does not describe their experiments? A. They deduced the metabolic pathway for the synthesis of an amino acid. B. Many different auxotrophic mutants of Neurospora were isolated. C. Cells unable to make arginine cannot survive on minimal media. D. Some mutant cells could survive on minimal media if they were provided with citrulline or ornithine. E. Homogentisic acid accumulates and is excreted in the urine of diseased individuals. 5.
    [Show full text]
  • Coincident Two Mutations and One Single Nucleotide Polymorphism of the PTCH1 Gene in a Family with Naevoid Basal Cell Carcinoma Syndrome
    Letters to the Editor 635 Coincident Two Mutations and One Single Nucleotide Polymorphism of the PTCH1 Gene in a Family with Naevoid Basal Cell Carcinoma Syndrome Shoko Abe1, Kenji Kabashima1*, Jun-ichi Sakabe1, Takatoshi Shimauchi1, Zhang Yan2, Tetsuji Okamoto2 and Yoshiki Tokura1 1Department of Dermatology, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, and 2Department of Molecular Oral Medicine and Maxillofacial Surgery 1, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. E-mail: [email protected] Accepted May 7, 2008. Sir, at nucleotide position 667 within exon 3 and an intervening se- Naevoid basal cell carcinoma syndrome (NBCCS, OMIM quence (IVS)16 -3T > C, and a SNP; IVS10 -8T > C, were detected in all three cases. A deletion of AGAC causes a frameshift and a #109400), also called Gorlin’s syndrome, is an autosomal subsequent stop codon in exon 3, which prematurely truncates dominant disease that affects about 1 in 60,000 indivi- the protein (Fig. 1a). In addition, the IVS16 -3T > C could lead duals (1, 2). NBCCS is associated with various skeletal to an aberrant splicing and truncation of PTCH1 (10–12). and neurocutaneous abnormalities. Major manifestations To detect the expression level of PTCH1 protein in the skin, are multiple basal cell carcinomas (BCCs), odontogenic an immunohistochemical study was performed using goat poly- clonal anti-PTCH1 antibody (G-19; Santa Cruz Biotechnology, keratocysts, palmoplantar dyskeratotic pits and intra- Santa Cruz, CA, USA). Enzyme reactions were developed with cranial calcification (3). In addition, rib and vertebral conventional substrates for diamino-benzidine (Sigma, St Louis, malformations, epidermal cysts, macrocephaly, facial MO, USA) (13).
    [Show full text]
  • Antibiotic Resistance by High-Level Intrinsic Suppression of a Frameshift Mutation in an Essential Gene
    Antibiotic resistance by high-level intrinsic suppression of a frameshift mutation in an essential gene Douglas L. Husebya, Gerrit Brandisa, Lisa Praski Alzrigata, and Diarmaid Hughesa,1 aDepartment of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala University, Uppsala SE-751 23, Sweden Edited by Sankar Adhya, National Institutes of Health, National Cancer Institute, Bethesda, MD, and approved January 4, 2020 (received for review November 5, 2019) A fundamental feature of life is that ribosomes read the genetic (unlikely if the DNA sequence analysis was done properly), that the code in messenger RNA (mRNA) as triplets of nucleotides in a mutants carry frameshift suppressor mutations (15–17), or that the single reading frame. Mutations that shift the reading frame gen- mRNA contains sequence elements that promote a high level of ri- erally cause gene inactivation and in essential genes cause loss of bosomal shifting into the correct reading frame to support cell viability viability. Here we report and characterize a +1-nt frameshift mutation, (10). Interest in understanding these mutations goes beyond Mtb and centrally located in rpoB, an essential gene encoding the beta-subunit concerns more generally the potential for rescue of mutants that ac- of RNA polymerase. Mutant Escherichia coli carrying this mutation are quire a frameshift mutation in any essential gene. We addressed this viable and highly resistant to rifampicin. Genetic and proteomic exper- by isolating a mutant of Escherichia coli carrying a frameshift mutation iments reveal a very high rate (5%) of spontaneous frameshift suppres- in rpoB and experimentally dissecting its genotype and phenotypes. sion occurring on a heptanucleotide sequence downstream of the mutation.
    [Show full text]
  • Lecture: 28 TRANSAMINATION, DEAMINATION and DECARBOXYLATION
    Lecture: 28 TRANSAMINATION, DEAMINATION AND DECARBOXYLATION Protein metabolism is a key physiological process in all forms of life. Proteins are converted to amino acids and then catabolised. The complete hydrolysis of a polypeptide requires mixture of peptidases because individual peptidases do not cleave all peptide bonds. Both exopeptidases and endopeptidases are required for complete conversion of protein to amino acids. Amino acid metabolism The amino acids not only function as energy metabolites but also used as precursors of many physiologically important compounds such as heme, bioactive amines, small peptides, nucleotides and nucleotide coenzymes. In normal human beings about 90% of the energy requirement is met by oxidation of carbohydrates and fats. The remaining 10% comes from oxidation of the carbon skeleton of amino acids. Since the 20 common protein amino acids are distinctive in terms of their carbon skeletons, amino acids require unique degradative pathway. The degradation of the carbon skeletons of 20 amino acids converges to just seven metabolic intermediates namely. i. Pyruvate ii. Acetyl CoA iii. Acetoacetyl CoA iv. -Ketoglutarate v. Succinyl CoA vi. Fumarate vii. Oxaloacetate Pyruvate, -ketoglutarate, succinyl CoA, fumarate and oxaloacetate can serve as precursors for glucose synthesis through gluconeogenesis.Amino acids giving rise to these intermediates are termed as glucogenic. Those amino acids degraded to yield acetyl CoA or acetoacetate are termed ketogenic since these compounds are used to synthesize ketone bodies. Some amino acids are both glucogenic and ketogenic (For example, phenylalanine, tyrosine, tryptophan and threonine. Catabolism of amino acids The important reaction commonly employed in the breakdown of an amino acid is always the removal of its -amino group.
    [Show full text]