MBBS Biochemistry Passing Series
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This document provides information about a biochemistry textbook titled "Biochemistry Passing MBBS Series" by Karthikeyan Pethusamy. The key details include that it is a concise, colorful, and conceptually illustrated textbook following the Competency-Based Medical Education curriculum. It contains over 500 diagrams, tables, and quick revision points. The purchase of the book provides 365 days of free access to a companion Android app with additional learning features. The author's social media pages and YouTube channel are also provided for further learning resources.
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MBBS Biochemistry Passing Series
- 1. Biochemistry Passing MBBS Series Karthikeyan Pethusamy Special Features Ÿ Concise, colorful and conceptual synopsis Ÿ 500+ fully-illustrated diagrams, lowcharts and tables Ÿ 600+ Quick revision points, MCQs, SAQs and direct one- liner type questions at the end of each and every chapter Ÿ Free companion android app As per the Competency-Based Medical Education (CBME) Curriculum (2019) A clinically-oriented approach to biochemistry to strengthen your conceptual understanding First fully-colored exam-oriented manual on the subject with all new changes as per the New Curriculum for Undergraduates As per the Competency-Based Medical Education (CBME) Curriculum (2019)
- 2. Purchase of this book gives you 365-days of free access to the android with many useful features. 1) Installation - Go to Google Play store and search for the app (or) Simply Scan the given QR code 2) Sign up - Fill your name and a valid email ID. Enter the 6-digit alphanumeric scratch code 3) Enjoy Biochemistry - Learn Biochemistry through chapter-wise features—Outline, High-Yield Points, MCQs, SAQs and YouTube video lectures 4) Get your doubts clari ied - You can ask doubt any time through app and get it clari ied Good News! How to make use of the app? Author's Facebook Page: facebook.com/doctorkarthi Author's YouTube channel: youtube.com/c/KarthikeyanPethusamy Gently scratch the panel to access your 6-digit code.
- 3. PREFACE I am glad to inform you that the purchase of this book gives you advertisement-free access to my android app “Biochemistry with Dr Karthi”. In the app, you will get the explanations for multiple-choice questions. You will also be able to watch topic-wise lectures. This app is a portal for you to contact me and get your doubts clarified. I am glad that you continue to read the preface. Let me tell you why I have written this book. Compared to the Biochemistry I studied during my first year of MBBS, a present first-year student is required to learn a myriad of details. So, it is humanly impossible to revise the subject before any exam, be it qualifying or competitive. Therefore, I have decided to come up with a concise book that will be of great help as it is based on the new curriculum. I assure you that the content of this book is on par with the Indian as well as the International curriculum. Dear Friends, I have referred to the list of MCI competencies and ensured that this book covers almost all of them. To keep the book concise, I have deliberately skipped physiology topics, like immunity, muscle contraction, digestion and absorption. If you want me to cover any other topic, let me know through the android app or YouTube channel. I will make a video and give a handout. I made it a point to write this book only when I was in a peaceful and pleasant state of mind. I have spent the best hours of my life writing this book. I hope learning Biochemistry will be one of the joyful times of your life. I am delighted to bring you this competency-based, concise, colorful, conceptual yet exam-oriented book. This book is the culmination of my seven years of faithful study of the Medical Biochemistry. I can say for sure that I have put my best efforts in bringing out this book. So, you can put your trust in this book. I gladly welcome comments, suggestions, corrections and constructive criticism. Karthikeyan Pethusamy
- 4. Medical Council of India (MCI) has laid down a set of competency goals for the Indian medical graduates1 . I have tried my best to incorporate all these goals in this book. MCI recommendations Actions taken yy Obtaining competencies recommended yy Competencies achieved are given at the end of every chapter. yy Demonstrate the ability to perform an objective self-assessment of knowledge yy Self-assessment questions are given at the end of every chapter. yy The explanations for the MCQs are given in the companion Android app. yy Demonstrate ability to apply newly- gained knowledge or skills to the care of the patient yy Biochemical basis of 170 diseases has been given. yy Mechanism of action of 70 drugs given. yy Horizontal integration yy Topics, like karyotyping, plasma proteins are discussed with Biochemistry point of view for the horizontal integration. yy I recommend the students to read topics, like digestion and muscle contraction from physiology books. yy Vertical integration yy Harrison’s Corner and Clinical Correlation boxes are given to help in vertical integration. yy Case-based discussion in an appropriate format ensuring that elements in the same phase (horizontal) and from other phases are addressed yy Clinical Case-based Questions are given at the end of appropriate chapters. yy Case discussion video lectures are given in the Android app yy To be familiar with biomedical waste disposal yy Biomedical Waste Management has been explained in detail in Chapter 46. Definition of competency:“An observable ability of a health professional, integrating multiple components such as knowledge, skills, values and attitudes”2 . REFERENCES 1. Medical Council of India, Regulations on Graduate Medical Education, 1997 (Amended up to May, 2018), 2018, pg 6-8. 2. Medical Council of India, Competency-based Undergraduate Curriculum for the Indian Medical Graduate, 2018. Vol. 1; pg 38. COMPLIANCE TO THE NEW UG CURRICULUM
- 5. CONTENTS SECTION I: FUNDAMENTAL CONCEPTS OF BIOCHEMISTRY CHAPTER 1 Chemistry of Amino Acids 3–15 CHAPTER 2 Protein Structure 16–26 CHAPTER 3 Hemoglobin and Myoglobin 27–43 CHAPTER 4 Bioenergetics 44–50 CHAPTER 5 Enzymology 51–73 CHAPTER 6 Biological Oxidation and Electron Transport Chain 74–87 CHAPTER 7 Tricarboxylic Acid (TCA) Cycle 88–96 SECTION II: INTERMEDIARY METABOLISM CHAPTER 8 Introduction to Metabolism 99–102 CHAPTER 9 Chemistry of Carbohydrates 103–115 CHAPTER 10 Carbohydrate Metabolism 116–174 10.1 Introduction 116–118 10.2 Glycolysis 119–132 10.3 Gluconeogenesis 133–140 10.4 Glycogen Metabolism 141–151 10.5 Other Pathways for Oxidation of Glucose 152–158 10.6 Metabolism of Other Sugars 159–164 10.7 Regulation of Blood Glucose 165–174
- 6. xxvi Contents CHAPTER 11 Amino Acid Metabolism 175–231 11.1 Disposal of Amino Group and Urea Cycle 175–187 11.2 Synthesis of Nonessential Amino Acids 188–190 11.3 Fate of Carbon Skeleton 191–193 11.4 Special Products 194–202 11.5 One-carbon Metabolism 203–206 11.6 Inborn Errors of Amino Acid Metabolism 207–220 11.7 Heme Metabolism 221–231 CHAPTER 12 Chemistry of Lipids 232–247 CHAPTER 13 Lipid Metabolism 248–307 13.1 Fatty Acid Oxidation 248–256 13.2 Ketogenesis and Utilization of Ketone Bodies 257–263 13.3 Fatty Acid Synthesis 264–272 13.4 Metabolism of Cholesterol 273–280 13.5 Lipoproteins 281–295 13.6 Acylglycerols and Phospholipids Metabolism 296–301 13.7 Eicosanoids 302–307 CHAPTER 14 Metabolism of Alcohol 308–312 CHAPTER 15 Nucleotide Chemistry and Metabolism 313–333 CHAPTER 16 Integration of Metabolism 334–344 CHAPTER 17 Metabolism of Xenobiotics/Biotransformation Reactions 345–349 SECTION III: MOLECULAR BIOLOGY CHAPTER 18 Nucleic Acids: Introduction 353–363 CHAPTER 19 Organization of DNA 364–372 CHAPTER 20 Human Genome 373–380
- 7. xxvii Contents CHAPTER 21 DNA Replication and Repair 381–399 CHAPTER 22 Polymerase Chain Reaction 400–407 CHAPTER 23 Transcription 408–421 CHAPTER 24 Genetic Code 422–427 CHAPTER 25 Translation 428–442 CHAPTER 26 Protein Targeting 443–446 CHAPTER 27 Regulation of Gene Expression 447–458 CHAPTER 28 Recombinant DNA Technology and Molecular Techniques 459–471 CHAPTER 29 Stem Cells and Gene Therapy 472–477 CHAPTER 30 Medical Genetics 478–484 CHAPTER 31 Cancer Biology 485–496 SECTION IV: NUTRITION CHAPTER 32 General Principles of Nutrition and Macronutrients 499–509 CHAPTER 33 Micronutrients: Vitamins 510–532 CHAPTER 34 Micronutrients: Minerals 533–545 SECTION V: SPECIAL TOPICS CHAPTER 35 Plasma Proteins 549–557
- 8. xxviii Contents CHAPTER 36 Cell, Cell Membrane and Cytoskeleton 558–570 CHAPTER 37 Physical Chemistry and Acid-Base 571–582 CHAPTER 38 Cell-Signaling 583–590 CHAPTER 39 Free Radicals and Antioxidants 591–596 CHAPTER 40 Water and Electrolytes 597–602 CHAPTER 41 Glycoproteins and Proteoglycans 603–613 CHAPTER 42 Extracellular Matrix 614–623 CHAPTER 43 Tools of Proteomics 624–637 CHAPTER 44 Clinical Enzymology 638–646 CHAPTER 45 Organ Function Tests 647–653 CHAPTER 46 Practical Biochemistry 654–663 SECTION VI: REVIEW Appendix (Review) 667–672 � Named Reactions, Cycles and Pathways, Molecules 667 � Pioneers of Biochemistry 668 � The Most Common Genetic Disorders 669 � Regulatory/Rate Limiting Steps of Metabolic Pathways 671 � The First in History 672 � Biochemical Tests 672
- 9. KEY CONTENTS As per the recommendation of Medical Council of India, “The knowledge acquired in biochemistry should help the students to integrate molecular events with structure and function of the human body in health and disease1 .” So, I have given the biochemical basis of many common as well as uncommon diseases inside the book. Here is an alphabetical list. The page numbers on which you can find them in the book are as follows: yy Abetalipoproteinemia 287 yy Achondroplasia 425 yy Acrodermatitis enteropathica 541 yy Acute intermittent porphyria 224 yy Adenosine deaminase deficiency 323 yy Albinism 200 yy Albright’s hereditary osteodystrophy 483 yy Alkaptonuria 215 yy Alport syndrome 618 yy Alzheimer’s disease 440 yy Andersen disease 147 yy Angelman syndrome 483 yy Antibiotic-associated diarrhoea 278 yy Antiphospholipid antibody syndrome 241 yy Argininemia 181 yy Argininosuccinic aciduria 181 yy Aspirin-induced asthma 305 yy Barth syndrome 241 yy Beckwith-Wiedemann syndrome 483 yy Beriberi 518 yy Carnitine deficiency 253 yy Celiac disease 506 yy Cholestatic (obstructive) Jaundice 228 yy Chronic myeloid leukemia 487 yy Citrullinemia 181 yy Cori-Forbe disease 147 yy Crigler-Najjar syndrome 229 yy Cystic fibrosis 439 yy Cystinosis 217 yy Cystinuria 216 yy Danon’s disease 147 yy Diabetes insipidus 566 yy Diabetes mellitus 170 yy Diabetic cataract 159 yy Diabetic ketoacidosis 261 yy Dicarboxylic aciduria 216 yy Disorders of the urea cycle 181 yy DOPA-responsive dystonia 217 yy Drummond syndrome 216 yy Dubin-Johnson syndrome 229 yy Ehlers-Danlos syndrome 618 yy Endemic ascites 507 yy Epidemic dropsy 507 yy Essential fructosuria 161 yy Essential pentosuria 157 yy Fabry’s disease 299 yy Familial hypercholesterolemia 291 yy Familial hypertriglyceridemia 291 yy Familial chylomicronaemia 291 yy Familial combined hyperlipidemia 291 yy Familial Dysbetalipoproteinemia 291 yy Fanconi Bickel syndrome 116 yy Farber’s disease 299 yy Fish-eye disease 292 yy Fluorosis 543 yy Fragile X syndrome 376 yy Friedreich’s ataxia 376 yy Fructose-induced Hypertriglyceridemia 162 yy G6PD deficiency 155 yy Galactosemia 163 yy Gaucher’s disease 299 yy Gilbert syndrome 229, 425 yy Glutaric acidemia type I 217 yy Gout 323 yy Hartnup disease 216 yy Hawkinsinuria 217 yy Hemorrhagic disease of new born 515 yy Hepatic encephalopathy 179 yy Hereditary fructose intolerance 161 yy Hereditary nonpolyposis carcinoma of the colon 394 yy HHH syndrome 181 yy High anion gap acidosis 575 yy Homocystinuria 210 yy Hunter syndrome 610 yy Huntington’s disease 376, 439 yy Hurler syndrome 610 yy Hyperlipoproteinemias 291 yy Hypolipoproteinemias 291 yy I-cell disease 445 yy Imerslund-grasbeck syndrome 528 yy Iminoglycinuria 216 yy Ischemia-reperfusion injury 335 yy Isovaleric acidemia 217 yy Jamaican vomiting sickness 253 yy Kartagener syndrome 563 BIOCHEMICAL BASIS OF DISEASES
- 10. xxx KeyContents yy Kashin–Beck disease 542 yy Kelley-Seegmiller syndrome 327 yy Kennedy disease 376 yy Kernicterus 229 yy Keshan disease 542 yy Krabbe’s disease 299 yy Kwashiorkor 507 yy Lactose intolerance 504 yy Latent autoimmune diabetes in adults 171 yy Lathyrism 507 yy Lesch-Nyhan syndrome 325 yy Li-Fraumeni syndrome 425, 485 yy Lysinuric protein intolerance 216 yy Lysosomal storage disorders 299 yy Maple syrup urine disease 212 yy Marasmus 507 yy Marfan syndrome 620 yy Maturity-onset diabetes of the young 171 yy McArdle disease 147 yy Medium-Chain Acyl-CoA Dehydrogenase deficiency 254 yy MELAS 84 yy Menkes disease 540 yy Metabolic syndrome 341, 342 yy Metachromatic leukodystrophy 299 yy Methemoglobinemia 34 yy Methylmalonic acidemia 217 yy Multiple carboxylase deficiency 523 yy Multiple myeloma 553 yy Multiple sulfatase deficiency 299 yy Myotonic dystrophy 376 yy Neonatal adrenoleukodystrophy 254 yy Nephrotic syndrome 610 yy Neuromyelitis optica 566 yy Niemann-pick disease 299 yy Nonketotic hyperglycinemia 208 yy Normal anion gap acidosis 575 yy Norum’s disease 289 yy Nucleotide repeat disorders 376 yy Oasthouse syndrome 216 yy Orotic aciduria 326 yy Paracetamol poisoning 348 yy Paroxysmal nocturnal hemoglobinuria 607 yy Pellagra 518, 521 yy Phenylketonuria 207, 215 yy Phrynoderma 235 yy Physiological jaundice of newborn 229 yy Plumboporphyria 225 yy Pompe disease 147 yy Porphyrias 223 yy Prader-Willi syndrome 483 yy Primary hyperlipoproteinemias 291 yy Primary hyperoxaluria 208 yy Prion disease 439 yy Procollagen suicide in osteogenesis imperfecta 479 yy Propionic acidemia 217 yy Protein energy malnutrition 506 yy Pseudopseudo hypoparathyroidism 483 yy Refsum’s disease 254 yy Respiratory distress syndrome 241 yy Rotor syndrome 229 yy Russell-Silver syndrome 483 yy Sandhoff disease 299 yy Scurvy 520 yy Selenosis 542 yy Sickle cell disease 38 yy Smoking and emphysema 551 yy Steatorrhea 505 yy Stiff person syndrome 198 yy Tangier disease 294 yy Tarui’disease 147 yy Tay-Sachs disease 299 yy Thalassemia 39 yy Transient neonatal diabetes 483 yy Trehalose intolerance 505 yy Type 1 Hyperammonemia 181 yy Type 2 Hyperammonemia 181 yy Tyrosinemia type I 216 yy Tyrosinemia type II/Richner- Hanhart syndrome 216 yy Vit A toxicity 514 yy Von Gierke disease 147 yy William syndrome 619 yy Wilson’s disease 540 yy Xeroderma pigmentosum 395 yy Zellweger syndrome 254 MECHANISM OF ACTION OF DRUGS, POISONS AND TOXIN As per the MCI recommendation “The broad goal of the teaching of undergraduate students in biochemistry is to make them understand the scientific basis of the life processes at the molecular level and to orient them toward the application of the knowledge acquired in solving clinical problems2 .” yy α-amanitin 419 yy 2,4 dinitrophenol 82 yy 5-fluorouracil 204 yy Abacavir 329 yy Actinomycin 418 yy Acyclovir 330 yy Aflatoxin 347 yy Allopurinol 324 yy Arsenate 127 yy Arsenite 93 yy Asparaginase 645 yy Beta oxalyl amino alanine 507
- 11. xxxi KeyContents yy Bortezomib 183 yy British anti-lewisite 5 yy Caffeine 328 yy Cetirizine 199 yy Cholera toxin 588 yy Cholestyramine 287 yy Cyanide 82 yy Cycloheximide 437 yy Danaparoid 609 yy Didanosine 329 yy Digoxin 111 yy Diphtheria toxin 437 yy Disulfiram 311 yy Eflornithine 197 yy Eliglustat 300 yy Eteplirsen 476 yy Evolocumab 287 yy Ezetimibe 287 yy Febuxostat 324 yy Fibrates 287 yy Finasteride 644 yy Fomepizole 311 yy Fomivirsen 476 yy Gabapentin 198 yy Gliflozin 117 yy Gramicidin A 82 yy Heparin 609 yy Hydroxyurea 322 yy Idursulfase alpha 611 yy Imatinib 488 yy Isotretinoin 514 yy Kayexalate 599 yy Lactulose 179 yy Laronidase 611 yy Leflunomide 328 yy Lomitapide 287 yy Methotrexate 204, 328, 493 yy Methylxanthines 328 yy Miglustat 300 yy Mipomersen 287, 476 yy N-acetyl cysteine 348 yy Niacin 287 yy Nitroglycerin 196 yy NSAIDs 304 yy Oseltamivir 110 yy Ouabain 111 yy Pertussis toxin 588 yy Phenylbutyrate 182 yy Phlorizin 116 yy Probenecid 324 yy Proguanil 328 yy Propylthiouracil 644 yy Puromycin 437 yy Pyrrolizidine 507 yy Ranitidine 199 yy Rasburicase 325, 645 yy Ricin 437 yy Rifampicin 418 yy Sanguinarine 507 yy Sildenafil (Viagra) 196 yy Sodium benzoate 182 yy Statins 274 yy Streptokinase 645 yy Sulphonylurea 167 yy Tetracycline 437 yy Theobromine 328 yy Theophylline 328 yy Tretinoin 514 yy Trimethoprim 328 yy Urokinase 645 yy Zanamivir 110 TECHNIQUES AND TESTS yy Affinity chromatography 630 yy Ames test 490 yy Apt test 33 yy Arterial blood gas analysis 576 yy cDNA synthesis 403 yy Chromatin immunoprecipitation 469 yy Chromatography 628 yy Colorimetry 655 yy CRISPR/Cas9 system 396, 469 yy DNA electrophoresis 355 yy DNA fingerprinting 467 yy DNA footprinting 469 yy DNA library 460 yy DNA sequencing 467 yy Electrophoresis 626 yy ELISA 632 yy Fluorescence in situ hybridization 366 yy Gene editing 468 yy Gene therapy 474 yy Guthrie test 215 yy Hemoglobin electrophoresis 38 yy Immunofixation 554 yy Ion exchange chromatography 629 yy Ion selective electrodes 600 yy iPSC 473 yy Isoelectric focusing 628 yy Karyotyping 365 yy Lipofection 475 yy Mass spectrometry 634, 635 yy Next-generation sequencing 468 yy Northern blotting 462 yy Nuclear magnetic resonance 634 yy PET scan 129 yy Plasma protein electrophoresis 550 yy Polymerase chain reaction 400 yy Real-time PCR 404 yy Restriction digestion 459 yy Restriction fragment length Polymorphism 465 yy Salt fractionation 550 yy SDS-PAGE 627 yy Size-exclusion chromatography 629 yy Somatic cell nuclear transfer 473 yy Southern blotting 462 yy Transfection 475 yy Two-dimensional electrophoresis 628 yy Urine analysis 659 yy Urine dipstick test for glucose 645 yy Van den Bergh’s test 227 yy Various organ function tests Chap. 45 yy X-ray crystallography 633, 634 yy Yeast-hybrid systems 469
- 12. xxxii KeyContents DID YOU KNOW? In this book, I have explained many important and interesting concepts. Here is a selected list of few. yy P:O Ratio 83 yy Passenger mutations 426 yy Phosphorolysis 144 yy Photodynamic therapy 225 yy Phototherapy 229 yy Polymerase switch 390 yy Procollagen suicide 479 yy Pseudogene 116 yy Rapoport–Luebering shunt 32 yy Regan isoenzyme 642 yy Resistant starch 504 yy Riboswitches 451 yy Skewed lyonization 481 yy Stool osmotic gap 581 yy Suicide enzyme 302 yy Supramolecular assembly 23 yy Thermodynamic coupling 45 yy Translational recoding 437 yy Tumor microenvironment 494 yy Ubiquitin-proteasomal system 183 yy Ultratrace elements 499 yy Unfolded protein response 439 yy Uniparental disomy 482 yy Untranslated regions 418 yy Urea cyle 180 yy Warburg effect 128 yy Abzymes 52 yy Advanced glycation end products 172 yy Aptamers 362 yy Basis of hair-straightening 22 yy Beneficial mutations 426 yy Bifunctional enzyme 54 yy Biological homochirality 3 yy Cahill cycle 137 yy Cancer stem cells 494 yy Cancer vaccines 494 yy Carbohydrate-deficient transferrin 311 yy Catalytically perfect enzymes 123 yy Chemical chaperones 439 yy Circular RNAs 455 yy Circularization of mRNA during translation 417 yy Citrullinated proteins 11 yy CpG dinucleotides 455 yy De ritis ratio 642 yy Double Bohr Effect 34 yy Driver mutations 426 yy End replication problem 390 yy Enzyme class 7 (EC 7) 53 yy Epigenetics 455 yy Epistasis 482 yy Epithelial to mesenchymal transition 494 yy Epitranscriptomics 456 yy Fetal fibronectin 621 yy Flux-generating enzyme 100 yy FODMAPs 112 yy Gain of function mutations 425 yy Gene annotation 374 yy Genomic imprinting 482 yy Glycemic load 503 yy Glyceroneogenesis 297 yy Glypiation 604 yy Histone code 369 yy Hoogsteen base pairing 361 yy Hyperchromicity of denaturation 356 yy Ileal brake phenomenon 341 yy Immobilised enzymes 645 yy Isopeptide bond 17 yy Ketogenic diet 94 yy Lectins 608 yy Leloir pathway 162 yy Lipid raft 565 yy Lipoprotein (a) 290 yy Metabolic water 598 yy Non-mendelian inheritance 481 yy Oxygen debt 125 REFERENCES 1. Medical Council of India, Regulations on Graduate Medical Education, 1997 (Amended up to May, 2018), 2018, pg 38. 2. Medical Council of India, Regulations on Graduate Medical Education, 1997 (Amended up to May, 2018), 2018, pg 36.
- 13. I S E C T I O N Fundamental Concepts of Biochemistry Section Outline 1. Chemistry of Amino Acids 2. Protein Structure 3. Hemoglobin and Myoglobin 4. Bioenergetics 5. Enzymology 6. Biological Oxidation and Electron Transport Chain 7. Tricarboxylic Acid (TCA) Cycle
- 14. 1C H A P T E R Chemistry of Amino Acids Chapter Outline ‰‰ Standard Amino Acids ‰‰ 21st and 22nd Amino Acids ‰‰ Biological Homochirality ‰‰ Structure of Amino Acids and its Functional Relevance ‰‰ Ultraviolet (UV) Absorbance by Aromatic Amino Acids ‰‰ Buffering Action of Histidine ‰‰ Classification of Amino Acids ‰‰ Derived Amino Acids ¬¬ Non-protein Amino Acids ¬¬ Non-alpha Amino Acids ¬¬ Post-translational Modifications ‰‰ Isoelectric pH of Amino Acids ‰‰ Three-letter and One-letter Code of Amino Acids Amino acids are the monomeric units of proteins. In addition, they give rise to important molecules like heme, purine and pyrimidine nucleotides, polyamines, nitric oxide and creatine. STANDARD AMINO ACIDS Standard amino acids have their own codon(s) and they are found in proteins. Although 300 amino acids are found in nature, only 21 are coded by codons. The 21st amino acid selenocysteine utilizes a stop codon. ALL THE AMINO ACIDS IN HUMAN PROTEINS ARE L-AMINO ACIDS An asymmetric/chiral carbon is a carbon atom that is attached to 4 different types of atoms or groups of atoms. Except for glycine, all amino acids possess chiral centers and they can exist as either L or D enantiomer. All the amino acids in human proteins are in L-form (biological homochirality). Free D-amino acids (D-serine, D-glutamate) are found in brain as neurotransmitters. (Compare: All the monosaccharides in human body are in D-form, except L-fucose). Just have a look at the chapter outline before exams and try to recall what you have learnt. Go through the topic again if you want.
- 15. 5 ‰‰‰‰ Sulfur of cysteine has the property of binding to heavy metals—like arsenic and lead. This is why arsenite poisoning inactivates SH group containing enzymes and SH group containing British Anti-Lewisite (dimercaprol) is an antidote for heavy metal poisoning. Clinical Correlation What is the point of studying biochemistry unless we apply it in the clinical practice? So, I have given clinical correlation boxes. Let me show you some salient features of this book.
- 16. Bond, Disulphide Bond Cystinuria (Chapter 11.6) (Refer to page no. 216) is an inherited condition with excessive urinary excretion of cysteine and few other amino acids. In the acidic pH of urine, cysteine is converted into insoluble cystine which forms stone in the urinary tract. Alkalinization of urine is done to prevent the conversion of cysteine to cystine. Clinical Correlation Similar sounding terms: ‰‰ Cysteine - Amino acid ‰‰ Cystine - Dipeptide ‰‰ Cytosine - Pyrimidine base ‰‰ Cytidine - Nucleoside
- 17. Chapter1 ChemistryofAminoAcids ‰‰‰‰‰ Aromatic Amino Acids Absorb UV Light at 280 nm Compounds with conjugated double bonds absorb UV light that is why aromatic amino acids, porphyrins, purine and pyrimidine bases absorb UV light. Among the aromatic amino acids, tryptophan absorbs the maximum. Light-absorbing capacity of aromatic amino acids is used to estimate the protein concentration with spectrophotometer (instrument that can measure the light absorbance from infrared to ultraviolet range). With the absorbance value of a known concentration of protein solutions, a standard curve is made. Concentration of the protein is calculated using the standard curve. Compound λmax (nm) (Wavelength at which maximal light absorption occurs) Peptide bond 190–230 Purine and pyrimidine bases 260 Aromatic amino acids 280 NADH and NADPH 340 Porphyrin (Soret Band) 400 ‰‰‰ Giving information in a tabular format helps in quick registry, revision and recall. This book contains more than 250 tables!
- 18. 8 ‰‰ Histidine contributes to the buffering capacity of proteins. €€ The pKa of histidine is 6.0, so histidine is best at buffering at pH 6.0. The acidic amino acids have lower pKa values if compared to histidine, and the other basic amino acids have greater pKa values. Hence, the pKa of histidine, amongst all amino acids is the closest to the physiological pH of 7.4. ‰‰ Histidine binds to nickel. This property is used in affinity chromatography to separate histidine tagged proteins (This will be explained in Chapter 43) (Refer to page no. 630). High Yield His Basics are Loose - Histidine, Lysine and Arginine are basic amino acids Mnemonic High-Yield information is given in these kind of boxes. Who doesn't like a good mnemonic? You can always create your own mnemonic. If you have an interesting mnemonic, share with me.
- 19. 10 Classification Based on the Polarity of the Side Chain CONCEPT CORNER Which amino acids are polar? � All amino acids carrying a charged R group (positive/negative). � All amino acids with SH, OH or amide R group which enable them to make hydrogen bond with water. Try to make flow charts like this in exam instead of writing lengthy sentences. Concept corners in the book will help you understand the fundamentals.
- 20. 11 Chapter1 ChemistryofAminoAcids‰ ‰‰ Gamma Carboxyglutamic Acid (Gla) is a Result of Post-translational Modification Gamma carboxyglutamic acid (GLA) contains one more carboxyl group at the γ carbon which enables the dicarboxylate group to bind divalent calcium. γ-carboxylation is aided by vitamin K. GLA containing proteins are: ‰‰ Factor II, VII, IX, X ‰‰ Protein C, S, Z ‰‰ Osteocalcin, matrix GLA protein ‰‰ Nephrocalcin, transthyretin, periostin High Yield CONCEPT CORNER Although many textbooks consider citrulline as a nonprotein amino acid, it is actually found in proteins normally. Post-translational deimination of arginine produces citrulline in proteins. In certain autoimmune diseases, antibodies against these citrullinated proteins are found. For example, anticitrullinated peptide antibodies are more specific in the diagnosis of rheumatoid arthritis.
- 21. 13 Chapter1 ChemistryofAminoAcids Amino acid Three-letter code One-letter code Cysteine Cys C Glutamic acid Glu E Glutamine Gln Q Glycine Gly G Histidine His H Isoleucine Ile I Leucine Leu L Lysine Lys K Methionine Met M Phenylalanine Phe F Proline Pro P Serine Ser S Threonine Thr T Tryptophan Trp W Tyrosine Tyr Y Valine Val V Most common mutation in cystic fibrosis is ΔF508 which indicates the deletion of phenylalanine (F) at the 508th position of the CFTR protein. This is why you need to be familiar with one-letter code of amino acids. Clinical Correlation
- 22. 14 SectionI FundamentalConceptsofBiochemistry Short Answer Questions 1. Using your knowledge of one-letter code of amino acids, what can you infer from the following terms in relation to mutations found in proteins? a. ΔF508 b. K-RasG12D 2. What is cystine? What is its biomedical importance? 3. Why are amino acids called ‘amphoteric molecules’? Why do some amino acids like histidine have better buffering capacity at body pH, compared to glycine? 4. What are non-protein amino acids? Name any two. 5. Name the 21st amino acid. Which is the codon for this? Name any two enzymes containing the 21st aminoacid. 6. Classify the amino-acids based on the polarity and the charge on their R-group (side chain). 7. Define isoelectric pH (pI). What will be the charge on the amino acid if the surrounding pH is above, below and same as that of the pI of the amino acid? 8. What is g-carboxy glutamic acid (Gla)? Which vitamin is required for the formation of Gla? Name three Gla containing proteins. 9. Give three examples of amino acids with a non- alpha amino group, that have important functions in mammalian metabolism. SELF-ASSESSMENT 10. Give two examples each of acidic, basic and aromatic amino acids respectively. Multiple Choice Questions 1. Which one of the following amino acids is most likely to be found in the transmembrane region of a protein? a. Lysine b. Arginine c. Leucine d. Aspartate 2. When the following amino acids are separated by running them on agarose gel at pH 7, which one of them will migrate slowest towards the anode? a. Glycine b. Valine c. Aspartic acid d. Lysine 3. Which of the following amino acids contain polar but uncharged side-chain? a. Cysteine b. Leucine c. Methionine d. Glutamate 4. Which of the following amino acids can be phosphorylated? a. Cysteine b. Leucine c. Methionine d. Serine 5. Which of the following clotting factor does not contain gamma carboxyglutamate? a. Factor II b. Factor IV c. Factor IX d. Factor X 6. Which one of following amino acids is polar? a. Isoleucine b. Methionine c. Glutamic acid d. Tryptophan Key Points ‰‰ All the amino acids in human proteins are L-amino acids. D-amino acids are not found in proteins. ‰‰ D-amino acids are found in bacterial cell wall; vancomycin binds to D-alanyl-D-alanine sequence. ‰‰ Glycine is optically inactive. ‰‰ Selenocysteine is the 21st amino acid coded by UGA. ‰‰ Pyrrolysine is the 22nd amino acid coded by UAG; not found in humans. ‰‰ Among the polar amino acids, glycine is the least polar and arginine is the most polar. ‰‰ Methionine contains sulfur; does not contain–SH group. ‰‰ Reducing property of glutathione is due to the–SH (sulfhydryl/thiol/thioalcohol/mercaptan) group of cysteine.
- 23. 15 Chapter1 ChemistryofAminoAcids 7. Which one of the following amino acids is nonpolar? a. Glutamate b. Glutamine c. Histidine d. Methionine 8. Amino acid with aliphatic side chain is: a. Serine b. Leucine c. Threonine d. Aspartate 9. Nonprotein amino acid is: a. Aspartate b. Histidine c. Ornithine d. Tyrosine 10. Which of the following amino acid contains two chiral carbons? a. Leucine b. Valine c. Threonine d. Methionine 11. Cystine is formed by: a. Hydroxylation of cysteine molecule b. Carboxylation of cysteine molecule c. Peptide bond between two cysteine molecules d. Disulfide bond between cysteine molecule 12. Free SH group is present in: a. Cysteine b. Methionine c. Taurine d. Homoserine 13. Substitution of which one of the following amino acids in place of alanine would increase the absorbance of protein at 280 nm? a. Leucine b. Arginine c. Tryptophan d. Proline ANSWERS 1. c. 2. d. 3. a. 4. d. 5. b. 6. c. 7. d. 8. b. 9. c. 10. c. 11. d. 12. a. 13. c. Direct One-liner Type Questions 1. Optically inactive amino acid is ______ 2. Amino acids with indole group is called ______ 3. Amino acids with guanidino group is called ____ 4. Amino acids with imidazole group is known as _ 5. Most basic amino acid is ______ 6. Aromatic amino acids absorb UV light at the wave length of ___ nm 7. Amino acid from which selenocysteine is derived: ______ 8. 22nd amino acid is ______ 9. Amino acid involved in N-glycosylation is _____ 10. Amino acid acting as neurotransmitter is called ______ 11. Imino acid is ______ 12. One-letter code for phenylalanine is ______ 13. The codon for selenocysteine is ____ 14. Activated methionine is ____ ANSWERS 1. Glycine 2. Tryptophan 3. Arginine 4. Histidine 5. Arginine 6. 280 7. Serine 8. Pyrrolysine 9. Asparagine 10. Glycine, D-serine, D-Glutamate 11. Proline 12. F 13. UGA 14. S-Adenosyl methionine
- 24. Here is one whole sample chapter for you !
- 25. 14C H A P T E R Metabolism of Alcohol Chapter Outline ‰‰ Absorption of Alcohol ‰‰ Three Systems of Alcohol Metabolism ‰‰ Zero-order Kinetics ‰‰ Increased NADH/NAD Ratio in Alcoholism ‰‰ Reasons for Thiamine Deficiency ‰‰ Fetal Alcohol Syndrome ‰‰ Methanol Poisoning ‰‰ Carbohydrate-Deficient Transferrin ‰‰ Drugs Inhibiting Alcohol Metabolism ABSORPTION OF ALCOHOL Ethanol (C2 H5 OH) is completely miscible with water because it can make hydrogen bonds with water molecules. Major site of alcohol absorption is the upper small intestine. ‰‰ Stomach—20% absorption ‰‰ Small intestine—80% absorption ‰‰ Mouth—readily absorbed Rate of absorption is increased when alcohol is taken on empty stomach. Food intake reduces the rate of absorption by delaying the gastric emptying. Alcohol can freely diffuse across the cells. Metabolism of alcohol and its effect are influenced by gender, body weight, and genotype. METABOLISM OF ALCOHOL Alcohol is metabolized in liver by three different systems: 1. Cytosolic alcohol dehydrogenase—major pathway 2. Microsomal ethanol oxidizing system (MEOS)—induced by chronic alcohol ingestion 3. Peroxisomal catalase (minor pathway) Cytosolic Alcohol Dehydrogenase Pathway ‰‰ Alcohol dehydrogenase is the enzyme with EC number 1.1.1.1 ‰‰ This is a NAD+ dependent dehydrogenase. ‰‰ NAD+ binding domain of this and some other dehydrogenases is known as Rossmann fold. ‰‰ Converts ethanol to acetaldehyde and produces NADH + H+ . Sam ple C opy
- 26. 309 Chapter14 MetabolismofAlcohol Excess Alcohol Induces Microsomal Ethanol Oxidizing System ‰‰ Microsomal ethanol oxidizing system (MEOS) is an alternate pathway of ethanol metabolism. ‰‰ MEOS activity increases after chronic alcohol consumption. ‰‰ CYP2E1 is the predominant enzyme that converts ethanol to acetaldehyde. Zero-Order Kinetics Kinetics of alcohol elimination is said to be a zero-order process. This means that rate of removal of alcohol from the body is constant irrespective of the amount of alcohol. This is because of the saturation of the alcohol dehydrogenase with even low concentrations of alcohol. Sam ple C opy
- 27. 310 SectionII IntermediaryMetabolism Methanol and ethylene glycol are also metabolized by the same system that metabolizes the ethanol. Ingestion of illicit liquor and methylated sprit leads to methanol poisoning. Formaldehyde produced by methanol is more toxic than acetaldehyde. It causes toxic amblyopia and blindness. Ethylene glycol is a component of antifreeze. Both methanol and ethylene glycol poisoning cause raised anion gap metabolic acidosis. Increased NADH/NAD Ratio is the Biochemical Basis of Metabolic Derangements in Alcoholism Hypoglycemia ↑ NADH promotes the conversion of pyruvate to lactate and oxaloacetate to malate. Thus, it depletes the glucogenic substrates. Lactic acidosis ↑ NADH causes the conversion of pyruvate to lactate Gout ‰‰ Overproduction: Alcohol increases urate synthesis by enhancing the turnover of adenine nucleotides ‰‰ Under excretion: Lactic acid competes with uric acid for excretion in the urinary tubules Fatty liver ↑ NADH inhibits the isocitrate dehydrogenase. Citrate comes out of mitochondria and fatty acid synthesis is promoted. Liver damage Acetaldehyde forms adduct with proteins and toxic to hepatocytes 1 gram of alcohol provides 7 kcal. However, these calories are known as empty calories since they are not associated with nutrients like vitamins and minerals. Reasons for Thiamine Deficiency in Alcoholism ‰‰ Alcoholics do not take food properly. Therefore, the chance of dietary thiamine deficiency is more common. ‰‰ Moreover, alcohol inhibits thiamine absorption. Biochemical Basis of Fetal Alcohol Syndrome: Disruption of Retinoic Acid Signaling ‰‰ Retinol, a form of vitamin A is an alcohol. ‰‰ Alcohol dehydrogenase is also involved in the conversion of retinol to retinoic acid, an important molecule needed for growth and development. FAS-Fetal Alchol syndrome Sam ple C opy
- 28. 311 Chapter14 MetabolismofAlcohol Alcohol is a 7-letter word. Calorific value of alcohol is 7kcal/gram. Mnemonic ‰‰ Excess ethanol competes with the retinol for the conversion by alcohol dehydrogenase and thus affects the retinoic acid synthesis and thus disrupts the retinoic acid signaling pathway. Methanol Poisoning is Treated by Administration of Ethanol Ethanol competes with methanol and ethylene glycol for the active site of the alcohol dehydrogenase enzyme. This is the biochemical basis of use of ethanol in these poisoning conditions. Carbohydrate-Deficient Transferrin is a Marker of Chronic Alcoholism ‰‰ Transferrin is a glycoprotein. ‰‰ Alcohol inhibits the glycosylation of several glycoproteins, including transferrin. ‰‰ Chronic alcoholism leads to transferrin deficient in four to five sialic acid residues. ‰‰ Consumption of 80 g of alcohol/day leads to an increase in the plasma carbohydrate-deficient transferrin (CDT) concentration. ‰‰ Other marker of alcoholic liver disease: γ-glutamyl transpeptidase. Drugs Inhibiting Alcohol Metabolism Drug Target Enzyme Use Disulfiram Aldehyde dehydrogenase Aversion therapy Fomepizole Alcohol dehydrogenase Ethylene glycol poisoning ‰‰ PA12.1 Enumerate and describe the pathogenesis of disorders caused by alcohol ‰‰ PH1.20 Describe the effects of acute and chronic ethanol intake ‰‰ PH1.21 Describe the symptoms and management of methanol and ethanol poisonings ompetency Sam ple C opy
- 29. 312 SectionII IntermediaryMetabolism Short Answer Questions 1. Explain the biochemical basis of hypoglycemia, lactic acidosis, fatty degeneration of liver seen in alcoholic patients. 2. Name two drugs acting on the metabolism of alcohol. Mention their enzyme targets. 3. What is the biochemical basis of the following? a. Use of Ethanol to treat methanol poisoning b. Fetal alcohol syndrome Multiple Choice Questions 1. A 3-year-old girl was brought into the emergency room. She was cold and clammy and breathing rapidly. She was confused and lethargic. Her mother indicated that she had accidentally ingested automobile antifreeze (ethylene glycol) while playing in the garage. Followinggastrointestinallavageandactivated charcoal administration, a nasogastric tube for ethanol was administered. How will ethanol help in relieving the symptoms? a. Conjugate with ethylene glycol to form a soluble compound b. Induce the alcohol dehydrogenase enzyme SELF-ASSESSMENT c. Competitively inhibit the metabolism of ethylene glycol d. Promote the excretion of metabolite of ethylene glycol 2. Enzyme system in which of the following organelles is induced on chronic ingestion of alcohol? a. Cytosol b. Mitochondria c. Microsome d. Lysosome 3. Which of the following drug inhibits the enzyme aldehyde dehydrogenase? a. Flumazenil b. Fomepizole c. Disulfiram d. Ethanol 4. The conventional treatment for methanol toxicity is to administer ethanol. Which of the following explains the basis of this treatment? a. Ethanol acts as a competitive inhibitor to methanol b. Ethanol acts as a non-competitive inhibitor to methanol c. Ethanol destroys the enzymatic activity of alcohol dehydrogenase d. Ethanol blocks the entry of methanol within the cells ANSWERS 1. c. 2. c. 3. c. 4. a. Key Points ‰‰ Major site of absorption of alcohol is the upper small intestine. ‰‰ Calorific value of alcohol is 7 kcal/g. ‰‰ Respiratory quotient of alcohol is 0.6. ‰‰ Chronic consumption of ethanol induces microsomal CYP2E1. ‰‰ Carbohydrate-deficient transferrin is a marker of chronic alcoholism. ‰‰ γ-glutamyl transferase is elevated in various liver diseases including alcoholic liver diseases. ‰‰ ModeratealcoholconsumptionincreasesthesynthesisofapoA-I;increasesthelevelofHDL;lowerstheincidence of coronary heart disease. ‰‰ Moderate alcohol use increases the risk of breast cancer, hypertension, and stroke in women. Sam ple C opy
- 30. _ __________________________________________________________________ _ __________________________________________________________________ _ __________________________________________________________________ _ __________________________________________________________________ _ __________________________________________________________________ _ __________________________________________________________________ _ __________________________________________________________________ _ __________________________________________________________________ _______________________________________________________________________________________________ _______________________________________________________________________________________________ _______________________________________________________________________________________________ _______________________________________________________________________________________________ _______________________________________________________________________________________________ _______________________________________________________________________________________________ _______________________________________________________________________________________________ _______________________________________________________________________________________________ _______________________________________________________________________________________________ _______________________________________________________________________________________________ _______________________________________________________________________________________________ _______________________________________________________________________________________________ _______________________________________________________________________________________________ _______________________________________________________________________________________________ _______________________________________________________________________________________________ _______________________________________________________________________________________________ _______________________________________________________________________________________________ _______________________________________________________________________________________________ _______________________________________________________________________________________________ _______________________________________________________________________________________________ _______________________________________________________________________________________________ _______________________________________________________________________________________________ _______________________________________________________________________________________________ _______________________________________________________________________________________________ Note Sam ple C opy
- 31. VI S E C T I O N Review Section Outline � Named Reactions, Cycles and Pathways, Molecules � Pioneers of Biochemistry � The Most Common Genetic Disorders � Regulatory/Rate Limiting Steps of Metabolic Pathways � The First in History � Biochemical Tests Sam ple C opy
- 32. Appendix (Review) NAMED REACTIONS, CYCLES AND PATHWAYS, MOLECULES NAMED REACTIONS Lohman reaction Creatine phosphate + ADP → ATP + Creatine Fenton reaction Fe2+ + H2 O2 Fe3+ + OH• + OH– Haber-Weiss reaction • O2 − + H2 O2 → • OH + OH− + O2 Maillard reaction Reaction between amino acids and reducing sugars – leads to advanced glycation end products NAMED CYCLES AND PATHWAYS Cahill cycle Glucose-Alanine cycle Cori’s cycle Reutilisation of lactate (produced by RBC and exercising muscle) by liver in gluconeogenesis Embden Meyerhof Pathway Glycolysis Krebs-Henseleit cycle Urea cycle Leloir Pathway Galactose breakdown Meister cycle Glutathione mediated absorption of neutral amino acids Rapaport-luebering shunt 2,3 BPG shunt NAMED MOLECULES Warburg yellow enzyme Riboflavin Edman’s reagent 1-fluoro-2,4-dinitrobenzene (FDNB) Sanger’s reagent Phenyl isothiocyanate (PITC) Leventhal’s paradox A thought experiment related to protein folding Klenow fragment E. coli DNA polymerase without 5′ → 3′ exonuclease activity Rossman fold NAD(P)H binding domain of certain dehydrogenases Cori’s ester Glucose 1-phosphate Sam ple C opy
- 33. 668 SectionVI Review Contd… PIONEERS OF BIOCHEMISTRY Pioneer Discovery Alec Jeffreys DNA fingerprinting Andrew fire and Craig Mello siRNA Arber, Smith and Nathans Restrictionenzymes Arthur Kornberg DNApolymerase Avery, Macleod and McCarty DNA is the information molecule/genetic material Barbara Mcclintock Transposons Blobel Signal sequence hypothesis Dorothy Hodgkin Protein crystallography Frederick Sanger Sequencing of 1° structure of bovine insulin and sequencing of nucleotides (He got Nobel prize twice!) Goldstein and Brown LDL receptor and its relation to familial hypercholesterolemia Griffith Transformation experiment Jacob and Monad Operon model James Lind Scurvy and citrus fruit trial in HMS Salisbury Kary B Mullis Polymerase Chain Reaction Kohler and Milstein Monoclonal antibodies by Hybridoma technique Linus Pauling and Robert Corey 2o structure of protein Lohmann Discovered ATP in biochemical reactions Nirenberg, Khorana and Holley Genetic Code Paul berg Recombinant DNA technology Robert W. Holley Sequencing of tRNA Rosalind Franklin X-ray crystallographer whose work helped in the determination of the structure of DNA Ruska Electronmicroscope S.N. Dei Cholera toxin discovery Shinya Yamanaka Induced pluripotent stem cells (iPSC) SusumuTonegawa Gene rearrangements in immunoglobulins Thomas Cech and Sidney Altman Ribozyme Tiselius Electrophoresis Tswett Chromatography Venkatraman Ramakrishnan Ribosome structure Yalow and Berson Radioimmunoassay(RIA) Yellapragada Subbarao Discovered that ATP is the energy currency of the cell Amino acid in plasma Glutamine Anterior pituitary hormone Growth hormone Biological forms in the world Polysaccharides Nucleoprotein Histone Sam ple C opy
- 34. 669 Appendix(Review) Amino acid in plasma Glutamine Cell type in the human body Erythrocyte (RBC) Type of collagen in basement membrane Type IV Type of collagen in the body Type I Type of collagen in the cartilage (except white fibrocartilage) Type II Type of collagen in the bone and white fibrocartilage Type I Constituent of body Water Glycoprotein in basement membrane Laminin Glycosaminoglycan Chondroitin sulphate Heteropolysaccharides in the body Glycosaminoglycan Immunoglobulin IgG Lipid in chylomicron Triacylglycerol Membrane proteins of RBC Glycophorin and Band 3 anionic transporter Osmotically active component of the plasma Sodium Peripheral membrane protein of RBC Spectrin Platelet receptors GPIIb-GPIIIa complex Prokaryotic DNA polymerase DNA polymerase I Protein in HDL Apo A-I (70% of weight) followed by Apo AII Protein in the human body Collagens Saturated fatty acid in circulation Palmitic acid Sigma factor in E. coli Sigma 70 Stop signal for transcription termination RNA hairpin Tocopherol in extrahepatic tissues α-tocopherol THE MOST COMMON GENETIC DISORDERS Gene disorder worldwide Thalassemia Enzyme deficiency (enzymopathy) G6PD (mostly asymptomatic) Qualitative Hemoglobinopathy Sickle cell anemia Mutation in cystic fibrosis ΔF508 (Deletion of phenylalanine at 508th position) Viable chromosomal disorder Down syndrome (21 trisomy) 2nd most common autosomal trisomy resulting in live birth Edward syndrome (18 trisomy) Mutation in galactosemia in Caucasian population Q188R (replacement of glutamine by arginine) Gene mutated in congenital adrenal hyperplasia CYP21A2 (21-α hydroxylase) Mutation leading to permanent neonatal diabetes KCNJ11 (ATP sensitive K+ channel) Inherited urea-cycle defect OTC deficiency SCID X-linked SCID Saturated fatty acids present in the cell Palmitic acid (C16) and stearic acid (C18) Type of plasma membrane receptor GPCR (G-Protein Coupled receptor) Contd… Sam ple C opy
- 35. 670 SectionVI Review Gene disorder worldwide Thalassemia Type of prosthetic groups, cofactors for enzymes Metal ions Covalent modification regulating enzyme activity Phosphorylation dephosphorylation. Fatty acid in natural fats Oleic acid Chronic liver disorder worldwide Non-alcoholic fatty liver disease (NAFLD) Cause of Conjugated Hyperbilirubinemia Obstruction in the Biliary Tree Primaryimmunodeficiency IgA deficiency Sterol in the membranes of animal cells Cholesterol Lysosomal storage disease Gaucher’sdisease Cause of proteinuria Loss of integrity of the glomerular basement membrane (glomerular proteinuria) Clotting factor deficiency Factor VIII Hereditary bleeding disorder ‰‰ Von Willebrand disease ‰‰ Bernard-Souliersyndrome Gene mutated in cancers P53 Coagulopathy/inherited thrombophilia Factor V Leiden 2° structure of proteins α-helix Sphingolipid found in mammals Sphingomyelin DNA binding motif Helix turn helix Insoluble fiber in diet Cellulose Form of the DNA double helix B-DNA Type of point mutation Transition Separationmethodusedinproteomic study Two-dimensionalgel electrophoresis Oncogene involved in the development of human cancers RAS Cause of preventable blindness in children Vit A deficiency ‰‰ Toxin producing dilated cardiomyopathy ‰‰ Environmental teratogen ‰‰ Cause of cirrhosis in the Western world Alcohol Mode of inheritance of congenital malformations Multifactorial inheritance Inborn error of fatty acid oxidation Medium-chain fatty acyl CoA dehydrogenase deficiency Genetic error of amino acid transport Cystinuria Porphyria Porphyria cutanea tarda Hepatic porphyria Acute intermittent porphyria Porphyria in children Erythropoietic protoporphyria Defective enzyme in homocystinuria Cystathionine β-synthase Acceptor in transaminase reactions α - ketoglutarate (2-oxoglutarate) Trinucleotide repeat CAG Levelofgeneregulationineukaryotes Transcription initiation Cause of non-ketotichyperglycinemia P protein mutation Cause of insulin resistance Obesity Contd… Sam ple C opy
- 36. 671 Appendix(Review) Gene disorder worldwide Thalassemia Inherited cause of intellectual disability Fragile X syndrome Inherited platelet dysfunction Glanzmann thrombasthenia Biochemical abnormality in congenital hypertrophic pyloric stenosis Hyponatremic hypokalemic metabolic alkalosis with paradoxical aciduria. Inherited nonspherocytic hemolytic anemia Pyruvate kinase deficiency Hereditary hemolytic anemia Hereditary spherocytosis (G6PD deficiency is usually asymptomatic) Type of chromosomal translocation Robertsonian Vitamin deficiency in the United States Folate (B9 ) Inborn error in bile acid synthesis 3β-hydroxy Δ5 C27-steroid oxidoreductase (HSD3B7) Amino acids found in beta turns Glycine and Proline Gene mutation in hemochromatosis HFE C282Y Feedback/homeostatic systems in the body Negative feedback Renal stones in children Cysteine Cause of cobalamin deficiency Perniciousanemia REGULATORY/RATE LIMITING STEPS OF METABOLIC PATHWAYS Pathway Enzyme catalysing the rate-limiting step Glycolysis PFK-1 Glycogen synthesis Glycogen synthase Glycogenolysis Glycogen Phosphorylase β-oxidation of fatty acids CPT-I Fatty acid synthesis Acetyl-CoA Carboxylase Ketone body synthesis HMG-CoA synthase Cholesterolsynthesis HMG-CoAreductase De novo Purine synthesis PRPP synthetase is rate limiting; PRPP-glutamyl amidotransferase catalyzes the committed step De novo Pyrimidine synthesis CPS II Heme synthesis ALA synthase I HMP shunt G6PD TCA cycle Isocitratedehydrogenase Urea cycle CPS I Bile acid synthesis 7-α-hydroxylase (CYP7A1) Polyamine synthesis Ornithine decarboxylase Catecholaminesynthesis Tyrosine hydroxylase Triacylglycerolsynthesis Diacylglycerol acyltransferase Testicularsteroidogenesis STAR protein mediated uptake of cholesterol Sam ple C opy
- 37. 672 SectionVI Review THE FIRST IN HISTORY Genome to be sequenced Bacteriophage φX174 Genome that belongs to a free-living organism to be sequenced H. influenzae Sequence of human chromosome released Ch. 22 Protein to be sequenced (by sanger) ‘Bovine’ Insulin Metabolic pathway discovered Glycolysis Metabolic cycle tobediscovered Urea Cycle Disease treated by gene therapy ADA deficient SCID Ribozyme discovered (by Cech) 26S rRNA Molecular machine recognised Ribosome BIOCHEMICAL TESTS Test Analyte detected Alcian blue spot test Urinaryglycosaminoglycans Barfoed’s test Monosaccharide BCG dye binding method Albumin Benedict’s test All reducing substances (Reducing sugar, Uric acid, Ascorbate etc.) Bial’s test Pentose sugars Biuret reaction Amino acids and proteins (Both Qualitative and quantitative) Ehrlich aldehyde test Urobilinogen Ferric chloride test Phenylketonuria, Tyrosinemia, Alkaptonuria, MSUD Fouchet’s test Bilirubin in urine (Qualitative test) Gerhardt’s test, Rothera’s test Acetoacetate (ketone body) Hay’s sulphur test Bile salts in urine Molisch test All carbohydrates Ninhydrin reaction Proteins with minimum of 2 peptide bonds (qualitative). Sakaguchi test Arginine Seliwanoff’s test Fructose Shake test (foam stability test) of amniotic fluid Fetal lung maturity assessment Sulkowitch test Urinary Calcium Vandenberg test Differentiates conjugated and unconjugated bilirubin in serum (Quantitative test) Sam ple C opy
- 39. I hope you liked the sample pages. The book is available in bookstores near you and also in online stores. If you have any queries, contact me via: karthidr@gmail.com