BIOCHEMISTRY

ESSENTIAL AMINO ACIDS Mnemonic MATTVILPhLy Methionine Arginine Threonine Tryptophan Valine Isoleucine Leucine Phenylalanine Lysine SEMIESSENTIAL AMINOACIDS Histidine Arginine PROTEIN STRUCTURE STRUCTURE BONDS Primary Peptide bonds Secondary Hydrogen Tertiary Quaternary Disulfide DETECTION Edmans degeneration technique X-ray diffraction, crystallography, and nuclear magnetic resonance. --------------do------------------------do------------

STRUCTURE OF PROTEINS Primary Linear sequence of amino acids, consisting of peptide bonds structure Secondary Special structure of proteins, by twisting of polypeptide chains, structure consisting of alpha helix and beta pleated sheets Tertiary Three dimensional structure of functional proteins structure Quaternary Spatial arrangement of subunits composed of polypeptide chains structure QUOTE CORNER Success is the good fortune that comes from aspiration, desperation, perspiration and inspiration.-Evan Esar

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PROTEIN Alpha 1 antitrypsin Alpha 1 lipoprotein Alpha 2 microglobulin Haptoglobin Ceruloplasmin Hemopexin

FUNCTION Inhibitor of trypsin Transport of cholesterol and phospholipids Antitrypsin and antiplasmin activity Binds with free hemoglobin Transports copper Transports heme

Ubiquitin Eukaryotic protein for degradation of intracellular proteins Chaperones Proteins which play a role in the assembly or proper folding of other Proteins without themselves being components of the latter Creatinine Methionine + Arginine + Glycine Glutathione Glutamine + Cystine + Glycine Central minister assistant general BENEDICTS TEST FOR DETECTING SUGAR IN URINE Just pale green Trace 0-100mg % Greenish precipitate + 100-500mg% Greenish yellow precipitate ++ 500-1000 mg % Yellowish orange precipitate +++ 1000-2000mg% Brick red precipitate ++++ >2000mg % *Polarimeter is used to measure optical activity APOLIPOPROTEINS LIPID APOLIPOPROTEINS Chylomicron A I, A II, B 48 VLDL B100, C I, C II, C III. E LDL B100 HDL AI, AII, CI, C II, C III, D, E. Chylomicron VLDL LDL HDL Transports exogenous triglycerides Transports endogenous triglyceride Transports cholesterol to peripheral tissues Transports cholesterol from peripheral tissues to liver for degradation.

*The triene-tetraene ratio in plasma lipids can be used to diagnose extent of essential fatty acid deficiency TRIVIAL TRUTH During the Alaskan Klondike gold rush, (1897-1898) potatoes were practically worth

their weight in gold. Potatoes were so valued for their vitamin C content that miners traded gold for potatoes.
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VITAMIN Thiamine

COENZYME FORM TPP TDP Riboflavin FAD FMN Niacin NAD NADP Pantothenic acid CoA Acyl carrier protein Pyridoxine Pyridoxal phosphate Folic acid Tetrahydrofolate ENZYME / SUBSTANCE MARKERS OF VITAMIN DEFECIENCIES DEFICIENT ENZYME/ SUBSTANCE MARKER VITAMIN B1 RBC transketolase B2 RBC glutathione peroxidase B6 Urine xanthurenic acid Folic acid Urine FIGLU B12 Urine methylmalonic acid SPECIFIC DYNAMIC ACTION specific dynamic action n. Abbr. SDA An increase in the production of heat caused by the ingestion of food, especially proteins. SUBSTANCE Protein Fat Carbohydrates % 30 13 5

RESPIRATORY QUOTIENT SUBSTANCE R.Q. Carbohydrates 1 Protein 0.8 Fat 0.7 Nucleoside Nucleotide Pentose + N-base Nucleoside + phosphate

Nucleic acid Polymerization of nucleotides *Shine-Dalgarno sequence A polypurine sequence in bacterial mRNA, 7 nucleotides in front of initiation codon AUG. it is involved in binding of mRNA to ribosome, and hence initiation of protein synthesis. QUOTE CORNER All misfortune is but a stepping stone to fortune. Henry David Thoreau
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CELL ORGANELLES WITH THEIR ENZYME MARKERS ORGANELLE Peroxisomes Endoplasmic reticulum Mitochondria Lysosome Plasma membrane Inner mitochondrial membrane Nucleus Ribosome Golgi apparatus Cytosol INHIBITION TYPE Competitive inhibition Non-competitive inhibition Uncompetitive inhibition Allosteric inhibition ENZYME MARKER Catalase, Uric acid oxidase Glucose-6-phosphatase Glutamate dehydrogenate Acid phosphatase 5 nucleotidase , Adenylyl cyclase , Na-K ATPase ATP synthase DNA RNA Galactosyl transferase Lactate dehydrogenase MECHANISM Inhibitor competes with the substrate and binds to the active site of the enzyme but doesnt undergo any catalysis The inhibitor has no structural resemblance with substrate and binds at a site other than the active site bon the enzyme surface and thus impairs enzyme function Inhibitor doesnt bind with the enzyme, but only binds with the enzyme-substrate complex The allosteric modulator binds to the allosteric site and regulates enzyme activity

DISEASES WITH THEIR ENZYME DEFICIENCIES. DISEASE ENZYME DEFICIENCY Criggler-Najjar UDP-glucuronyl transferase Von-Gierkes Glucose -6- phosphatase Pompes Acid maltase( Acid glucosidase)

Mc Ardles Taruis disease Niemann-Picks Farbers Gauchers Krabbes Tay-Sachs

Muscle glycogen phosphorylase Muscle phosphorylase Sphingomyelinase Ceramidase -glucosidase -galactosidase Hexosaminidase-A

TRIVIAL TRUTH The chemical n-acetyl-cysteine found in raw eggs is proven to help hangovers
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DISEASES WITH THEIR ENZYME DEFICIENCIES CONTINUED.. DISEASE ENZYME DEFICIENCY Phenylketonuria Phenylalanine hydroxylase Alkaptonuria Homogentisate oxidase Albinism Tyrosinase Fabrys -galactosidase Metachromatic leucodystrophy Arylsulphatase A Gyrate atrophy of retina Ornithine d-transaminase Lesch-Nyhan syndrome HGPRT Sandhoff Hexosaminidase- Wolmann Acid lipase MPS-1 / Hurlers syndrome -L-iduronidase MPS-2 L-iduronosulphate Xeroderma pigmentosum DNA exinuclease Sudden infant death syndrome Medium chain acyl CoA dehydrogenase Maroteaux Lamy syndrome Arylsulphatase Maple syrup urine Branched chain -ketoacid dehydrogenase Acute Intermittent Porphyria Uroporphyrinogen-1 synthase Congenital erythropoeitic porphyria Uroporphyrinogen-3 cosynthase Porphyria cutanea tarda Uroporphyrinogen decarboxylase Erythropoeitic porphyria Ferrochelatase Maple syrup urine disease Alpha ketoacid decarboxylase Hereditary fructose intolerance Aldolase b Fructosuria Fructokinase b Galctosemia Galactose-1-phosphate uridyl transferase Essential pentosuria Xylitol dehydrogenase Mucolipidosis type I / Sialidosis Sialidase / Neuraminidase Enzyme therapy Gauchers disease Cerezyme-recombinantly produced mannose-terminated acid beta glucosidase

Stem cell gene therapy

SCID

RATE LIMITING STEPS REACTIONS RATE LIMITING ENZYMES Bile acid synthesis 7 alpha hydroxylase Cholesterol synthesis HMG- coA synthetase Urea synthesis Carbamoyl phosphate synthase I Glycolysis Phosphofructokinase QUOTE CORNER Self confidence is the first requisite to great undertakings-Samuel Johnson
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RATE LIMITING STEPS REACTIONS Porphyrin synthesis Fatty acid synthesis Uric acid synthesis Denovo purine biosynthesis GLYCOLYSIS Location Substrate level phosphorylation Inhibitors

RATE LIMITING ENZYMES ALA synthetase Acetyl CoA carboxylase Xanthine oxidase PRPP synthetase Cytosol Phosphoglycerate kinase Pyruvate kinase Fluoride-Enolase Oxamate- Glyceraldehyde 3 phosphate dehydrogenase Bromohydroxycaetone phosphate-Phosphate isomerase Hexokinase Phosphofructokinase Pyruvate kinase

Irreversible steps

TCA Location Mitochondria Substrate level phosphorylation Succinate thiokinase Inhibitors Arsenite-Alpha ketoglutarate dehydrogenase Malonate- Succinate dehydrogenase Fluoroacetate / Fluorocitrate- Aconitase Energy 1 Acetyl CoA 12 ATP 1 mole of glucose gives 2 ATP anaerobically 38 ATP aerobically

PHENYLKETONURIA Deficiency Neurological signs, mental retardation High phenylalanine concentration

Autosomal recessive inheritance Phenylalanine hydroxylase As brain cell are deprived of essential amino acids Results in competitive inhibition of tyrosine leading toBlonde hair Blue eyes Fair skin Accumulation of phenylacetic acid and other metabolites leading to mousy odour

Accessory metabolic pathway leads to

TRIVIAL TRUTH The average cup of coffee contains more than 1000 different chemical components, none of which is tasted in isolation but only as part of the overall flavour.
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PHENYLKETONURIA CONTINUED Diagnosis Provocative protein meal test A plasma phenylalanine level > 20 mg/dl A normal plasma tyrosine level Screening Guthries test ferric chloride solution-green Colour tests 2,4 dinitrophenol hydrazine-yellow precipitate Treatment Low phenylalanine levels, however it should not be completely eliminated Tyrosine becomes essential, hence adequate intake should be ensured *Hartnups diseaseHereditary disorder of Tryptophan metabolism Clinical symptoms include dermatitis, ataxia, and mental retardation. pellagra like symptoms Characterised by low plasma levels of Tryptophan and their elevated urinary excretion. Hb S Hb C Hb D Hb E Substitution of glutamate by valine in B chain in the 6th position Substitution of glutamate by lysine in B chain in the 6th position Substitution of glutamate by valine in B chain in the 12th position Substitution of glutamate by lysine in chain in the 26th position Hemoglobin type(functionally similar) Hb Bristol Hb Milwaukee Hb Sydney

Valine replaced at 67th position of the B chain of Hb A molecule Aspartate Glutamate Alanine

LDH1 LDH2 LDH3 LDH4 LDH5

Heart and RBC Heart and RBC Brain and kidney Liver and skeletal muscle Skeletal muscle and liver

CPK1- BB Brain CPK2- MB Heart CPK3- MM Muscle QUOTE CORNER It does not matter how slowly you go as long as you do not stop.- Confucius

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CHARACTERISTICS HEMOLYTIC JAUNDICE Serum bilirubin Unconjugated bilirubin increased Urine bilirubin Absent Urobilinogen in urine + Stercobilinogen ++ Feces colour Black Urine colour No change

OBSTRUCTIVE JAUNDICE Conjugate bilirubin is increased ++ Absent absent very pale very dark

HEPATIC JAUNDICE both are increased + absent decreased pale dark

UNCOUPLERS OF ELECTRON TRANSPORT CHAIN ARE 2,4 dinitrophenol Dinitrocresol Pentachlorophenol Triflurocarbonyl Aspirin Thyroxin Long chain free fatty acids Unconjugated bilirubin Muscle cells Can utilize glucose, fatty acids and ketone bodies Brain Can utilize ketone bodies and glucose Hepatocytes Cannot utilize ketone bodies *Liver cannot utilize ketone bodies

As it lack the enzyme necessary to convert acetoacetate to acetoacetyl co A

TRIVIAL TRUTH The prohibition of posthumously awarding Nobel prize fails to recognise achievements by a collaborator who happens to die before the prize is awarded. Rosalind Franklin, who was key in the discovery of the structure of DNA in 1953, died of ovarian cancer in 1958, four years before Francis Crick, James D. Watson and Maurice Wilkins were awarded the Prize for Medicine or Physiology in 1962.

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