09/24/2017

BIOCHEMISTRYimportant-note-for-indian-medical-mci-screening-entrance-exam/

By Live Dr - Wed Feb 11, 2:34 am

BIOCHEMISTRY

Essential amino acids
Mnemonic

MATTVILPhLy

Methionine

Arginine

Threonine

Tryptophan

Valine

Isoleucine

Leucine

Phenylalanine

Lysine

Semiessential aminoacids
Histidine

Arginine

PROTEIN STRUCTURE

STRUCTURE BONDS DETECTION
Primary Peptide bonds Edman’s degeneration technique
Secondary Hydrogen X-ray diffraction, crystallography, and nuclear magnetic resonance.
Tertiary Disulfide ————–do———–
Quaternary

————–do————

structure of proteins

Primary structure Linear sequence of amino acids, consisting of peptide bonds
Secondary structure Special structure of proteins, by twisting of polypeptide chains, consisting of alpha helix and beta pleated sheets
Tertiary structure Three dimensional structure of functional proteins
Quaternary structure Spatial arrangement of subunits composed of polypeptide chains

QUOTE CORNER

Success is the good fortune that comes from aspiration, desperation, perspiration and inspiration.-Evan Esar

ELEVENTH HOUR BIOCHEMISTRY                                                                                                         29

PROTEIN FUNCTION
Alpha 1 antitrypsin Inhibitor of trypsin
Alpha 1 lipoprotein Transport of cholesterol and phospholipids
Alpha 2 microglobulin Antitrypsin and antiplasmin activity
Haptoglobin Binds with free hemoglobin
Ceruloplasmin Transports copper
Hemopexin 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

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 Transports exogenous triglycerides
VLDL Transports endogenous triglyceride
LDL Transports cholesterol to peripheral tissues
HDL 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.

ELEVENTH HOUR BIOCHEMISTRY                                                                                                         30

VITAMIN COENZYME FORM
Thiamine 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 vitamin Enzyme/ Substance marker
B1 RBC transketolase
B2 RBC glutathione peroxidase
B6 Urine xanthurenic acid
Folic acid Urine FIGLU
B12 Urine methylmalonic acid

Specific dynamic action

substance %
Protein 30
Fat 13
Carbohydrates 5

Respiratory quotient

substance R.Q.
Carbohydrates 1
Protein 0.8
Fat 0.7
Nucleoside Pentose + N-base
Nucleotide 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

ELEVENTH HOUR BIOCHEMISTRY                                                                                                         31

CELL ORGANELLES WITH THEIR ENZYME MARKERS

ORGANELLE ENZYME MARKER
Peroxisomes Catalase, Uric acid oxidase
Endoplasmic reticulum Glucose-6-phosphatase
Mitochondria Glutamate dehydrogenate
Lysosome Acid phosphatase
Plasma membrane 5′ nucleotidase , Adenylyl cyclase , Na-K ATPase
Inner mitochondrial membrane ATP synthase
Nucleus DNA
Ribosome RNA
Golgi apparatus Galactosyl transferase
Cytosol Lactate dehydrogenase
INHIBITION TYPE MECHANISM
Competitive inhibition Inhibitor competes with the substrate and binds to the active site of the enzyme but doesn’t undergo any catalysis
Non-competitive inhibition 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
Uncompetitive inhibition Inhibitor doesn’t bind with the enzyme, but only binds with the enzyme-substrate complex
Allosteric inhibition 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-Gierke’s Glucose -6- phosphatase
Pompe’s Acid maltase( Acid α glucosidase)
Mc Ardle’s Muscle glycogen phosphorylase
Tarui’s disease Muscle phosphorylase
Niemann-Pick’s Sphingomyelinase
Farber’s Ceramidase
Gaucher’s β-glucosidase
Krabbe’s β-galactosidase
Tay-Sach’s Hexosaminidase-A

TRIVIAL TRUTH

The chemical n-acetyl-cysteine found in raw eggs is proven to help hangovers

ELEVENTH HOUR BIOCHEMISTRY                                                                                                         32

DISEASES WITH THEIR ENZYME DEFICIENCIES CONTINUED..

DISEASE ENZYME DEFICIENCY
Phenylketonuria Phenylalanine hydroxylase
Alkaptonuria Homogentisate oxidase
Albinism Tyrosinase
Fabry’s α-galactosidase
Metachromatic leucodystrophy Arylsulphatase A
Gyrate atrophy of retina Ornithine d-transaminase
Lesch-Nyhan syndrome HGPRT
Sandhoff Hexosaminidase-β
Wolmann Acid lipase
MPS-1 / Hurler’s syndrome α-L-iduronidase
MPS-2 L-iduronosulphate
Xeroderma pigmentosum DNA exinuclease
Sudden infant death syndrome Medium chain acyl CoA dehydrogenase
Maroteaux Lamy syndrome Arylsulphatase β
Maple syrup urine Branched chain α-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 Gaucher’s 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

ELEVENTH HOUR BIOCHEMISTRY                                                                                                         33

Rate limiting steps

reactions rate limiting enzymes
Porphyrin synthesis ALA synthetase
Fatty acid synthesis Acetyl CoA carboxylase
Uric acid synthesis Xanthine oxidase
Denovo purine biosynthesis PRPP synthetase

Glycolysis

Location Cytosol
Substrate level phosphorylation Phosphoglycerate kinase

Pyruvate kinase

Inhibitors Fluoride-Enolase

Oxamate- Glyceraldehyde 3 phosphate dehydrogenase

Bromohydroxycaetone phosphate-Phosphate isomerase

Irreversible steps Hexokinase

Phosphofructokinase

Pyruvate kinase

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 Autosomal recessive inheritance
Deficiency Phenylalanine hydroxylase
Neurological signs, mental retardation As brain cell are deprived of essential amino acids
High phenylalanine concentration Results in competitive inhibition of tyrosine leading to-

Blonde hair

Blue eyes

Fair skin

Accessory metabolic pathway leads to Accumulation of phenylacetic acid and other metabolites leading to mousy odour

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.

ELEVENTH HOUR BIOCHEMISTRY                                                                                                         34

Phenylketonuria continued…

Diagnosis Provocative protein meal test

A plasma phenylalanine level > 20 mg/dl

A normal plasma tyrosine level

Screening tests Guthrie’s test ferric chloride solution-green Colour

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

*Hartnup’s disease-

Hereditary disorder of Tryptophan metabolism

Clinical symptoms include dermatitis, ataxia, and mental retardation.

Characterised by low plasma levels of Tryptophan and their elevated urinary excretion.

Hb S Substitution of glutamate by valine  in B chain in the 6th position
Hb C Substitution of glutamate by lysine in B chain in the 6th position
Hb D Substitution of glutamate by valine in B chain in the 12th position
Hb E Substitution of glutamate by lysine in  chain in the 26th position
Valine replaced at 67th position of the B chain of Hb A molecule Hemoglobin type(functionally similar)
Aspartate Hb Bristol
Glutamate Hb Milwaukee
Alanine Hb Sydney
LDH1 Heart and RBC
LDH2 Heart and RBC
LDH3 Brain and kidney
LDH4 Liver and skeletal muscle
LDH5 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

ELEVENTH HOUR BIOCHEMISTRY                                                                                                         35

characteristics hemolytic jaundice obstructive jaundice hepatic jaundice
Serum bilirubin Unconjugated bilirubin increased Conjugate bilirubin is increased both are increased
Urine bilirubin Absent ++ +
Urobilinogen in urine + Absent absent
Stercobilinogen ++ absent decreased
Feces colour Black very pale pale
Urine colour No change very dark 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.

ELEVENTH HOUR BIOCHEMISTRY                                                                                                         36

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