The medical biochemistry - HIGH YIELD ( everything is...
Transcript of The medical biochemistry - HIGH YIELD ( everything is...
Dr.G.Bhanu Prakash - www.facebook.com/dr.g.bhanuprakash
The medical biochemistry - HIGH YIELD ( everything is covered )
PART - 1 Dr.G.Bhanu Prakash
CARBOHYDRATE CHEMISTRY:-
Formula:- Cn H2n On Glucose and mannose are epimers at C2 carbon Glucose galactose epimers at C4
Enantimomers are mirror images to each other. α and β cyclic forms of D-glucose known as anomers C1 is anomeric carbon
Benedict test reducing properties of sugars Sodium amalgam is used as reducing agent. Reduction of mono saccharides gives alcohols.
Aldose reductase converts aldehydes to alcohols. Fructose is converted to sorbitol dehydrogenase (liver) Monosaccharides gives needle shaped osazones.
Maltose gives sunflower shaped osazones Lactose gives powderpuff shaped osazones Maltose (α1-4) (glucose + glucose) – maltose (hydrolysed)
Lactose (βgalactose – βglucose) (β1-4) – lactase (hydrolysed) Sucrose (glucose-fructose) (α1- β2) Glucosidic bond- bond between monosaccharides.
Sucrose is hydrolysed by sucrase/invertase Dextrins are breakdown product of starch
Inulin is a polymer of fructose Glycogen and starch are polymer of glucose Inulin is need to assess GFR
Dietary fiber is cellulose (β-glycoside bond) D-glucoronic acid + N-acetyl glucosamine – Hyaluronic acid Keratin sulphate keeps cornea transparent
LIPID CHEMISTRY:-
Saturated fatty acids does not contain double bond Unsaturated fatty acids has double bonds Linolecic, linolenic and arachidonic acid (PUFA)
Deficiency of EFA – phyrnoderma (toad skin) Arachidonic acid gives Eicasonoids
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Unsaturated fatty acids exists in Cis form Hydrolysis of triacyl glycerin with alkali produces soaps (saponification)
Vit.E is naturally occuring antioxidant, superoxide dismutase, urase The medical biochemistry - FMGE Global institute of medical sciences www.gims-org.com
Purity of fatty acid is checked by iodine number RM number (Reichert-Meissl) – to check purity of butter
Phospholipids – free fatty acids + alcohol + phosphate + nitrogen Base Lecithin – choline ( nitrogen base) - ( lung surfactant)
Hormones like oxytocin and vasopressin action is mediated by phosphatidyl inositol Sphinogophospholipid :- cerebonic acid + sphingosine + phosphate + choline = sphingomyelin.
Phospholipases – A1, A2, C, D PLA2 (phospholipase A2)– give arachidonic acid Ganglioside GM2 accmulates in taysachs disease
Cholesterol –C27 H46 O Cholesterol has ohg group at C3. Double bond between C5-C6 Ergosterol is precussor for vit.D
Zaks test is used to identify the qualitative analysis of cholesterol Emulsified fats in the intestine forms Micelles PROTEINS AND AMINO ACID CHEMISTRY:-
kjeldahi’s method is used to find out protein in biological fluids. the amino acid glycine has H as side chain alanine has –CH3 (methyl) as side chain.
Cysteine and methionine are sulphur containing aminoacid. Aspartic acid and glutamic acid are acidic aminoacid Phenyl alanine, tyrosine, tryptophan –aromatic aminoacid
Alanine is glucogenic aminoacid. Leucine and lysine – ketogenic aminoacid.
Monosodium glutamate intolerance causes chinese restaurant syndrome D-penicilamine- used as chelating agent in Wilson’s disease (Accmulation of copper in brain)
N-acetyl cysteine used in cystic fibrosis and chronic renal failure. GABA-pentane is used as anticonvulsant Linear sequence of aminoacid seen in primary structure
α helix and β sheath – secondary structure.3 diminsional arrangement of protein –teritary 2 or more poly peptide chains- quartenary structure
Peptide bond – bond between 2 aminoacid. Sangers reagent – used to determine aminoacid sequence Sangers reagent used to determin insulin structure
Biurate is a compound formed by heating urea to 180 degrees . process is biurate reaction
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Copper sulphate is used for heatin in biurate reaction The medical biochemistry - FMGE
Global institute of medical sciences www.gims-org.com
Glutathione is involved in transport of amino acfid in intestine and kidney via glutanyl
cycle/meister cycle. Aspertame – artifical sweetner.
NUCLEIC ACIDS AND NUCLEOTIDES:-
Nucleotides – nitrogen base + pentose sugar + phosphate Nucleoside – nitrogen base + sugar Ribose and deoxyribose differs in C2
Purine nucleotide is Adenosin mono phosphate Pyramide nucleotide is Cyitidine MonoPhosphate, UradineMonoPhosphate Alopurinol used in the treatment of gout
5- fluorouracil used in the treatment of cancers Azathioprine is used to suppress immunological rejection during transplantation The width of double helix of DNA – 20 Å / 2 nm
Each turn of helix contains 10 base pairs Each turn of helix is 34 Å 2 strands of double helixd are hold by H-bonds DNA protiens are known as histones
B-DNA proposed by watson and crick in 1953 A-DNA has 11 base pairs per turn. A and B- DNA are right handed helix
Z-DNA is left handed helix Z-DNA has 12 base pairs per turn (zigzag) Formamide destahilses H-bonds, therefore it lowers Tm
Formamide used in recombinant DNA technology The sugar in RNA kis ribose
RNA is subjected to alkali hydrolysis and DNA cannot RNA can be identified lby orcinol colour reaction because of ribose Nucleolus synthesis r-RNA
DNA converts M-RNA converts protein M-RNA has 7 methyl guicnosine at 5 prime end The 3 prime kend contains poly- A tail (MRNA)
The stucture of t-RNA resembles clover leaf the acceptor arm of t-RNA has CCA cap (3prime) D-arm has dihyrouridine (t-RNA)
TψC arm has T, pseudouridine and C (tRNA) The medical biochemistry - FMGE
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ENZYMES :-
There are 6 cclasses of enzymes The functional unit of enzyme is holoenzyme
Holoenzyme is made up of apoenzyme (protein part) and co-enzyme (non-protein part). Increase in concentration of substrate increase enzyme velocity Km = ½ Vmax
Km = S (substrate concentration) Km-(michaelis-menten constant) Km is defined as the substrate concentration to produce ½ maximum velocity.
Low Km denotes strong affinity between enzyme and substrate When enzymes are exposed to C and above temperatures denaturation occurs. All enzymes are active at neutral PH (7)
The most common aminoacid at active site is serine INHIBITORS:-
Xanthine oxidase – allopurinol MAO (mono amino oxidase) – ephedrine, auphetamine
Dihydrofolate reducatse – aminopterin, amethopterin, methotrexate Acetylcholine esterase – succinyl choline Dihydropteroate synthase – sulfanilamide
Vit. Kepoxide reductase – dicumorol HMG co-A reducatse – lorastatin, compactin. Disulfiran is the drug used in the treatment of alcoholism
Transketolase requires TPP Streptokinase is used to remove blood clots Streptokinase converts plasminogen to plasmin
Asperginase is used in treatment of leukemias Increase amylase – acute pancreatitis
Increase SGPT (serum glutamate pyruvate transaminase) – liver diseases Increase alkaline phosphatase – rickets and bone diseases Increase acid phosphatase – prostate carcinoma
Increase aldolase – muscle dystrophy Increase troponin I – MI (first marker) Increase CPK1 – BB (brain)
Increase CPK2 – MB (heart) Increase CPK3 – MM (skeletal muscle)
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LIPID METABOLISM:-
TG – plasma concentration is 75-150 mg/dl Cholesterol – plasma concentration is 150-200 mg/dl
Hypercholesteremia - >250mg/dl Hormone sensitive TG lipase removes fatty acid from C1 or C3 of TAG glucagon, epinephrine, thyroxine, ACTH – increase cAMP – increase lipolysis.
Insulin – decrease cAMP – decrease lipolysis Glycerol is metabolized by liver.
FFA from Adipose Tissue are transported to liver by albumin. Brain, erythrocytes cannot utilize FA FA activation – cytosol (ATP, Co-A, mg2+) requires 2 ATP
Long chain FA are metabolized in peroxisomes Tangair’s disease – plasma HDL particles are almost absent Biosynthesis of FA in liver starts with glycerol and in adipose tissue with glucose and
acetyl Co-A Glycolipids act as receptors in cell membrane Absorption of cholesterol from intestine is by diffusion
Cholesterol gives bile salts, vit.D, steroid hormones (sex hormone and corticoids) Prostaglandin exhibit platelet aggregation, increase cAMP and vasodilation Obesity gene – leptin
β-oxidation – mitochondria activation of FA in β-oxidation – cytosol melanoyl Co-A inhibits – CAT-I, thus inhibits β-oxidation
CAT-I – outer mitochondrial membrane CAT-II – inner mitochondrial membrane Medium chain aceyl Co-A dehydrogenase, rate limiting step of β-oxidation.
β-oxidation of palmitate gives 106 ATP SIDS (sudden infant dead syndrome) – deficiency of medium chain aceyl Co-A
dehydrogenase (M-CAD.) Methyl melanoic academia – vit.B12 deficiency Methyl melanoic Co-A – requires Vit. B12
Zellweger syndrome – absence of peroxisomes cerebrohepatorenal syndrome. Zellweger syndrome – defect in long chain fatty breakdown α-oxidation – Refsums disease – accumulation of phytanic acid.
ω-oxidation requires – cytochrome P450 , NADPH, O2. Ketone bodies are synthesized in liver Ketone bodies are utilized by brain in prolonged starvation
HMG – CoA synthase – rate limiting step in ketone bodies synthesis Ketone bodies cannot be utilized by liver because of deficiency of thiophorase Acetone exhaled by lungs – sweetish odur.
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The medical biochemistry - FMGE Global institute of medical sciences www.gims-org.com
Detection of ketone bodies in urine – rothers test
Glucagon stimulates ketone bodies synthesis, insulin inhibits Treatment of keto acidosis – insulin Fatty acid bio-synthesis – cytosol.
Acetyl Co-A for fatty acid biosynthesis (FAB) obtains from citrate lyase NADPH in FAB obtained form HMP- pathway and malic enzyme
Acetyl Co-A carboxylase – rate limiting step in FAB Insulin stimulates FAB –glucagon inhibits Un-saturated fatty acids synthesized by fatty aceyl Co-A desaturase. Human lacks this
enzyme. TAG synthesis – adipose tissue Cerebronic acid + phyngosine = seramide
Seramide + phosphate + choline = sphingomyelin Phospholipase A1 – cleaves FFA at C1 Phospholipase A2 – cleavesFFA at C2
Phospholipase C - cleaves phosphate and glycerol found in lysozomes of hepatocytes L-CAT found in lungs L-CAT activity is associated with apo-A1 of HDL
Sphingomyelinase deficiency niemann’s pick’s desease Deficiency of seramidase Fauber’s disease Deficiency of β-galactidase krabbe’s disease
Deficiency of β-glucosidase gauchers disease Deficiency of α-galactidase fabrys disease Deficiency of hexosaminidase A – Taysachs disease
Cholesterol biosynthesis, liver- 50%, intestine- 15% Cholesterol synthesis- cytosol.
HMG- CoA reductase – rate limiting step in cholesterol biosynthesis Cholesterol formulae :- C27 H46 O Glucagon – glucocorticoids – decrease cholesterol biosynthesis
Compactin, lorastatin inhibits – HMG Co-A reductase HMG-CoA reductase also inhibited by bileacids 7-α-hydroxylase – rate limiting step in bileacid biosynthesis
95% of the bile is reabsorbed and return back to liver Primary bileacids – cholic acid chenodeoxycholic acid. Conjuation of bile acids done by – glycine , taurine
Deoxycholic acid,lithocholic acid – secondary bile acids Chenodiol treat for cholilithiasisctiatn of chylomi Chylomicrons has B48
VLDL has B100 HDL has apoprotein-A
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The medical biochemistry - FMGE
Global institute of medical sciences www.gims-org.com
Activation of chylomicrons and VLDL requires Apo-CII and Apo-E from HDL Lipoprotein lipase deficiency – hyperlipoprotenimia type I Defect in LDL receptors – type IIA
Excess apoB – type IIB Abnormality in apo-E – type III
Over production of TG – type IV Defect in HDL receptors – tangier’s disease
OXIDATIVE PHOSPHORYLATION AND ETC:- Phosphophenol pyruvate is 14.8 cal/mole.
S-adenosyl methionane is 10 cal/mole cAMP is 12 cal/mole ATP is 7.3 cal/mole
The inner mitochondrial membrane is impermeable to H+, K+ and Na+ Co-enzyme Q is also known as ubiquione Complex-I – NADH-co-encyme Q reductase inhibited by – amytal, rotenone,
pricydine-A Complex III – Co-enzyme Q-cytC reductase inhibited by antimycin A, BAL (british anti lewisite)
Comple IV – cytochrome oxidase inhibited by cyanide, CO, Na-azide. otation of -subunit is 12 ATP synthatase has F0 and F1 subunits.
F0 – channel protein C F1 – central γ subunit, 3α, 3β Mutation of mitochondrial DNA – oxiphos disease AKA (lebers hereditary optic
neuropathy) 2, A dinitrophenol – uncoupler of oxiphosphorylation Digomycin inhibits oxidative phosphorylation by binding to ATP synthetase 2 blockes
proton channels Atractyloside inhibits oxidative phosphorylation by blocking the adequate supply of ADP.
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VITAMINS:-
Vit.A:- Retinol is present in animals in the form of retinylester
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Retinal,retinol and retinoic acid are vitamers of vitamin A β- carotene gives l2 moles of retinal by 1 ’-1 ’ di-oxygenase
retinyl esters are transported by chylomicrons and stored in liver retinol is transported in circulation by RBP 9retinal binding protein) rods – dim light vision
cones – bright light vit-A required for rods rhodopsin present in rods
rhodopsin = 11-cis retinal + opsin during walds visual cycle rhodipsin is bleached to metarhodopsin-II which increases C-
GMP an degenerates nerve impulse Vit-A deficiency night blindness Serene deficiency of vit-A causes xerophthalmia, characterized of dryness of conjunctiva
and cornea, white triangular plaques, bitot’s spots are seen Xerophthalmia leads to keratomalacia causing total blindness Vit. D
Ergosterol (plants) ergocalciferol – vit. D2 Cholecalciferol (animals)- vit.D3 Vit-D synthesis takes place in skin.
1,25- Di-hydroxycholecalciferal is known as calcitriol i.e., active form of vit-D 25- α -hydroxylase and 1-α-hydroxylase requires cyt-p-450, NADPH and O2 Vit.D is essential for bone formation
Vit-D deficiency:- pickets – bowlegs – children; osteomalacia – Adults. Alkaline phosphatase activity elevated in rickets Vit-D is more toxic in over doses
Vit-D is transported in the circulation by α2-globulin 1-α-hydroxylase present in kidney and stimulated by PTH 25- α –hydroxylase present in liver
Vit-E:- Anti sterility vitamin
Also known as tocopherols α,β,γ,δ out of these α-tocopherols more active Vit-E is transported by VLDL and LDL in the circulation Normal plasma levels of tocopherols <1mg/dl
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Vit-E naturally occurring antioxidant and it requires selenium
Vit-E prevents peroxidation reactions of PUFA
ALA-synthase requires vit.E
Vit-K:-
Vit-K also synthesized by intestinal bacteria
Bile salts are essential for absorption of vit- K
Transported to liver by means of LDL
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Vit-K is responsible for post transitional modification of 2,7,9,10 clotting factors by
carboxylation of glutamic acid
Carboxylation of glutamic acid is inhibited by dicumarol
Deficiency of vit-K leads to lack of acive prothrobin in circulation
High doses of vit-K causes hemolytic anemia
Vit-C :-
Vit-C is required for collagen formation
Vit-C is co-enzyme for hydroxylation of proline and lysine, where protocollagen is
converted to collagen
Deficiency of vit-C leads to scurvy, delayed wound healing
Vit-B1 :-
co-enzyme – TPP
TPP required for PDH transketolase
Deficiency seen in the people who consume polished rice as a staple food
Elevation of pyruvate in plasma and excrets in urine
Wet-beriberi – edema – systolic increase – diastolic decrease – bouncing pulse.
Dry-beriberi – no edema – neurological manifestations are seen
Decrease transketoplase activity – Wernick’s korsakoff syndrome
Thyamine deficiency more commonly seen in alcoholics.