The Medical Biochemistry Part 1

8/19/2019 The Medical Biochemistry Part 1

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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 OnGlucose and mannose are epimers at C2 carbonGlucose galactose epimers at C4Enantimomers are mirror images to each other.α and β cyclic forms of D-glucose known as anomersC1 is anomeric carbonBenedict test reducing properties of sugarsSodium 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 osazonesLactose gives powderpuff shaped osazonesMaltose (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/invertaseDextrins are breakdown product of starchInulin is a polymer of fructoseGlycogen and starch are polymer of glucoseInulin is need to assess GFRDietary fiber is cellulose (β-glycoside bond)D-glucoronic acid + N-acetyl glucosamine – Hyaluronic acidKeratin sulphate keeps cornea transparent

LIPID CHEMISTRY:-

Saturated fatty acids does not contain double bondUnsaturated fatty acids has double bondsLinolecic, 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 formHydrolysis of triacyl glycerin with alkali produces soaps (saponification)

Vit.E is naturally occuring antioxidant, superoxide dismutase, uraseThe medical biochemistry - FMGEGlobal institute of medical sciences www.gims-org.com

Purity of fatty acid is checked by iodine numberRM number (Reichert-Meissl) – to check purity of butterPhospholipids – free fatty acids + alcohol + phosphate + nitrogen BaseLecithin – choline ( nitrogen base) - ( lung surfactant)Hormones like oxytocin and vasopressin action is mediated by phosphatidyl inositolSphinogophospholipid :- cerebonic acid + sphingosine + phosphate + choline =sphingomyelin.Phospholipases – A1, A2, C, DPLA2 (phospholipase A2) – give arachidonic acidGanglioside GM2 accmulates in taysachs diseaseCholesterol –C27 H46 OCholesterol has ohg group at C3. Double bond between C5-C6Ergosterol is precussor for vit.DZaks test is used to identify the qualitative analysis of cholesterolEmulsified fats in the intestine forms MicellesPROTEINS AND AMINO ACID CHEMISTRY:-kjeldahi’s method is used to find out protein in biological fluids. the amino acid glycine has H as side chainalanine has –CH3 (methyl) as side chain.Cysteine and methionine are sulphur containing aminoacid.

Aspartic acid and glutamic acid are acidic aminoacidPhenyl alanine, tyrosine, tryptophan –aromatic aminoacid Alanine is glucogenic aminoacid.Leucine and lysine – ketogenic aminoacid.Monosodium glutamate intolerance causes chinese restaurant syndromeD-penicilamine- used as chelating agent in Wilson’s disease (Accmulation of copper inbrain)N-acetyl cysteine used in cystic fibrosis and chronic renal failure.GABA-pentane is used as anticonvulsantLinear sequence of aminoacid seen in primary structureα helix and β sheath – secondary structure.3 diminsional arrangement of protein –teritary2 or more poly peptide chains- quartenary structurePeptide bond – bond between 2 aminoacid.Sangers reagent – used to determine aminoacid sequenceSangers reagent used to determin insulin structureBiurate is a compound formed by heating urea to 180 degrees . process is biuratereaction

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Copper sulphate is used for heatin in biurate reactionThe medical biochemistry - FMGEGlobal 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 + phosphateNucleoside – nitrogen base + sugarRibose and deoxyribose differs in C2Purine nucleotide is Adenosin mono phosphatePyramide nucleotide is Cyitidine MonoPhosphate, UradineMonoPhosphate

Alopurinol used in the treatment of gout5- fluorouracil used in the treatment of cancers

Azathioprine is used to suppress immunological rejection during transplantation Thewidth of double helix of DNA – 20 Å / 2 nmEach turn of helix contains 10 base pairs Each turn of helix is 34 Å2 strands of double helixd are hold by H-bondsDNA protiens are known as histonesB-DNA proposed by watson and crick in 1953

A-DNA has 11 base pairs per turn. A and B- DNA are right handed helixZ-DNA is left handed helix

Z-DNA has 12 base pairs per turn (zigzag)Formamide destahilses H-bonds, therefore it lowers TmFormamide used in recombinant DNA technologyThe sugar in RNA kis riboseRNA is subjected to alkali hydrolysis and DNA cannotRNA can be identified lby orcinol colour reaction because of riboseNucleolus synthesis r-RNADNA converts M-RNA converts proteinM-RNA has 7 methyl guicnosine at 5 prime endThe 3 prime kend contains poly- A tail (MRNA)The stucture of t-RNA resembles clover leafthe 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

Global institute of medical sciences www.gims-org.com

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ENZYMES :-

There are 6 cclasses of enzymesThe 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 velocityKm = ½ VmaxKm = 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 substrateWhen 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 – allopurinolMAO (mono amino oxidase) – ephedrine, auphetamineDihydrofolate reducatse – aminopterin, amethopterin, methotrexate

Acetylcholine esterase – succinyl cholineDihydropteroate synthase – sulfanilamide

Vit. Kepoxide reductase – dicumorolHMG co-A reducatse – lorastatin, compactin.Disulfiran is the drug used in the treatment of alcoholismTransketolase requires TPP

Streptokinase is used to remove blood clotsStreptokinase converts plasminogen to plasmin Asperginase is used in treatment of leukemiasIncrease amylase – acute pancreatitisIncrease SGPT (serum glutamate pyruvate transaminase) – liver diseasesIncrease alkaline phosphatase – rickets and bone diseasesIncrease acid phosphatase – prostate carcinomaIncrease aldolase – muscle dystrophyIncrease troponin I – MI (first marker)Increase CPK1 – BB (brain)Increase CPK2 – MB (heart)Increase CPK3 – MM (skeletal muscle)

The medical biochemistry - FMGEGlobal institute of medical sciences www.gims-org.com

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LIPID METABOLISM:-

TG – plasma concentration is 75-150 mg/dlCholesterol – plasma concentration is 150-200 mg/dl

Hypercholesteremia - >250mg/dlHormone sensitive TG lipase removes fatty acid from C1 or C3 of TAGglucagon, epinephrine, thyroxine, ACTH – increase cAMP – increase lipolysis.Insulin – decrease cAMP – decrease lipolysisGlycerol is metabolized by liver.FFA from Adipose Tissue are transported to liver by albumin.Brain, erythrocytes cannot utilize FAFA activation – cytosol (ATP, Co-A, mg2+) requires 2 ATPLong chain FA are metabolized in peroxisomesTangair’s disease – plasma HDL particles are almost absentBiosynthesis of FA in liver starts with glycerol and in adipose tissue with glucose andacetyl Co-AGlycolipids act as receptors in cell membrane

Absorption of cholesterol from intestine is by diffusionCholesterol gives bile salts, vit.D, steroid hormones (sex hormone and corticoids)Prostaglandin exhibit platelet aggregation, increase cAMP and vasodilationObesity gene – leptinβ-oxidation – mitochondriaactivation of FA in β-oxidation – cytosolmelanoyl Co-A inhibits – CAT-I, thus inhibits β-oxidationCAT-I – outer mitochondrial membrane

CAT-II – inner mitochondrial membraneMedium chain aceyl Co- A dehydrogenase, rate limiting step of β-oxidation.β-oxidation of palmitate gives 106 ATPSIDS (sudden infant dead syndrome) – deficiency of medium chain aceyl Co-Adehydrogenase (M-CAD.)Methyl melanoic academia – vit.B12 deficiencyMethyl melanoic Co-A – requires Vit. B12Zellweger syndrome – absence of peroxisomes cerebrohepatorenal syndrome.Zellweger syndrome – defect in long chain fatty breakdownα-oxidation – Refsums disease – accumulation of phytanic acid.ω-oxidation requires – cytochrome P450 , NADPH, O2.Ketone bodies are synthesized in liverKetone bodies are utilized by brain in prolonged starvationHMG – CoA synthase – rate limiting step in ketone bodies synthesisKetone bodies cannot be utilized by liver because of deficiency of thiophorase

Acetone exhaled by lungs – sweetish odur.


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Activation of chylomicrons and VLDL requires Apo-CII and Apo-E from HDLLipoprotein lipase deficiency – hyperlipoprotenimia type IDefect in LDL receptors – type IIAExcess apoB – type IIB

Abnormality in apo-E – type IIIOver production of TG – type IVDefect in HDL receptors – tangier’s disease

OXIDATIVE PHOSPHORYLATION AND ETC:-

Phosphophenol pyruvate is 14.8 cal/mole.S-adenosyl methionane is 10 cal/molecAMP is 12 cal/mole

ATP is 7.3 cal/moleThe inner mitochondrial membrane is impermeable to H+, K+ and Na+Co-enzyme Q is also known as ubiquioneComplex-I – NADH-co-encyme Q reductase inhibited by – amytal, rotenone,pricydine-AComplex 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 opticneuropathy)2, A dinitrophenol – uncoupler of oxiphosphorylationDigomycin inhibits oxidative phosphorylation by binding to ATP synthetase 2 blockesproton channels

Atractyloside inhibits oxidative phosphorylation by blocking the adequate supply of ADP.


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 Aβ- carotene gives l2 moles of retinal by 1 ’ -1 ’ di-oxygenaseretinyl esters are transported by chylomicrons and stored in liverretinol is transported in circulation by RBP 9retinal binding protein)rods – dim light vision

cones – bright lightvit-A required for rodsrhodopsin present in rodsrhodopsin = 11-cis retinal + opsinduring walds visual cycle rhodipsin is bleached to metarhodopsin-II which increases C-GMP an degenerates nerve impulse

Vit-A deficiency night blindnessSerene deficiency of vit-A causes xerophthalmia, characterized of dryness of conjunctivaand cornea, white triangular plaques, bitot’s spots are seen Xerophthalmia leads to keratomalacia causing total blindness

Vit. DErgosterol (plants) ergocalciferol – vit. D2Cholecalciferol (animals)- vit.D3

Vit-D synthesis takes place in skin.1,25- Di-hydroxycholecalciferal is known as calcitriol i.e., active form of vit-D25- 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 PTH25- 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 circulationNormal plasma levels of tocopherols


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Vit-K is responsible for post transitional modification of 2,7,9,10 clotting factors bycarboxylation of glutamic acidCarboxylation of glutamic acid is inhibited by dicumarolDeficiency 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 isconverted to collagenDeficiency of vit-C leads to scurvy, delayed wound healing

Vit-B1 :-co-enzyme – TPPTPP required for PDH transketolaseDeficiency seen in the people who consume polished rice as a staple foodElevation of pyruvate in plasma and excrets in urineWet-beriberi – edema – systolic increase – diastolic decrease – bouncing pulse.Dry-beriberi – no edema – neurological manifestations are seenDecrease transketoplase activity – Wernick’s korsakoff syndrome Thyamine deficiency more commonly seen in alcoholics.

The Medical Biochemistry Part 1

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