Biochemistry -- HIGH YIELD (everything is covered)
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. and 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 (1-4) (glucose + glucose) maltose (hydrolysed) Lactose (galactose glucose) (1-4) lactase (hydrolysed) Sucrose (glucose-fructose) (1- 2) 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 (-glycoside bond) D-glucoronic acid + N-acetyl glucosamine Hyaluronic acid Keratin sulphate keeps cornea transparent
LIPID CHEMISTRY:-
Biochemistry -- HIGH YIELD (everything is covered)
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 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 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:kjeldahis 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.
Biochemistry -- HIGH YIELD (everything is covered)
Monosodium glutamate intolerance causes chinese restaurant syndrome D-penicilamine- used as chelating agent in Wilsons 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 helix and 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 Copper sulphate is used for heatin in biurate reaction. Glutathione is involved in transport of amino acfid in intestine and kidney via glutanyl cycle/meister cycle. Aspertame artifical sweetner.
NUCLEIC ACIDS AND NUCLEOTIDES:-
Biochemistry -- HIGH YIELD (everything is covered)
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 / 2 nm Each turn of helix contains 10 base pairs Each turn of helix is 34 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) TC arm has T, pseudouridine and C (tRNA)
ENZYMES :There are 6 cclasses of enzymes
Biochemistry -- HIGH YIELD (everything is covered)
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 = Vmax Km = S (substrate concentration) Km-(michaelis-menten constant) Km is defined as the substrate concentration to produce 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)
Biochemistry -- HIGH YIELD (everything is covered)
Increase CPK3 MM (skeletal muscle)
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 Tangairs 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 -oxidation mitochondria activation of FA in -oxidation cytosol melanoyl Co-A inhibits CAT-I, thus inhibits -oxidation CAT-I outer mitochondrial membrane CAT-II inner mitochondrial membrane Medium chain aceyl Co-A dehydrogenase, rate limiting step of oxidation. -oxidation of palmitate gives 106 ATP SIDS (sudden infant dead syndrome) deficiency of medium chain
Biochemistry -- HIGH YIELD (everything is covered)
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 -oxidation Refsums disease accumulation of phytanic acid. -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. 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 niemanns picks desease Deficiency of seramidase Faubers disease Deficiency of -galactidase krabbes disease
Biochemistry -- HIGH YIELD (everything is covered)
Deficiency of -glucosidase gauchers disease Deficiency of -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--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
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 tangiers disease
Biochemistry -- HIGH YIELD (everything is covered)
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, Naazide. otation of -subunit is 12 ATP synthatase has F0 and F1 subunits. F0 channel protein C F1 central subunit, 3, 3 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.
Biochemistry -- HIGH YIELD (everything is covered)
VITAMINS:Vit.A:Retinol is present in animals in the form of retinylester Retinal,retinol and retinoic acid are vitamers of vitamin A - 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, bitots 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- -hydroxylase and 1--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
Biochemistry -- HIGH YIELD (everything is covered)
Vit-D is transported in the circulation by 2-globulin 1--hydroxylase present in kidney and stimulated by PTH 25- hydroxylase present in liver Vit-E:Anti sterility vitamin Also known as tocopherols ,,, out of these -tocopherols more active Vit-E is transported by VLDL and LDL in the circulation Normal plasma levels of tocopherols <1mg/dl 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 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
Biochemistry -- HIGH YIELD (everything is covered)
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 Wernicks korsakoff syndrome Thyamine deficiency more commonly seen in alcoholics. B2 RIBOFLAVIN:Coenzymes FMN, FAD Used in oxidation reduction reactions Deficiency cheilosis, glosittis, dermatitis Assessment of glutathione reductase in erythrocytes will be useful in accessing riboflavin deficiency NIACIN:Coenzyme NAD, NADP Pellagra preventive factor Niacin coenzymes synthesized from tryptophan Niacin deficiency results pellagra Pellagra symptoms diarrhea, dementia, dermatitis death HD Niacin inhibits lipolysis Niacin is used in treatment of hyperlipoprotenuria type_IIB. (increased VLDL, increased LDL)
Biochemistry -- HIGH YIELD (everything is covered)
PYRIDOXINE: - B6 Coenzyme pyridoxine, pyridoxal pyridoxamine Pyridoxine used in transamination, decarboxylation, deamination. Active form is pyridoxal phosphate (PLP) transamination It is required for the production of the monoamine neurotransmitters serotonin, dopamine, norepinephrine and epinephrine, as it is the precursor to pyridoxal phosphate: cofactor for the enzyme aromatic amino acid decarboxylase. This enzyme is responsible for converting the precursors 5hydroxytryptophan (5-HTP) into serotonin and levodopa (L-DOPA) into dopamine, noradrenaline and adrenaline. As such it has been implicated in the treatment of depression and anxiety. DEFICIENCY MANIFESTATIONS:1. neurological symptoms 2. excretion of xanthurenic acid in urine 3. drugs isoniazid and penicillamine can cause B6 deficiency. BIOTIN B7 It is required for carboxylation reactions Eg.:- 1. acetyl CoA carboxylase 2. propony CoA carboxylase 3. pyruvate carboxylase PANTOTHENIC ACID:also known as coenzyme A deficiency burning feet syndrome FOLIC ACID:it is important for one carbon metabolism the active form if tetrahydrofloate TH4 or THF the most common vitamin deficiency important for the synthesis of nitrogenous bases in DNA and RNA. Supplemented in pregnancy to prevent neural tube defects Deficiency of folic acid megaloblastic anemia. In folic acid deficiency FIGLU excreted in urine. (FIGLU- formiminoglutamate)
Biochemistry -- HIGH YIELD (everything is covered)
VITAMIN B12 (COBALAMIN) The absorption of vit-B12 requires intrinsic factor, intrinsic factor produced by gastric parietal cells Absorption of B12 into mucosal cells is Ca+2 dependent In mucosal cells B12 converts to methyl B12 From the mucosal cells transported in the plasma by transcobalamins i.e., Tc-I and Tc-II Methyl B12 (mucosal cells) 90% binds to Tc-I and 10% binds to Tc-II Vit-B12 stores in liver, as deoxyadenosyl B12 (storage form of vit B12) DEFICIENCY:Methyl melanoic acidemia Pernicious anemia Neurological manifestations (optic neuropathy) Use schilling test to detect deficiency Vit-B12 deficiency - most common cause is malabsorption sprue . HAEMOGLOBIN AND PORPHYRINS:METABOLISM:Heme contains porphyrin molecule known as protoporphyrin IX Heme contains 4 pyrole rings The central atom of heme contains Fe The adult hemoglobin 2,2 HbA1 Fetal hemoglobin 2 2 HbF HbA2 2 2 Glycosylated hemoglobin Hb A1 C 2 2 glucose (diabetes) Fetal Hb has more affinity towards O2 than adult HbF 100% ; HbA1 95%. In heme if Fe2+ oxidizes to form Fe3+ known methehemoglobin
Biochemistry -- HIGH YIELD (everything is covered)
BIOSYNTHESIS OF HEME:Heme synthesis take place in liver ALA synthase is rate limiting step in heme biosynthesis
HEME METABOLISM :Bilirubin bound to albumin to form bilirubin albumin complex
Enters liver for conjugation Bilirubin enters into intestine where it reacts with bacterial enzymes to form stercobilin which enters into feces 1 gm of Hb gives 35 mg of bilirubin Bilirubin- albumin complex binds to receptor LIGANDIN which in present on hepatocytes Porphyrias :CARBOHYDRATE METABOLISM:Insulin dependent glucose transport GLIT-4 skeletal muscle, adipose tissue GLUT-1 erythrocytes GLYCOLYSIS CYCLE:Location cytosol of all most all the cells Glucokinase liver, hexokinase other tissues Hexokinase low Km, glucokinase- High Km (PFK-1) Phosphofructokinase-1 rate limiting step Spilitting aldolase-A . 7 ATP in aerobic glycolysis and 2 ATP in anerobic Glycolysis in RBC is always anerobic IRREVERSIBLE STEPS:Hexokinase PFK-1 Pyruvate kinase ( deficiency hemolytic anemia )
Biochemistry -- HIGH YIELD (everything is covered)
INHIBITORS:Glycerol dehyde 3 phosphate dehydrogenase iodo acetate ,arsenate Enolase fluoride Phospphotriose isomerase - bromohydroxy acetone phosphate End product of aerobic glycolysis pyruvate End product of anaerobic glycolysis lactate Glycolysis in erythrocytes is always anaerobic Number of ATP under aerobic glycolysis 7 Number of ATP under anaerobic glycolysis 2 PFK-1 is regulated by PFK-2 A product of glycolysis 2,3 BPG combines with hemoglob9in and unloads O2 to tissues. Increase 2,3-BPG shifts O2 /Hb dissociation curve to right Decrease 2,3-BPG shifts O2/Hb dissociation curve to left. PDH COMPLEX: Location mitochondria Enzyme complexes:1. E1 pyruvate dehydrogenase TPP 2. E2 dihydro lipoyl transacetylase lipoamide ,CoA 3. E3 dihydro lipoyl dehydrogenase NAD, FAD Inhibitors arsenic poisoning TCA CYCLE:Location mitochondria Citrate synthase - rate limitin step NADH produce in :1. iso citrate dehydrogenase 2. -ketoglutarate dehydrogenase 3. malate dehydrogenase FADH produced by succinate dehydrogenase GTP produced by succinate thiokinase
Biochemistry -- HIGH YIELD (everything is covered)
INHIBITORS:1. Aconitase fluroacetate 2. -keto glutarate dehydrogenase arsenate 3. Succinate dehydrogenase malonate Number of ATP produced from 1 Acetyl Co-A is 10. GLUCONEOGENESIS:Synthesis of glucose from non-carbohydrate compounds. 160 gms of glucose required per day (whole body) 120 gms of glucose is required brain Location:- initial step mitochondria ; key step cytosol Rate limiting step pyruvate carboxylase Alanin glucogenic aminoacid Glucagon stimulates gluconeogenesis, insulin inhibits lpha- cells secrets glucagone Alcohol inhibits gluconeogenesis induces hypoglycemia GLYCOGEN METABOLISM Liver glycogen maintains blood glucose Muscle glycogen is used ony for muscle Glycogenesis in muscle starts with hexokinase Glycogenesis in liver starts with glucokinase Glycogen in protein produced by liver acts as initiator of glycogen synthesis The tyrosine residue of glycogenin adds glucose from UDP-G to form glycogen primer Glycogen synthatase rate limiting step in glycogen synthesis Glycogen phosphorylase breaks glycogen at 1-4 residues. Glucagons stimulates glycogen breakdown in liver Epinephrine stimulates glycogen breakdown in muscle Calcium promotes glycogen breakdown by Ca+2 colmodulin complex Glucose 6 phosphatase deficiency Von Gireks disease Lysosomal (1, 4) glucosidase deficiency Pompes disease
Biochemistry -- HIGH YIELD (everything is covered)
heart is more commonly involved death occurs due to heart failure. De-branching enzyme deficiency Andersons disease Muscle glycogen phosphorylase deficiency MC Ardles disease Liver glycogen phosphorylase Hers disease Phosphofructokinase Taruris disease erythocytes, hemolysis HMP PATHWAY:HMP pathway is only pathway which synthesizes NADPH in RBC (required for antioxidant reaction) Rate limiting step glucose 6 phosphate dehydrogenase Deficiency of glucose 6 phosphate dehydrogenase hemolytic anemia HMP pathway synthesis of riboses Transketolase dependent on TPP decrease TPP Wericks korsakoff syndrome Glucose 6 phosphate dehydrogenase deficiency is resistant to malaria Deficiency of xylitol dehydrogenase essential pentosuria GLACTOSE METABOLISM:CLASSICAL GALACTOSEMIA Infants Deficiency of galactose 1-phosphate Transferase uradyl. Increase galactitol by aldose reductae cataract diagnosis elevated galactose 1-phosphate uridyl transferase FRUCTOSE METABOLISM:Deficiency of fructokinase essential fructosuria Deficiency of aldolase-B hereditary fructose intolerance Mucopolysaccharidoses-I Iduronidase Hurlers syndrome Mucopolysaccharidoses-II iduronate sulfatase Hunters syndrome Mucopolysaccharidoses-III sanfilippo syndrome - glucuronidase sly syndrome (Mucopolysaccharidoses-VII)
USMLE Preparatory Online Resource_ Effective Biochemistry and Genetics Teaching Relatively Short Time_Dr Kumar Ponnusamy Urea Cycle & Nitrogen Metabolism_ST Matthew's University School of Medicine 2010