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Global instit

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  • 1. The medical biochemistry – FMGEB2 – 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 deficiencyNIACIN:-  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)PYRIDOXINE:- B6  Coenzyme – pyridoxine, pyridoxal pyridoxamine  Pyridoxine used in transamination, decarboxylation, deamination.  Active form is pyridoxal phosphate (PLP) transaminationIt is required for the production of the monoamine neurotransmittersserotonin, dopamine, norepinephrine and epinephrine, as it is the precursorto pyridoxal phosphate: cofactor for the enzyme aromatic amino aciddecarboxylase. This enzyme is responsible for converting the precursors 5-hydroxytryptophan (5-HTP) into serotonin and levodopa (L-DOPA) intodopamine, noradrenaline and adrenaline. As such it has been implicated inthe 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.Global institute of medical sciences www.gims-org.com
  • 2. The medical biochemistry – FMGEBIOTIN – B7It is required for carboxylation reactionsEg.:- 1. acetyl CoA carboxylase 2. propony CoA carboxylase 3. pyruvate carboxylasePANTOTHENIC ACID:-  also known as coenzyme –A  deficiency – burning feet syndromeFOLIC 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)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)Global institute of medical sciences www.gims-org.com
  • 3. The medical biochemistry – FMGE  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 – α2,β2 – HbA1  Fetal hemoglobin – α2 γ2 – HbF  HbA2 – α2 δ2  Glycosylated hemoglobin – Hb A1 C – α2 β2 –glucose (diabetes)  Fetal Hb has more affinity towards O2 than adult – HbF – 100% ; HbA1 – 95%.  In heme if Fe2+ oxidizes to form Fe3+ known methehemoglobinBIOSYNTHESIS OF HEME:-  Heme synthesis take place in liver  ALA synthase is rate limiting step in heme biosynthesisGlobal institute of medical sciences www.gims-org.com
  • 4. The medical biochemistry – FMGEHEME METABOLISM :-  Bilirubin bound to albumin to form bilirubin albumin complexGlobal institute of medical sciences www.gims-org.com
  • 5. The medical biochemistry – FMGE  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 hepatocytesPorphyrias :-Global institute of medical sciences www.gims-org.com
  • 6. The medical biochemistry – FMGECARBOHYDRATE METABOLISM:-  Insulin dependent glucose transport – GLIT-4 skeletal muscle, adipose tissue  GLUT-1 – erythrocytesGLYCOLYSIS CYCLE:-Global institute of medical sciences www.gims-org.com
  • 7. The medical biochemistry – FMGE  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 anerobicIRREVERSIBLE STEPS:-  Hexokinase  PFK-1  Pyruvate kinase ( deficiency hemolytic anemia )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 poisoningTCA CYCLE:-Global institute of medical sciences www.gims-org.com
  • 8. The medical biochemistry – FMGE  Location – mitochondria  Citrate synthase - rate limitin step  NADH produce in :- 1. iso citrate dehydrogenase 2. α-ketoglutarate dehydrogenase 3. malate dehydrogenase  FADH produced by succinate dehydrogenase  GTP produced by succinate thiokinaseINHIBITORS:- 1. Aconitase – fluroacetate 2. Α-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 carboxylaseGlobal institute of medical sciences www.gims-org.com
  • 9. The medical biochemistry – FMGE  Alanin glucogenic aminoacid  Glucagon stimulates gluconeogenesis, insulin inhibits  Αlpha- cells secrets glucagone  Alcohol inhibits gluconeogenesis induces hypoglycemiaGLYCOGEN 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 synthesisGlobal institute of medical sciences www.gims-org.com
  • 10. The medical biochemistry – FMGE  Glycogen phosphorylase breaks glycogen at α1-4 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 Girek’s disease  Lysosomal α (1, 4) glucosidase deficiency – Pompe’s disease – heart is more commonly involved – death occurs due to heart failure.  De-branching enzyme deficiency Anderson’s disease  Muscle glycogen phosphorylase deficiency –MC Ardle’s disease  Liver glycogen phosphorylase Her’s disease  Phosphofructokinase – Taruri’s disease – erythocytes, hemolysisHMP 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 – Werick’s korsakoff syndrome  Glucose 6 phosphate dehydrogenase deficiency is resistant to malaria  Deficiency of xylitol dehydrogenase – essential pentosuriaGLACTOSE METABOLISM:-  CLASSICAL GALACTOSEMIA  Infants  Deficiency of galactose 1-phosphate Transferase uradyl.  Increase galactitol by aldose reductae – cataract diagnosis – elevated galactose 1-phosphate uridyl transferaseFRUCTOSE METABOLISM:-  Deficiency of fructokinase essential fructosuria  Deficiency of aldolase-B hereditary fructose intolerance  Mucopolysaccharidoses-I – Iduronidase – Hurler’s syndrome  Mucopolysaccharidoses-II – iduronate sulfatase – Hunter’s syndrome  Mucopolysaccharidoses-III – sanfilippo syndrome  β- glucuronidase – sly syndrome (Mucopolysaccharidoses-VII)Global institute of medical sciences www.gims-org.com