ISSN: 2320-5407 Int. J. Adv. Res. 6(9), 631-654 RESEARCH
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Hyperbilirubinemia
Porphyrins Porphyrins (Porphins) are cyclic tetrapyrol compounds formed by the linkage )). of four pyrrole rings through methenyl bridges (( HC In the reduced porphyrins (Porphyrinogens) the linkage of four pyrrole rings (tetrapyrol) through methylene bridges (( CH2 )) The characteristic property of porphyrins is the formation of complexes with the metal ion bound to nitrogen atoms of the pyrrole rings. e.g. Heme (iron porphyrin). Proteins which contain heme ((hemoproteins)) are widely distributed e.g. Hemoglobin, Myoglobin, Cytochromes, Catalase & Tryptophan pyrrolase. Natural porphyrins have substituent side chains on the eight hydrogen atoms numbered on the pyrrole rings. These side chains are: CH 1-Methyl-group (M)… (( 3 )) 2-Acetate-group (A)… (( CH2COOH )) 3-Propionate-group (P)… (( CH2CH2COOH )) 4-Vinyl-group (V)… (( CH CH2 )) Porphyrins with asymmetric arrangement of the side chains are classified as type III porphyrins while those with symmetric arrangement of the side chains are classified as type I porphyrins. Only types I & III are present in nature & type III series is more important because it includes heme. 1 Heme Biosynthesis Heme biosynthesis occurs through the following steps: 1-The starting reaction is the condensation between succinyl-CoA ((derived from citric acid cycle in the mitochondria)) & glycine, this reaction is a rate limiting reaction in the hepatic heme synthesis, it occurs in the mitochondria & is catalyzed by ALA synthase (Aminolevulinate synthase) enzyme in the presence of pyridoxal phosphate as a cofactor. The product of this reaction is α-amino-β-ketoadipate which is rapidly decarboxylated to form δ-aminolevulinate (ALA). 2-In the cytoplasm condensation reaction between two molecules of ALA is catalyzed by ALA dehydratase enzyme to form two molecules of water & one 2 molecule of porphobilinogen (PBG) which is a precursor of pyrrole. -
Characterisation of Bilirubin Metabolic Pathway in Hepatic Mitochondria Siti Nur Fadzilah Muhsain M.Sc
Characterisation of Bilirubin Metabolic Pathway in Hepatic Mitochondria Siti Nur Fadzilah Muhsain M.Sc. (Medical Research) 2005 Universiti Sains Malaysia Postgrad. Dip. (Toxicology) 2003 University of Surrey B.Sc.(Biomed. Sc.) 2000 Universiti Putra Malaysia A thesis submitted for the degree of Doctor of Philosophy at The University of Queensland in 2014 School of Medicine ABSTRACT Bilirubin (BR), a toxic waste product of degraded haem, is a potent antioxidant at physiological concentrations. To achieve the maximum benefit of BR, its intracellular level needs to be carefully regulated. A system comprising of two enzymes, haem oxygenase-1 (HMOX1) and cytochrome P450 2A5 (CYP2A5) exists in the endoplasmic reticulum (ER), responsible for regulating BR homeostasis. This system is induced in response to oxidative stress. In this thesis, oxidative stress caused accumulation of these enzymes in mitochondria — major producers and targets of reactive oxygen species (ROS) — is demonstrated. To understand the significance of this intracellular targeting, properties of microsomal and mitochondrial BR metabolising enzymes were compared and the capacity of mitochondrial CYP2A5 to oxidise BR in response to oxidative stress is reported. Microsomes and mitochondrial fractions were isolated from liver homogenates of DBA/2J mice, administered with sub-toxic dose of pyrazole, an oxidant stressor. The purity of extracted organelles was determined by analysing the expressions and activities of their respective marker enzymes. HMOX1 and CYP2A5 were significantly increased in microsomes and even more so in mitochondria in response to pyrazole-induced oxidative stress. By contrast, the treatment did not increase either microsomes or mitochondrial Uridine-diphosphate-glucuronosyltransferase 1A1 (UGT1A1), the sole enzyme that catalyses BR elimination through glucuronidation. -
Porphyrins & Bile Pigments
Bio. 2. ASPU. Lectu.6. Prof. Dr. F. ALQuobaili Porphyrins & Bile Pigments • Biomedical Importance These topics are closely related, because heme is synthesized from porphyrins and iron, and the products of degradation of heme are the bile pigments and iron. Knowledge of the biochemistry of the porphyrins and of heme is basic to understanding the varied functions of hemoproteins in the body. The porphyrias are a group of diseases caused by abnormalities in the pathway of biosynthesis of the various porphyrins. A much more prevalent clinical condition is jaundice, due to elevation of bilirubin in the plasma, due to overproduction of bilirubin or to failure of its excretion and is seen in numerous diseases ranging from hemolytic anemias to viral hepatitis and to cancer of the pancreas. • Metalloporphyrins & Hemoproteins Are Important in Nature Porphyrins are cyclic compounds formed by the linkage of four pyrrole rings through methyne (==HC—) bridges. A characteristic property of the porphyrins is the formation of complexes with metal ions bound to the nitrogen atom of the pyrrole rings. Examples are the iron porphyrins such as heme of hemoglobin and the magnesium‐containing porphyrin chlorophyll, the photosynthetic pigment of plants. • Natural Porphyrins Have Substituent Side Chains on the Porphin Nucleus The porphyrins found in nature are compounds in which various side chains are substituted for the eight hydrogen atoms numbered in the porphyrin nucleus. As a simple means of showing these substitutions, Fischer proposed a shorthand formula in which the methyne bridges are omitted and a porphyrin with this type of asymmetric substitution is classified as a type III porphyrin. -
Bilirubin Metabolism (Lecture 8)
Bilirubin Metabolism (Lecture 8) Excretory function of bile Bile is a medium for excretion of many substances as bile pigments, cholesterol, many drugs, toxins and various organic substances as copper and zinc. These substances are then eliminated in the feces. One of these substances excreted in bile is the greenish yellow pigment bilirubin. This is a major end product of hemoglobin degradation. It’s highly soluble in all cell membranes & is also very toxic. Therefore, its excretion in the bile is one of the very important functions of the liver. FATE OF RED BLOOD CELLS Life span of RBCs in blood stream is 60-120 days. Senescent RBCs become too fragile to exist longer in the circulatory system, their cell membranes rupture and they are phagocytosed and/or lysed. Normally, lysis occurs extravascularly in the reticuloendothelial system subsequent to RBC phagocytosis. Lysis can also occur intravascularly (in blood stream). The hemoglobin is first split into globin & heme. The AA formed from breakdown of globin are stored in the body. Metabolism of bilirubin The heme ring is opened to give: 1. Free iron that is transported in the blood by transferrin and stored in the body as a reservoir for erythropoiesis. 2. Bile pigments: The 1st pigment is biliverdin but it is rapidly reduced by biliverdin reductase to free bilirubin which is gradually released into the plasma. The free bilirubin is hydrophobic, immediately combines with plasma proteins (mainly albumin and globulin) forming a water soluble compound called hemobilirubin (unconjugated bilirubin) which is rapidly transported to hepatocytes for further metabolism. Even when bound to albumin it’s called free bilirubin. -
Biochemistry I Enzymes
BIOCHEMISTRY I 3rd. Stage Lec. ENZYMES Biomedical Importance: Enzymes, which catalyze the biochemical reactions, are essential for life. They participate in the breakdown of nutrients to supply energy and chemical building blocks; the assembly of those building blocks into proteins, DNA, membranes, cells, and tissues; and the harnessing of energy to power cell motility, neural function, and muscle contraction. The vast majority of enzymes are proteins. Notable exceptions include ribosomal RNAs and a handful of RNA molecules imbued with endonuclease or nucleotide ligase activity known collectively as ribozymes. The ability to detect and to quantify the activity of specific enzymes in blood, other tissue fluids, or cell extracts provides information that complements the physician’s ability to diagnose and predict the prognosis of many diseases. Further medical applications include changes in the quantity or in the catalytic activity of key enzymes that can result from genetic defects, nutritional deficits, tissue damage, toxins, or infection by viral or bacterial pathogens (eg, Vibrio cholerae). Medical scientists address imbalances in enzyme activity by using pharmacologic agents to inhibit specific enzymes and are investigating gene therapy as a means to remedy deficits in enzyme level or function. In addition to serving as the catalysts for all metabolic processes, their impressive catalytic activity, substrate specificity, and stereospecificity enable enzymes to fulfill key roles in additional processes related to human health and well-being. Proteases and amylases augment the capacity of detergents to remove dirt and stains, and enzymes play important roles in producing or enhancing the nutrient value of food products for both humans and animals. -
NEONATAL Hb, O2-TRANSPORT & JAUNDICE: OVERVIEW
BILIRUBIN METABOLISM & JAUNDICE UNIVERSITY OF PNG SCHOOL OF MEDICINE AND HEALTH SCIENCES DISCIPLINE OF BIOCHEMISTRY & MOLECULAR BIOLOGY PBL MBBS II SEMINAR VJ Temple 1 Brief description of Hemoglobin (Hb) structure • Hemoglobin (Hb): Made up of 4-Subunits (Tetramer) held together by multiple non-covalent interactions; • Each subunit consist of: • Heme (Ferro-Protoporphyrin), • Globin protein; • Heme: Protoporphyrin IX and Ferrous ion (Fe2); • Globin protein folds around Heme group forming a protective Hydrophobic pocket; • Heme is the site of Oxygen binding; 2 • There are different types of Hemoglobin, with different subunits: • Foetal Hemoglobin (Hb F): 2 2 Two types of Adult Hemoglobin (Hb A): • Hb A1 represented as: 2 2 • It is the major (98%) form of Hb in adults; • Hb A2 represented as: 2 2 • It is the minor (2%) form of Hb in adults; 3 What are the major sources of Heme in humans? • RBC is major source of Heme in humans, • Life span of RBC is about 120 days, • Other sources of Heme include: • Myoglobin (Mb): Stores Oxygen in muscle cells, • Cytochromes: present in some enzymes, • Catalase: an enzyme, 4 What normally happens to RBC after 120 days? • RBC is destroyed mainly in Reticuloendothelial system (Extra-vascular system: Spleen and Liver); • Daily turnover of Hb is about 6 g/day; • Hb is broken down, • Globin protein is hydrolyzed to amino acids, • Protoporphyrin Ring in Heme is Hydrophobic, thus must be made soluble before it is excreted, • Ferrous ion is removed and stored in Iron pool, for reuse, • Protoporphyrin ring is metabolized -
Bilirubin Metabolism
Bilirubin Metabolism By Aseel .j.abdullah Introduction • Bilirubin is the orange-yellow pigment derived from senescent red blood cells. • It is a toxic waste product in the body. • It is extracted and biotransformed mainly in the liver, and excreted in bile and urine. • It is a bile pigment • Elevations in serum and urine bilirubin levels are normally associated with Jaundice. Erythrocytes become “old” as they lose their flexibility and increasingly rigid and fragile,they easily destruct during passage through tight circulation spots, especially in spleen, where the intra-capillary space is about 3 micron as compared to 8 micron of cell size RBCs useful life span is 100 to 120 days,After which they become trapped and fragment in smaller circulatory channels, particularly in those of the spleen. For this reason, the spleen is sometimes called the “red blood cell graveyard.” Dying erythrocytes are engulfed and destroyed by macrophages. Formation of Bilirubin • Primary site of synthesis:- SPLEEN : The Graveyard of Red Blood Cells • Secondary site of synthesis:- LIVER & BONE MARROW Pathophysiology RBCs Breakdown Hemoglobin Produces & Breakdown Heme Heme Oxygenase Biliverdin Biliverdin Reductase Bilirubin In Blood Unconjugated bilirubin • The bilirubin synthesized in – Lipid soluble spleen, liver & bone marrow – : limits excretion is unconjugated bilirubin. – 1 gm albumin binds 8.5 mg bilirubin • It is hydrophobic in nature so – Fatty acids & drugs can it is transported to the liver displace bilirubin as a complex with the – Indirect positive reaction plasma protein, albumin. in van den Bergh test • Most of the reabsorbed urobilinogen is taken up by the liver & is re-excreted in the bile. -
Bilirubin PDF 12Days
Bilirubin Physiology – WYNTKFTB • Bilirubin metabolism – Unconjugated – Conjugation – Excretion • Enterohepatic circulation • Implication of bilirubin metabolism – Urine – Stool • Understand the metabolic pathway as related to the disease state of JAUNDICE Don’t make me come up there and steal your google machines! BR - Alb Thank you. BG the Bilirubin an overview by howard sachs Slo-Motion Instant Replay… Heme oxygenase Biliverdin Reductase Heme oxygenase Biliverdin Reductase Bilirubin Albumin (unconjugated) …not water soluble… Unconjugated Bilirubin (‘Indirect’) Key points: • ‘Attached to albumin’: too big to pass through glomerular filtration barrier. • Intravascular: Hemoglobin ® urine • Unconjugated: not water soluble. How can we get too much unconjugated bilirubin in the serum? 1. Hemolysis • Elevated indirect bilirubin is used as a diagnostic marker (with LDH, ¯ haptoglobin) 2. Conjugation defect: inherited (Gilbert’s, Crigler-Najjar) Multidrug resistance associated protein Bilirubin binds to cytosolic binding protein, glutathione s-transferase (GST) for transport to ER Conjugation of bilirubin is catalyzed by bilirubin-uridinediphosphate (UDP)- glucuronosyltransferase (UGT1A1). Product is bilirubin diglucuronide. UDPGA is the donor sugar Multidrug resistance Endoplasmic reticulum associated protein Bilirubin diglucuronide Conjugated (direct) Bilirubin binds to cytosolic binding protein, glutathione s-transferase (GST) for transport to ER Conjugation of bilirubin is catalyzed by bilirubin-uridinediphosphate (UDP)- glucuronosyltransferase -
16Th March 2020 Blood Revised
Blood is the fluid circulating in a closed system of blood vessels and the chambers of the heart It is the medium which transports substances from one part of the body to the other Blood is composed of Plasma Platelets Cells WBCs RBCs (Erythrocytes) Hemoglobin (Hb) is red , oxygen carrying pigment present exclusively in erythrocytes HEMOGLOBIN A conjugated protein containing Globin Protein part ( 4 polypeptide chains- ) 96% of the total Hb mass Varies from species to species( species specificity) Heme Non protein (prosthetic group) Red colour Iron containing tetrapyrrole porphyrin derivative 4% of the total Hb mass Reversibly binds Oxygen Structure of Heme An Iron –porphyrin (Protoporphrin IX) compound with tetrapyrrole structure Protoporphyrin IX consists of 4 pyrrole rings combined through — CH= bridges (methyne bridges) The methyne bridges are referred as α,β,γ, and δ. The 2 Hydrogen atoms in the –NH groups pyrrole rings (II & IV) are replaced by Ferrous( Fe++) . The four pyrrole rings present in the porphyrin molecule are designated as I,II,III & IV . Each of these four rings has 2 groups attached to them M = Methyl –CH3 V = Vinyl – CH=CH2 P = Propionyl - CH2 - CH2 - COOH . The Fe++ can form 2 additional bonds .One of these position is linked internally (5th linkage ) to nitrogen of imidazole ring of Histidine of the Globin polypeptide chains . Other position is available to bind Oxygen Heme is the most prevalent metalloporphyrin in humans Common prosthetic group in Hemoglobin — Transport of O2 in blood Myoglobin — Storage of O2 in muscles Cytochromes — Part of electron transport chain Catalase — Degradation of H2O2 Tryptophan pyrolase — Oxidation of Tryptophan Cytochrome P450 — Hydroxylation of Xenobiotics HEME SYNTHESIS Major sites Liver Erythrocyte producing cells of bone marrow Rate of heme synthesis in liver is highly variable & depends upon size of heme pool while it is relatively constant in in bone marrow is relatively constant Mature RBC lack mitochondria and are unable to synthesize heme. -
(12) Patent Application Publication (10) Pub. No.: US 2001/0034023 A1 Stanton, JR
US 2001.0034O23A1. (19) United States (12) Patent Application Publication (10) Pub. No.: US 2001/0034023 A1 Stanton, JR. et al. (43) Pub. Date: Oct. 25, 2001 (54) GENE SEQUENCE VARIATIONS WITH Related U.S. Application Data UTILITY IN DETERMINING THE (63) Continuation-in-part of application No. 09/710,467, TREATMENT OF DISEASE, INGENES filed on Nov. 8, 2000, which is a continuation-in-part RELATING TO DRUG PROCESSING of application No. 09/696,482, filed on Oct. 24, 2000. Non-provisional of provisional application No. 60/131,334, filed on Apr. 26, 1999. Non-provisional (76) Inventors: Vincent P. Stanton JR., Belmont, MA of provisional application No. 60/139,440, filed on (US); Martin Zillmann, Shrewsbury, Jun. 15, 1999. MA (US) (30) Foreign Application Priority Data Correspondence Address: Jan. 20, 2000 (WO)........................... PCT/USOO/O1392 EDWARD O. KRUESSER BROBECK PHLEGER & HARRISON Publication Classification 12390 EL CAMINO REAL (51) Int. Cl. ............................. C12O 1/68; G06F 19/00 SAN DIEGO, CA 92130 (US) (52) U.S. Cl. ................................................... 435/6; 702/20 (57) ABSTRACT (21) Appl. No.: 09/733,000 Methods for identifying and utilizing variances in genes relating to efficacy and Safety of medical therapy and other aspects of medical therapy are described, including methods (22) Filed: Dec. 7, 2000 for Selecting an effective treatment. US 2001/0034023 A1 Oct. 25, 2001 GENE SEQUENCE WARIATIONS WITH UTILITY 0005 For some drugs, over 90% of the measurable IN DETERMINING THE TREATMENT OF interSubject variation in Selected pharmacokinetic param DISEASE, INGENES RELATING TO DRUG eters has been shown to be heritable. For a limited number PROCESSING of drugs, DNA sequence variances have been identified in Specific genes that are involved in drug action or metabo RELATED APPLICATIONS lism, and these variances have been shown to account for the 0001. -
About Wales' Pathology Handbook
Aneurin Bevan University Health Board About Wales' Pathology Handbook Wales Pathology Handbook (WPH) is a knowledge service within the Welsh national information architecture. It provides national and local catalogues of requestable tests, rules and guidance for electronic requesting (via the Welsh Clinical Portal (WCP) and GP systems) and a web-based knowledge resource for all clinical staff. The introduction of the new national Laboratory Information Management System (LIMS) for Wales means that the operational WPH needs to be reviewed and updated to ensure that it is fit for purpose in the future environment. Page 1 of 697 Date Created - Monday, September 27, 2021 Aneurin Bevan University Health Board Departments Andrology Blood Sciences Cytology Histopathology Microbiology Mortuary Services Transfusion Page 2 of 697 Date Created - Monday, September 27, 2021 Aneurin Bevan University Health Board Andrology Department Information PLEASE NOTE: THE PATHOLOGY HANDBOOK INFORMATION BELOW IS ONLY VALID AT THE TIME OF ACCESS, PRINTED COPIES MUST NOT BE USED Andrology services available are: Semen analysis for fertility investigations. Semen analysis following a vasectomy. Retrograde Ejaculation Investigation. Andrology work is carried out within the Andrology Department, Pathology at Nevill Hall Hospital. Lead Andrologist: Mrs Karen Llewelyn (01873 733062). Deputy Lead: Mrs Ruth Lancaster (01873 733062). Department Manager: Mr Julian Bendle (01633 234502). Please Scroll or Page Down for additional information relating to telephone numbers, sample requesting and collection. ROUTINE OPENING TIMES Nevill Hall site: Andrology Service Monday to Friday: 9:00am - 5:00pm Semen samples for Fertility analysis, Vasectomy analysis or Retrograde Ejaculation Investigation are processed by appointment only. Any sample booked without an appointment will not be tested. -
OPNF Hyperbilirubinemia Presentation
OPNF Hyperbilirubinemia Presentation 1) Definitions: a) Jaundice: _____________ discoloration of the skin and sclera caused by an elevated _________ level. b) Bilirubin: Metabolic end product of ____ breakdown. c) Always assess for jaundice in good lighting. Jaundice is not a reliable indicator for bilirubin level. 2) Bilirubin Physiology: a) Synthesis: Red blood cell breakdown Heme Biliverdin Bilirubin b) Bilirubin is _____ soluble. c) Transport: Bilirubin Free floating OR binds to Albumin and transports directly to the liver Taken up into the hepatocytes d) Metabolism (conjugation): Bilirubin is converted and becomes _____ soluble and secreted into bile and excreted then into the digestive track. e) Clearance/Excretion: i) Conjugated bilirubin changes into urobilinogen and excretes in urine. ii) Urobilinogen converts into stercobilinogen and excreted in the stool f) Enterohepatic circulation: Beta-glucuronidase from the lining of the small intestine deconjugates the bilirubin allowing it to be reabsorbed into circulation 3) Basics of Hyperbilirubinemia: a) Hyperbilirubinemia: _________ ___________ _________________ b) Physiologic Pathologic Jaundice after 24-48hr Jaundice within the first 24hr Requires no treatment Requires evaluation & treatment Peak: Day 3 in term, Day 5-6 in preterm Bili increases > 5mg/dL each day Resolved by 14 days of life Jaundice lasting longer than 14 days Normal infant appearance Can be anemic, discolored stools/urine Normal physiology of increased RBC Cause varies, any process that is destruction, reduced hepatic uptake, exaggerated enterohepatic reabsorption & decreased clearance c) Causes of Hyperbilirubinemia: i) Increased bilirubin production ii) Increased enterohepatic circulation iii) Decreased clearance of unconjugated bilirubin iv) Metabolic conditions v) Inborn errors of metabolism 4) Diagnosis a) Gold standard is the ___________________ which is the plasma level of bilirubin bound to albumin.