Veterinary Biochemistry Review 24/25 PDF

VETM 1503 Veterinary Biochemistry Review S. Bridglalsingh  Oxidoreductases Oxidation/reduction reactions: Transfer of electrons Change in oxidation state  Transferases Transfer of C-, N- or P- containing groups – moves a fu...

VETM 1503 Veterinary Biochemistry Review S. Bridglalsingh  Oxidoreductases Oxidation/reduction reactions: Transfer of electrons Change in oxidation state  Transferases Transfer of C-, N- or P- containing groups – moves a functional group from one molecule to another  Hydrolases Cleaves covalent bonds by the addition of water  Enzyme components Holoenzyme – active with non-protein part, e.g., DNA and RNA polymerases Apoenzyme – inactive without non-protein part, e.g., trypsin, pepsin Cofactor – non-protein moiety that is a metal ion, e.g., Zn2+ or Fe2+ Coenzyme – non-protein moiety that is an organic molecule required for all reactions except hydrolysis, e.g., FAD and NAD  Suicide inhibition Examples: Aspirin Allopurinol 5-fluorouracil Glucose metabolism in the mature erythrocyte Krebs Cycle  Phosphofructokinase (PFK) activity Stimulators Inhibitors AMP + ADP ATP Fructose-6-phosphate Phosphocreatine Inorganic phosphate Citrate Ammonium ion Glucagon (liver) Epinephrine (muscle) H+ ions Insulin Adenosine (muscle) Insulin Binding and Signal Pathway  Role of Carnitine Supplementation Deficiency Efficient beta oxidation Decreased beta oxidation of FA’s of FA’s Support of weight loss Steatosis Maintenance of muscle Hepatic lipidosis mass Regulation point of hepatic fatty acid biosynthesis Hormonal secretions of the Endocrine Pancreas  Activity of Lipases Milk – young animal digestion Lingual – minimal Gastric – starts fat digestion Hepatic – acts on lipoproteins Pancreatic – major fat digestive enzyme together with colipase Lipoprotein Lipase (LPL) – activated by insulin for lipogenesis Hormone Sensitive Lipase (HSL) – lipolysis from adipocytes Activated by epinephrine, thyroxine and cortisol Phospholipase A2 – generates lysophospholipids from dietary PL’s Ketonaemia Glucogenic vs. Ketogenic Amino Acids The Urea Cycle  Glutamate Body’s ammonia pool: Only amino acid undergoing oxidative deamination at a significant rate and therefore is a MAJOR contributor to the body’s ammonium ion (NH4+) pool Purine biosynthesis Clinical Enzymology/Diagnostics  Biochemistry Panel Hepatocellular injury: 1. Alanine aminotransferase/transaminase (ALT) – dogs + cats 2. Aspartate aminotransferase (AST) – large animals Mixed Hepatopathy: 1. Increased ALT 2. Increased ALP Plasma Proteins (C-reactive protein) Acute Phase Proteins  Isoenzyme Alkaline phosphatase (ALP): three distinct genetic sources, including kidney, Example of subunit arrangement for liver, bone, placental, and intestinal lactate dehydrogenase enzymes different versions of the same enzyme catalyze the same biochemical reactions have different amino acid sequences, isoelectric points (PI), electrophoretic mobility, and kinetic parameters (Km and Vmax). differ in their subunit composition and isoelectric point exhibit variations in their kinetic properties to meet the needs of various tissues.  Dysproteinaemias Definition – abnormality of the protein content of blood General causes: Congenital or acquired Protein loss Disorder of biosynthesis Haemoconcentration Increased T-cell or B-cell production of immunoglobulins (Ehrlichiosis, neoplasia)  Lipid Profile in Disease Diagnosis Serum biochemistry panel: Cholesterol Triglycerides Terms: Hyperlipidaemia – both elevated (managed with EPA + DHA) Hypercholesterolaemia – only cholesterol elevated Hypertriglyceridaemia – only triglycerides elevated  Renal Function Tests Blood urea nitrogen – protein content/haemorrhage Creatinine – phosphocreatine metabolism Symmetric dimethyl arginine (SDMA) – unaffected by muscle mass Urine specific gravity – renal concentration Urine protein creatinine ratio Urine culture and sensitivity Blood pressure Ultrasound of the urinary tract Urinalysis  3rd space fluid loss Pleural/thoracic effusion Peritoneal/abdominal effusion Injured tissue  Glycogen Storage Diseases Dogs Cats Horses  Diabetes Mellitus Blood Glucose Measurement Human Medicine Veterinary Medicine Fasting blood glucose Fasting blood glucose Glycated haemoglobin (HbA1c) Urine glucose Oral glucose tolerance test Blood fructosamine Acetone breath Blood ketones Diseases with high demand for carbohydrates leading to ketone body production Pregnancy Toxaemia Bovine Ketosis  Hypoglycaemia of baby piglets Low liver and muscle glycogen stores Low blood glucose Inadequate intake of colostrum Hypothermia Wet pens Infectious or haemolytic disease Impaired hepatic gluconeogenesis during starvation Insulinoma  Exocrine Pancreatic Insufficiency Soft to diarrhoea Yellow colour Frequent, voluminous defaecation Steatorrhea – greasy stool Ravenous appetite Weight loss  Properties of common fluids Cl- concentration Fluid Type Comments (mEq/L) higher than plasma (110) results in acidosis; recommended for 0.9% sodium chloride (saline) 154 hypochloraemic metabolic alkalosis no buffer capacity can lead to fluid overload alkalinizing contraindicated in patients with liver Lactated Ringer’s Solution 109 disease (cannot metabolize lactate) contains potassium (beware decreased renal function) alkalinizing calcium free Plasma-Lyte 103 quick correction of acidosis decreases risk of renal tubular damage closest to human plasma calcium free Normosol-R 98 similar to Plasma-Lyte Acid Base Disturbance Antioxidant Enzymes  Overview of cytochromes P450’s or CYPs Detoxification is the main role Superfamily of enzymes Haeme as a cofactor Contains a haeme-iron centre Mostly function as monooxygenases Oxidizes Steroids Fatty acids Xenobiotics Involved in hormone synthesis/breakdown  Reactive species of Phase 1 and Phase 2 pathways Good Luck!!!