Biochemistry المعلومات بالداخل موثوق بها لأنها مراجعه و معتمده من Certified from Pharmacists_coffee magazine
Drug biotransformation: takes place in almost any tissue in the body, the most important being the liver. The most important site within the liver cells is the smooth endoplasmic reticulum. This is a thin tubular network inside the cell that participates in biotransformation. (When the liver is homogenized, the endoplasmic reticulum is broken up into microsomes).
In a competitive enzymatic reaction , the rate of the reaction is not affected by the addition of more substrate (E + S ES – P).
Enzymes (apoproteins): these are protein in nature, used to catalyze biological reactions.
Ligase enzyme: rebuilds DNA which has been destroyed.
Amylase: is a pancreatic enzyme involved in the breakdown of starch. It is elevated in acute pancreatitis.
Chymopapin: is a proteolytic enzyme used to treat herniated lower back disks.
Pancrease: is most commonly used in patients suffering from:
Cystic fibrosis of pancreas.
Ligases: are one of the 6 main classes of enzymes. These enzymes catalyze the formation of bonds between 2 substrate molecules coupled with the hydrolysis of pyrophosphate bond in ATP or similar energy donor.
Protein Kinase: is activated by cyclic AMP (cAMP) & has regulatory subunits; its function is limited by some enzymes.
Phases of metabolism: there are 2 phases of metabolism
Phase I: Involves microsomal enzymes, catalyzed by cytochromes which may activate, inactivate or leave activity of drug unchanged. It includes metabolism by: aliphatic oxidation, sulfo-oxidation, N-oxidation, oxidative dealkylation, oxidative deamination, aromatic hydroxylation, N-dealkylation, S-demethylation, N-dehydroxylation, (Oxidation, reduction, hydroxylation, hydrolysis, deamination or demethylation).
Phase II: involves cytoplasmic & microsomal enzymes (separately or in combination) - deactivation of drugs by conjugation (with glucouronic acid, glycine or glutamine), acetylation, methylation or sulfation.
Mechanism of acetylation of the amino gp: is through Acetyl-Co-A + acetyl transferase
The typical cell contains the endoplasmic reticulum, responsible for the degradation of HB.
Cytochrome P 450: is associated with the extra-mitochondrial electron transfer in the liver, involved in “Mixed Function Oxidation” reaction in the liver & drug detoxication. It is an iron-protoprophyrin cellular pigment.
Cytoplasmic enzymes involved in biotransformation are oxidases (alcohol dehydrogenase), sulfatase, acyl transferase + mitochondrial enzymes (MAO & aldehyde dehydrogenase).
R–CH 2 –NH 2 R–CO–NH 2 R–CHO + NH 3 (the reaction is oxidative deamination)
Plasma protein binding: If drug B has greater affinity ( er association constant) for a specific protein binding site than drug A. It will displace it. The larger the dose of drug B the greater the displacement (competitive reaction).
50% of normal plasma protein is albumin.
Examples of pro-drugs include: Enalapril, L-dopa, Acetaminophen, Prednisone.
Hemoglobin: is made of 4 protein chain subunits (globulins), each chain containing one haem moiety. Haem consists of a tetra-pyrrole prophyrin ring containing Fe. Each haem can carry an oxygen molecule.
Sucrose (a disaccharide): upon hydrolysis glucose + fructose.
Glucose & carbohydrate metabolism:
Under aerobic conditions (via Kreb’s cycle) CO 2 + H 2 O (end products)
Under anaerobic conditions (anaerobic glycolysis) Lactic acid (end products)
Fat metabolism: the end products are CO 2 & H 2 O.
Protein metabolism: proteins are polymers of amino acids
Metabolism of the nitrogen portion Urea (end
Metabolism of the hydrocarbon portion CO 2 + H 2 O products)
In diabetic patients (insulin deficiency) protein is converted to glucose (gluconeogenesis) weight loss. [Insulin inhibits gluconeogenesis]
Barbiturates ( & their analogues e.g. glutathemide) induce liver microsomal enzyme system & increase liver biotransformation.
When used chronically the dose of barbiturates should be increased (tolerance).
Phenobarbitone is used in the treatment of drug induced jaundice because it enhances glucoronide conjugation through induction of the microsomal enzyme system in the liver which enhances the production of bilirubin-binding Y protein.
Phenytoin induces the liver microsomal enzyme system disturbs folic acid metabolism.
Disulfuram & Metronidazole: inhibit the metabolism of alcohol by inhibiting the alcohol dehydrogenase enzyme. Such drugs should not be given with alcohol because of the possibility of inducing disulfuram like reactions by inhibiting oxidation of acetaldehyde.
A substance that exists naturally in the body is called endogenous / endogenic.
Enkephalins: these are thought to be opiate-like peptides, localized in nerve endings.
Endorphins: endorphin is the closest to morphine in action.
Histamine: stimulates gastric secretions.
Insulin: is the hormone that acts on the cell membrane.
Adjustment of the pH of body fluids: the immediate local adjustment of pH in body fluids is accomplished by buffers but the eventual disposition of acid (H + ) is accomplished by lungs & kidney (i.e. the regulation of acidosis is 1 st through the blood followed by lungs & kidney).