BIOCHEMISTRY, BIOMEDICINE & PHARMACEUTICS

Similar to most metabolic pathways, glucose synthesis and breakdown is regulated by three different mechanisms : a) Allosteric regulators b) Covalent modification c) Changes in gene expression Regulation of glycolytic pathway: As described on the previous page and in figure 1, glycolysis is regulated by three irreversible enzymes namely : Hexokinase / glucokinase, Phosphofructokinase, and Pyruvate kinase. Figure 1: Allosteric Regulators of Glycolysis and Gluconeogenesis  Hexokinase / glucokinase: Hexokinase is a ubiquitously expressed enzyme that sets the pace of glycolysis. Hexokinase has a high affinity for glucose and transfers a negatively charged phosphate group to a glucose molecule. This step traps the glucose inside the cells and funnels it into various metabolic pathways. The high concentration of glucose-6-phosphate signals that the cell no longer requires energy or other biosynthetic pathways, and inhibits enzyme hexokinase. Glucokinase is expres...

PBL case objective a)Differential Diagnosis of Jaundice b)Biochemical basis for the diagnosis of acute liver disease c) Biochemical basis for the diagnosis of obstructive jaundice Clinical case 1:  A 52-year-old male patient arrived at the medical facility with complaints of nausea, vomiting, abdominal pain, and yellowing of the skin (icteric jaundice) that had persisted for one week. Upon conducting a physical examination, the patient was found to have stable vital signs, and there were no signs of hepatic encephalopathy (a condition affecting brain function due to liver disease). The patient exhibited yellowing of the sclera (the white part of the eyes) and tenderness in the right upper quadrant of the abdomen when touched. The laboratory investigation results are presented below. Total serum Bilirubin - 15.4 mg/dL Direct bilirubun-11.5 mg/dl Aspartate transaminase- 720 U/L Alanine transaminase - 1625 U/L Alkaline Phosphatase- 211 U/L Total Protein- 7.3 g/dl...

PBL Case Objective a) Describe how alcohol is metabolized in the body. b) Discuss the cause of hematological abnormalities if any. c) Discuss how biochemical results correlate with the provisional diagnosis. d) Discuss any test recommendations. e) Discuss the provisional diagnosis. Clinical Presentation A 40 years old man was admitted to the hospital with hematemesis, loss of consciousness, and swelling of lower limbs. The patient had a history of alcoholism with daily consumption of approximately 1 to 2 L of beer every day for the past ten years. the physical examination showed hepatomegaly and mild ascites. The hematological and biochemical results are presented below. Discussions Alcohol Metabolism occurs in the liver. The liver is the major tissue for alcohol metabolism in the body. Before alcohol reaches the liver, the alcohol dehydrogenase isoform present in the stomach metabolizes a minor quantity of alcohol.  The quantity of alcohol metabolized in ...

Case objective a) Discuss an overview of bilirubin metabolism b) Discuss neonatal physiological jaundice c) Discuss inborn errors of bilirubin metabolism d) Discuss biochemical/molecular diagnosis Case Presentation : A 48-year-old woman had a history of jaundice for decades, with no related symptoms. A laparoscopic evaluation showed a smooth liver with normal consistency and morphologic features but with a grossly black appearance. A biopsy specimen revealed coarse, deep-brown, pigmented granules on periodic acid–Schiff staining primarily at the canalicular pole of the hepatocytes and especially in the pericentral zones.  The laboratory investigation results are given below: Serum Total bilirubin - 4.6 mg/dL Direct-reacting bilirubin - 2.4 mg/dL Aspartate transaminase - 38 U/L Alanine transaminase - 25 U/L Alkaline phosphatase - 45 U/L Serum Albumin- 4.2 gm/dL Prothrombin time- 12 seconds Expression of the multidrug resistance associated protein 2 (MRP2) was ab...

                  Pathogenesis, Diagnosis, and treatment of Malaria Malaria : -  A mosquito-borne infectious disease caused by the bite of a mosquito that carries the parasitic protozoa called Plasmodium species - The disease can be fatal and life-threatening for humans, transmitted to humans through the bite of infected female Anopheles mosquitoes. - Plasmodium species comes under the parasite group called "Sporozoa" - Malaria is one of the major zoonotic diseases that cause millions of human deaths each year - It is a major public health concern, especially in tropical and subtropical regions. More than 75% of deaths occur in the African region of the world, over a million people mostly children die from malaria each year worldwide Plasmodium species: - Malaria is a vector-borne infection that is spread through the bite of the mosquito, thus the term given for this type of infection is a 'zoonotic disease'. The infected...

Gluconeogenesis is the metabolic pathway through which glucose is synthesized from a non-glucose (carbohydrate) precursors including pyruvate, lactate, and amino acids. Pyruvate and Lactate: The precursor of gluconeogenesis is primarily pyruvate. Pyruvate is the end product of glycolysis which can be further metabolized to either acetyl CoA or lactate. The conversion of pyruvate to these products depends on tissue type, ATP status, and regulatory effector molecules. The conversion of pyruvate to acetyl CoA is an irreversible step that is catalyzed by the enzyme pyruvate dehydrogenase that occurs mainly in oxidative tissues such as the liver, cardiac muscle.  In contrast, the conversion of pyruvate to lactate is a reversible step catalyzed by lactate dehydrogenase that occurs mainly in non-oxidative tissues such as red blood cells. The lactate dehydrogenase is also present in skeletal muscle that converts pyruvate to lactate during vigorous exercise. Figure 1 : Fates of Py...

Introduction to Pentose Phosphate Pathway The pentose phosphate pathway ( Hexose monophosphate pathway ) is the metabolic pathway that occurs in the cytosol and generates NADPH (nicotinamide adenine dinucleotide phosphate) which is utilized in various biosynthetic pathways. This pathway can be broadly classified into two phases i.e oxidative phase and non-oxidative phase.  In the oxidative stage of the pentose phosphate pathway, the glucose-6-phosphate is converted to five carbon ribulose-5 phosphate with generation of NADPH.  During the non-oxidative stage, the interconversion of pentose sugars and hexose sugars is catalyzed by isomerases and aldolases. The fate of these reversible steps depends on the anabolic and energy status of the cells.  The two primary functions of the pentose phosphate pathway are ; a) Provide NADPH (a coenzyme) for biosynthetic pathways b) Provide pentose sugars for nucleotides (DNA and RNA) synthesis Two phases of Pentose phosphat...

       Lesch Nyhan Syndrome: Clinical Presentation and Biochemical Diagnosis A 3-year-old child was brought to the hospital with a complaint of self-mutilation. He had a chronic ulcer on the buccal surface of his lips, and self-inflicted trauma by biting his finger. History revealed that severe motor retardation was apparent at the age 6 months old and he has never been able to lift or support his trunk.  The growth chart showed that he has growth retardation. Biochemical analysis was performed which is represented below : Serum Uric acid: 9.0 mg/dL Blood Urea : 32 mg/dL Serum Sodium : 139 mmol/l Potassium: 5.1 mmol/l Calcium 39 mmol/l Total Protein: 70 g/L Albumin: 23 g/L Urinary Uric acid: 160mg/100 ml Urinary Glucose: Absent Urinary Protein: Absent Microscopic urine examination: triphosphate crystals Diagnosis? Provisional Diagnosis : Based on the behavioral pattern of self-mutilation, growth retardation, dystonia, and increased serum and ...

Metabolic Pathway of Methionine and Cysteine Conversion of Methionine to S-Adenosyl Methionine  - Methionine is a nutritionally essential amino acid, therefore, the dietary source is generally proteins.  - S-adenosyl methionine synthase catalyzes the conversion of methionine to S-adenosyl methionine - Require ATP, the ATP is hydrolyzed to AMP and PPi, therefore two energy equivalent of ATP is consumed in the reaction Figure 1: Metabolic Pathway for the methionine metabolism Formation of S-Adenosyl homocysteine from S-Adenosyl methionine  - S-adenosyl methionine serves as an active methyl group donor in various metabolic pathways including amino acid metabolism, hormones/neurotransmitter synthesis, etc. - Once the methyl group is transferred to the methyl acceptor, the S-Adenosyl methionine is formed  - Generally transferred by specific methyltransferase Hydrolysis of S-Adenosyl homocysteine to form homocysteine  -The hydrolysis of S-Adenosyl homocysteine form...

  Metabolic Pathway for Phenylalanine and Tyrosine  ( For MCQ Practice click here ) Conversion of Phenylalanine to Tyrosine  - Phenylalanine hydroxylase (PAH) converts phenylalanine to tyrosine  - PAH is encoded by the PAH gene located in Chromosome 12 and consist of 13 exons  - Tetrameters with each monomer consisting of the catalytic site, regulator site, and subunit binding domain  - Phenylalanine hydroxylase is tetrahydrobiopterin (BH4) requiring enzyme  - Dihydrobioteridine reductase catalyzes the conversion of dihydrobiopteridine to tetrahydrobiopterin  - Deficiency of enzyme caused phenylketonuria  Figure- Overview of Phenylalanine and Tyrosine Metabolism   Transamination of Tyrosine  - Tyrosine aminotransferase catalyzes the conversion to tyrosine to p-hydroxyphenylpyruvate  - Tyrosine aminotransferase is a Pyridoxal-5-phosphate requiring enzyme  - In the process, alpha-ketoglutarate is converted into glutama...

Overview of the Heme Metabolism In this page, we will review the biological importance of heme, heme biosynthesis, regulation of heme synthesis. The disorder of heme metabolism,  porphyria definition, classification, diagnosis, and treatments discussed elsewhere and a link for the page is provided below. You can also review the practice question by clicking the link provided below Page Links  Heme Biosynthesis and Regulation  Disorders of Heme Biosynthesis & Porphyria Multiple Choice Question in Heme Metabolism and Porphyria Biological Importance of Heme  - Oxygen transport (Hemoglobin) & Storage  (Myoglobin) - Electron carrier in Electron Transport Chain  (Cytochromes) - Prosthetic group of various enzyme - Deficiency of the enzyme causes porphyrias Next Page >> Biosynthetic Pathway for the Synthesis of Heme