FMR Biochemistry: Chapters and session learning objectives (SLOs)

1. Glycolysis
   • SLO 1. Describe the digestion and absorption of common dietary carbohydrates.
   • SLO 2. Explain how glucose is transported into and out of cells by GLUT transporters including the importance of the transporters’ relative affinities.
   • SLO 3. Explain the significance of pancreas and liver producing both hexokinase and glucokinase enzyme isoforms, and why their properties are important for these organs to regulate blood glucose levels.
   • SLO 4. Describe the 3 critical steps of glycolysis that are regulated and explain the significance of these three steps being regulated.
   • SLO 5. Explain how cells cope with the lack of oxygen and inability of pyruvate (end product of glycolysis) to enter the TCA cycle and how the process of anaerobic glycolysis continues.

2. TCA Cycle
   • SLO 1. Explain the significance of the TCA cycle and its biological roles, including its role in catabolic and anabolic pathways.
   • SLO 2. Explain how the irreversible reaction catalyzed by the pyruvate dehydrogenase complex leads to the entry of acetyl-CoA into the TCA cycle and why acetyl-CoA cannot be used as a substrate for gluconeogenesis
   • SLO 3. Outline the co-factor requirements for the pyruvate dehydrogenase and alpha ketoglutarate dehydrogenase enzymes and the biological consequences of thiamine deficiency.
   • SLO 4. Explain how the TCA cycle is regulated, including which critical steps are regulated.
   • SLO 5. Explain how the TCA cycle can be used for synthesis of intermediates involved in biosynthetic reactions, and how pyruvate carboxylase replenishes oxaloacetate for TCA cycle activity.

3. The Electron Transport Chain and Pentose Phosphate Pathway
   • SLO 1. Outline the process by which ATP is produced as a result of electron flow through the protein complexes of the Electron Transport Chain (ETC).
   • SLO 2. Explain how uncoupler proteins and carbon monoxide (CO) and cyanide (CN) disrupt the ETC.
   • SLO 3. Explain the significance of the pentose phosphate pathway and the different roles served by the irreversible reactions of its oxidative phase and the reversible reactions of its non-oxidative phase.
   • SLO 4. Outline how the oxidative and non-oxidate phases of the pentose phosphate pathway can can be used to either make more NADPH or more ribose-5-phosphate, and what these products are needed for.
   • SLO 5. Understand why red blood cells need the pentose phosphate pathway to detoxify reactive oxygen species (ROS), and explain how glucose 6-phosphate dehydrogenase works in concert with glutathione peroxidase and glutathione reductase to detoxify ROS, such as hydrogen peroxide (H2O2).
   • SLO 6. Determine the consequences of glucose-6-phosphate dehydrogenase deficiency and explain why it is prevalent in regions where malaria is endemic.

5. Gluconeogenesis and Glycogen Metabolism

• • SLO 1. Understand the role of gluconeogenesis and glycogen breakdown in maintaining glucose homeostasis, including the role of glucose-6-phosphatase in the liver.
  • SLO 2. Outline the 3 bypass reactions of gluconeogenesis that differentiate it from glycolysis.
  • SLO 3 .Explain the significance of acetyl-coA not being a substrate for gluconeogenesis.
  • SLO 4. Diagram the mechanisms by which glycogen synthesis and glycogen breakdown are reciprocally regulated.
  • SLO 5. Correlate clinical presentations of Von Gierke disorder (Glucose 6-phosphatase deficiency) with the biochemical and physiological basis.

6. Metabolism of Fructose, Sorbitol, Galactose and Ethanol
   • SLO 1. Explain the functional consequences of fructose, lactose, galactose, sugar alcohols and ethanol metabolism.

7. Introduction to Diabetes
   • SLO 1. Apply biochemical principles underlying hyperglycemia to clinical tests and physiological consequences in diabetes mellitus.
   • SLO 2. Differentiate between T1 and T2DM in terms of origin, mechanisms of pathology, and treatment options.
   • SLO 3. Explain how signaling transduction is related to T1 and T2D.

8. Cholesterol and Lipid Digestion and Trafficking
   • SLO 1. Outline the pathways of lipid transport in the body, including the roles of chylomicrons, VLDL, LDL, and HDL.
   • SLO 2. Outline pathways of dietary cholesterol uptake and transport.
   • SLO 3. Understand the possible mechanisms of familial hypertriglyceridemia.
   • SLO 4. Understand the biological basis of familial hypercholesterolemia.
   • SLO 5. Outline the major pathway of de novo sterol synthesis. Understand the biochemical basis of statin action.

9. Lipid Metabolism, Ketone Bodies and Arachidonic Acid and Eicosanoids
   • SLO 1. Analyze the oxidation of fatty acids, including regulation, the carnitine shuttle and generation of ATP.
   • SLO 2. Diagram the pathways for fatty acid storage and release from adipose tissue and their regulation, highlighting the impact of insulin and counterregulatory hormones.
   • SLO 3. Outline the pathway and regulation of de novo lipid biosynthesis
   • SLO 4. Explain how and why ketone bodies are formed and how they are utilized.
   • SLO 5. Understand the biochemical mechanism behind examples of lipid metabolism dysfunction, including carnitine deficiency and medium chain fatty acyl CoA deficiency.
   • SLO 6. Compare the significance of arachidonate derivatives (COX inhibition by aspirin, prostaglandins, leukotrienes).
   • SLO 7. Recognize the roles of eicosanoids in diverse physiological processes and their roles as inflammatory mediators.

10. Fasting and Postprandial State

• • SLO 1. Explain how CHO and lipid metabolism change during acute and prolonged fasting.
  • SLO 2. Explain how CHO and lipid metabolism change after a meal, focus on metabolism in liver, muscle, brain and adipose tissue.
  • SLO 3. Summarize the actions of insulin, glucagon, and epinephrine in regulating CHO and lipid metabolism.
  • SLO 4. Demonstrate the connections between CHO and lipid metabolism, including how CHO carbon molecules become lipids and vice versa.

11. Proteasome and Lysosome
    • SLO 1. Understand the role of protein turnover in generating amino acids, in protein quality control, and in regulating the abundance of proteins.
    • SLO 2. Delineate the two major pathways of protein turnover: the ubiquitin-proteasome pathway and the lysosomal/autophagosome pathway.
    • SLO 3. Outline the genetic basis and pathophysiology of major lysosomal storage diseases.

12. Nitrogen Metabolism
    • SLO 1. Define the concept of nitrogen balance and explain the role of protein degradation in normal nutrition and disease states.
    • SLO 2. Describe the metabolism of nitrogen using aminotransferases, glutamate dehydrogenase, glutamine synthetase and glutaminase.
    • SLO 3. Describe the significance of the urea cycle in removing nitrogen and the presentation of hyperammonemia with defects in urea cycle enzymes.
    • SLO 4. Discuss the diagnostic significance of aspartate aminotransferase and alanine aminotransferase (AST, ALT).

13. Amino Acid Derivatives
    • SLO 1. Describe the biosynthetic origin and basic function of the biological mediators histamine, gamma-aminobutyric acid (GABA), serotonin and nitric oxide.
    • SLO 2. Describe the biosynthetic origin and basic function of molecules derived from tyrosine: thyroid hormone, melanin, and the catecholamines dopamine, norepinephrine, and epinephrine.
    • SLO 3. Discuss the biosynthetic relationship between creatine and creatine phosphate and the use of creatinine as a clinical analyte.
    • SLO 4. Describe the biochemical role of reduced and oxidized glutathione.

14. Amino Acid, Heme and Bilirubin Disorders
    • SLO 1. Discuss the enzymatic defects in, and clinical consequences of, phenylketonuria (PKU) and homocystinuria.
    • SLO 2. Relate the disruption of the heme biosynthetic pathway to porphyrias and lead poisoning.
    • SLO 3. Describe the importance of heme degradation in the development of hyperbilirubinemia.

15. Single Carbon Metabolism
    • SLO 1. Identify the functions of vitamin B12, and explain the role of intrinsic factor in its absorption.
    • SLO 2. Explain the causes and consequences of Intrinsic Factor, B12 and folate deficiencies.
    • SLO 3. Outline the S-adenosylmethionine and folate cycles and explain why B12 deficiency leads to megaloblastic anemia due to a secondary folate deficiency.
    • SLO 4. Illustrate therapeutic uses of pharmaceuticals that disrupt folate metabolism and describe the consequences

16. Purine and Pyrimidine Metabolism
    • SLO 1. Identify the key points pertaining to the de novo purine and pyrimidine biosynthesis pathways, emphasizing input metabolites, key regulated steps, and significance for physiology and metabolism.
    • SLO 2. Examine the formation of deoxyribonucleotides and the balancing of nucleotide pools.
    • SLO 3. Summarize the key aspects of thymidine biosynthesis and describe the mechanism by which inhibitors of this pathway act in cancer chemotherapy.
    • SLO 4. Analyze the catabolism of nucleotides and the purine salvage pathway, focusing on its role in the pathophysiology of gout.