Download Medical Biochemistry: Course content 2016/2017

Dept of Medical Biochemistry and Biophysics
Bachelor´s programme in Biomedicine
Medical Biochemistry
2016/2017
Medical Biochemistry: Course content 2016/2017
Reading instructions for the textbook Biochemistry (Ferrier, 6th ed,
2013). Please Note: these instructions can be updated and information
added during the course!
Regulatory strategies
Regulation of enzyme activity. Allosterically regulated enzymes. Feed-back inhibition.
Covalent modification with focus on phosphorylation and dephosphorylation. Proteolytic
activation of zymogenes. Pages: 53-67, 248-249, 443-444
Hormonal signal transduction systems: Glucagon and adrenalin (epinephrine) signal
transduction (cyclicAMP-PKA-system, phosphatidylinositol-IP3/DAG-PKC-system), insulin
signal transduction (IRS, PI-3K, PIP 3 , akt/PKB-system, GLUT4 and phosphatases),
glucocorticoid signal transduction. General knowledge about 7TM-, Tyr-kinase- and nuclear
receptors. Pages: 93-96, 307-314, 134 (Fig. 11.13-calmodulin), 205 (Fig. 17.8), 240D, 241
(Fig. 18.28)
Digestion and absorption
Digestion of carbohydrates, lipids and proteins in the gastrointestinal channel. Function of
gastrin, secretin, GLP and CCK. The localization of digestive enzymes and their function.
Colipase. Zymogen activation. Endo- and exopeptidases, respectively. The importance of the
environment for digestion. Importance of the bile for digestion and absorption. Differences
between bile acids and bile salts, and the two most common primary bile salts. Enterohepatic
circulation. Lactose intolerance. Steatorrhea. General absorption mechanisms and specific
mechanisms for absorption of carbohydrates, amino acids/dipeptides and lipids. Enzyme
mechanism for serine proteases. Pages: 86-89, 173-180, 247-250
Energy metabolism
Free energy and equilibrium. ATP as an energy carrier molecule, structural background.
Pyrophosphatase. Nucleoside diphosphate kinase, creatine kinase. Red/ox-coenzymes: NAD,
NADP and FAD. Catabolism and anabolism. Regulation of metabolic pathways. Energy for
muscle work. Pages: 69-73, 91-96, 131-132 (Fig. 11.9, 11.10), 288 (Fig. 21.19), 296, 379-381
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Carbohydrate metabolism
Structures of carbohydrates. Aldose, ketose, uronic acid. Anomers. Mechanism for
cyclization, ring opening, and formation and hydrolysis of glycosidic bonds. Fischer- and
Haworthprojections, stereo formulas for conformations. Structural formulas for the
monosaccharides glucose, galactose, fructose, ribose and deoxyribose, and for the
disaccharides maltose, isomaltose, lactose and sucrose (the glycosidic bonds are important).
The homoglycans cellulose, starch and glycogen: structure (formulas), ocurrence and
function. Page: 292 (Fig. 22.3), Chap. 7
Glycolysis. The role of glucose transporters (GLUT). The entire reaction sequence with
names, structural formulas for understanding, names of enzymes and coenzymes. ATPconsuming steps, ATP-producing steps = substrate level phosphorylations, redox reactions
(aerobically and anaerobically, respectively). Energy balance for glycolysis. ATP-production
under aerobic and anaerobic conditions, respectively. What is meant by “high energy
compounds” and which ones are generated in glycolysis? How can the glycolysis continue
also under anaerobic conditions? Indicate the enzymatic steps that are important for the
regulation of glycolysis! How is the respective enzyme regulated? Pages: 96-107
Gluconeogenesis. Where in the body does the gluconeogenesis occur? Which are the most
important precursors (substrates) for this process? Those steps that are different from
reversed glycolysis should be known in detail (structural formulas for understanding,
enzymes, coenzymes, substrates and products). Energy consumption for generation of
glucose from lactate. The regulation of gluconeogenesis. Lactate metabolism, the Cori cycle.
Chap. 10
The mitochondrion, citric acid cycle and oxidative phosphorylation. General structure of the
mitochondrion, in particular the structure and function of the inner mitochondrial membrane.
Substrate transport over the inner mitochondrial membrane. Shuttle systems for reduced
coenzymes. The entrance of pyruvate into the citric acid cycle. Oxidative decarboxylation
and carboxylation of pyruvate, respectively (structural formulas for understanding, enzymes,
coenzymes and regulation). The complete series of reaction steps in the citric acid cycle with
names, structural formulas for understanding, enzymes and participating coenzymes.
Pyruvate and α-ketoglutarate dehydrogenases (general structure, coenzymes and their
functions). Energy yield in the citric acid cycle. Regulation, rate limiting steps. Connections
between the citric acid cycle and glycolysis. The structure of the electron transport chain.
What type of compounds form the redox couples? The principle for the internal order of
redox couples. Reoxidation of NADH and FADH2. The function of the enzyme complexes.
Mobile carriers. Oxidative phosphorylation, the structure and regulation of ATP-synthase.
Pages: 73-82, Chap. 9
Glycogen. Which enzymes participate in glycogenesis and what are their functions? How is
the activation of glucose carried out? What is a glycogen primer and glycogenin, and what is
the function of this protein? Which enzymes are required for glycogenolysis and how is this
process carried through? How is the metabolism of glycogen regulated via hormones and
allosteric effects, and how does the regulation differ between different organs? In which
organs/tissues is glycogen stored and what is the metabolic role of glycogen in the different
organs/tissues? Chap. 11
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The HMP shunt. Names and structural understanding through to ribose-5-phosphate.
NADPH-producing steps, regulation. The most important functions of the HMP shunt.
Chap. 13
Lipid metabolism Chap. 16-18 (generally)
Lipid structure. Structural formulas for the following lipids: Oleic acid, palmitic acid, stearic
acid, linoleic acid, linolenic acid, arachidonic acid. Mono-, di-, tri-acylglycerols.
Stereospecific numbering. Phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, lysophosphatidylcholine. Cholesterol
including the numbering of carbon atoms. Cholic acid. The concept omega fatty acids and
structures for the omega-3 fatty acids EPA and DHA.
Lipid synthesis, obesity. What is lipogenesis and when does this process occur? What is the
significance of this process in the human body? Which enzyme systems are required for de
novo synthesis of fatty acids? How is the synthesis of fatty acids carried out in the human
body (structural formulas and principle), and what is the subcellular location? What fatty acid
is primarily generated? What coenzymes are needed, and for NADPH, where is it formed
(process)? Extension and introduction of double bonds in fatty acids, subcellular location,
synthesis of arachidonic acid from linoleic acid. The regulation of fatty acid synthesis.
Synthesis of triacylglycerols in liver, adipose tissue and intestine (mucosa). The generation of
glycerol-3-phosphate. Obesity, heredity, BMI. Ob- and Db-genes. Weight reduction methods.
Leptin effects, leptin mutations. Chap. 26 (obesity and leptin)
Phospholipids. De novo synthesis of the phospholipids: phosphatidylcholine,
phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol. Conversion of
phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine, and the direct
transformation of phosphatidylethanolamine to phosphatidylserine and vice versa. Function
of phospholipases A1, A2, C and D. The role of phospholipids in the cell. The structure and
function of phosphatidylglycerol, cardiolipin, sphingolipids and gangliosides (in principle).
Cholesterol. The synthesis of cholesterol from acetyl-CoA to mevalonic acid using structural
formulas. The principle of the continued synthesis to cholesterol. Rate limiting step
(substrate, products, enzyme and coenzyme) and its regulation.
Lipoproteins. Which are the common lipoproteins and how do they differ regarding the lipid
composition? What is their function? Why are the lipids contained in chylomicrons and
VLDL mainly taken up by extrahepatic tissues (primarily adipose and muscle tissues)?
Lipoprotein lipase function and regulation in adipose and muscle tissues, respectively. The
function of apolipoproteins B, C-II and E, and the PCAT (LCAT) enzyme. The importance of
the LDL-receptor. Take up of different lipoproteins (chylomicron ”remnants”, HDL and
LDL). Understand and explain the terms ”the evil and the good cholesterol”. Atherosclerosis,
theories about the development of the disease. Treatment of hypercholesterolemi.
Lipolysis and ketone bodies. Lipolysis and its hormonal regulation. Conditions with increased
lipolysis and causes to this. Transport of free fatty acids in plasma. Why is the liver taking up
a great deal of the fatty acids? Where and how is glycerol metabolized? Activation of fatty
acids. Carnitine shuttle. The β-oxidation of fatty acids (formulas). Energy production at
complete oxidation of fatty acids. Differences and similarities between de novo synthesis and
β-oxidation of fatty acids. Metabolism of unsaturated fatty acids. The names and structures of
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ketone bodies. In which organ are they synthesized? At what conditions and why are an
excess of ketone bodies produced, and what are the effects in the body? The biosynthesis of
ketone bodies (formulas) and its subcellular location. In which organs and how are ketone
bodies catabolized? The regulation of ketone body synthesis.
Steroid hormones. The most important steps in the synthesis and inactivation of steroid
hormones and vitamin D, including their structures and nomenclature. Hydroxylation by
cytochrome P450. General function of mineralocorticoids, glucocorticoids, sex hormones and
vitamin D3. Cellular mechanism of action for steroid hormones. Pages: 237-240
Prostaglandins, leukotrienes. Structures, nomenclature and synthesis of prostaglandins,
thromboxanes and leukotrienes. Mechanism of action for aspirin. The most important
biological functions for eicosanoids. Pages: 213-217
Amino acids, one carbon pool
The structure of all common amino acids. General protein- and amino acid metabolism. The
proteasome, ubiquitin. Essential amino acids. Transamination, mechanism and importance,
ASAT (AST) and ALAT (ALT). Oxidative deamination. Synthesis of urea (structural
formulas for understanding, regulation and ATP consumption). Glutamine, importance for
acid-base balance. Glucogenic and ketogenic amino acids – which are entirely ketogenic?
One carbon pool. Methionine and the methylation cycle. Folic acid, THF, one carbon
fragments in the one carbon pool: From which amino acids, what are the one carbon
fragments used for? How can the one carbon pool be manipulated pharmacologically?
Creatine and creatine phosphate. Metabolism of Phe. Synthesis of serotonin and adrenalin
(epinephrine). NO, generation and importance. Pages: 2-3, 150-151, 245-247, 250-259, 285288, 374-377, Chap. 20
Oxidative stress
Redox reactions. Generation and breakdown of oxygen radicals. Systems that protect the cell
against toxic oxygen radicals. Glutathione, structure and role. Glutathione peroxidase,
catalase. The redox systems of the cell. Vitamins E and C. Pages: 377-378, 391
Alcohol, liver and heme
Alcohol metabolism and its regulation. Where in the body and where in the cells do the
reactions take place? Genetic differences regarding alcohol metabolism. Effects of alcohol
and its metabolites on the intermediary metabolism. Hypoglycemia. Other alcohol effects.
Acute effects on the brain. Pharmacological treatment of alcohol dependence. Modern
theories about cirrhos development.
Heme. Synthesis and degradation of heme. Synthesis of ALA from Gly and succinyl-CoA,
synthesis of porphobilinogen. General structure for porphyrinogens and porphyrins.
Generation of biliverdin, bilirubin, its glucuronide. Icterus (jaundice), different types and
their causes. Pages: 277-285
Nucleotides
Structure of purines/pyrimidines, nucleosides, nucleotides. Nomenclature. Formulas for the
bases in RNA and DNA. Origin of the atoms in purines/pyrimidines. The regulation of purine
synthesis. Synthesis and the first step in the use of PRPP. Carbamylphosphate synthetase II.
Salvage pathway for purine nucleotides. Principles for degradation of AMP and GMP,
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xanthine oxidase and the sequence hypoxanthine – xanthine – uric acid. Allopurinol and
treatment of gout. Synthesis of deoxyribonucleotides including dTTP, the importance of the
one carbon pool. Principles for drugs affecting nucleotide biosynthesis. Chap. 22
Inborn errors of metabolism
Subdivision. PKU. Methylmalonic aciduria. Galactosemia. Hereditary fructose intolerance.
Betaoxidation defects. Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency.
Diagnostics and treatments. Pages: 270-272, 194, 141-142, 138-139, 193
Integration of intermediary metabolism, blood glucose
Coordination/interplay between different organs in starvation, stress, nutrient intake, muscle
work and diabetes. Hormone systems, transfer of energy rich substances between organs.
Hormonal blood sugar regulation. Participating hormones and their effects on intermediary
metabolism. From where do the hormones come and at which occasions? How is the glucose
uptake regulated in different tissues? Glucose tolerance and how it is determined. Explain the
late complications in diabetes: sorbitol, glycation and oxidative stress.
Page: 140, Chap. 23-25
Also included in the final examination:
Lab theory
Lipid lab and protein purification lab: Basic principles for the methods used.
Articles
Be able to summarize and use scientific articles to solve biomedical questions/problems.
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