Medical Biochemistry
summary (exam 1+2)
1
,Overview of human metabolism 3
Carbohydrate and glucose management 5
Protein and amino acid metabolism 10
Fat and lipid metabolism 14
Intermediary metabolism 18
Hormonal regulation: Introduction and metabolic hormones 23
Hormonal regulation: Stress hormones 27
Modeling the regulation of enzymes 30
Selected essays partial exam 1 32
Fat, cholesterol & atherosclerosis 34
Histology of the Blood vessels 39
Histology of the Liver 42
Histology of the Kidney 44
Histology of the Respiratory system 47
Anorexia, obesity & diabetes 51
Muscle metabolism and sport 56
Liver detoxi cation & alcohol 60
Micronutrients: superfoods and health 64
Modeling the behavior of systems of enzymes 69
Selected essays partial exam 2 72
2
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, Overview of human metabolism
- Human metabolism includes a metabolic network of 500 essential cellular reactions
- Containing metabolites connected via enzyme-catalyzed reactions
- Regulated by: hormones + metabolite levels (inside cells) + lifestyle
- Carbohydrates:
- Glucose <-> starch (via diet) or glycogen (via body stores)
- Glucose is only carbohydrate that brain can use
- Can be linear or branched due to carbohydrate bonds
- Proteins:
- Protein <-> amino acids
- Protein = amino acids combined via peptide bonds
- Fat/triglycerides:
- Triacylglycerol = glycerol + 3 fatty acids
- Glycolysis is the central pathway in human metabolism
- Metabolic processes are linked
- Occurs in cytosol
- Intermediates of glucose catabolism are building blocks for many anabolic pathways:
other carbohydrates + lipids + amino acids + DNA/RNA
- Intermediates are crucial checkpoints; decide where to go in pathway
- 3 crucial points where metabolism is decided:
1. Glucose 6-phosphate
-> glucose (only generated in liver)
-> glycogen (=stored glucose in liver)
-> pyruvate
-> ribose 5-phosphate -> Pentose Phosphate Pathway
2. Pyruvate
-> gluconeogenesis
-> acetyl CoA
<-> lactate / alanine
3. Acetyl CoA
-> cholesterol / ketone bodies
-> CO2 (via TCA cycle)
<-> FA
- Many metabolic roads to+from acetyl CoA
- Have most intense regulation
- Major fates of fuels in the fed state:
- Glucose -> energy via oxidation + synthesis of many compounds + storage in form of
glycogen/triglycerides
- Amino acids -> energy via oxidation + synthesis of protein and N-containing compounds
- AA cannot be stored -> generate fat or make proteins
- Fats -> energy via oxidation + synthesis of membrane lipids + storage in form of TG
- Fat storage cannot be regulated -> only 1 way: obesity
- Free energy carriers: ATP, GTP, NAD(P)H, FADH
- Building blocks: 12 ‘precursor metabolites’ -> macromolecule+ATP synthesis
- Homeostasis — ATP produced as needed:
- Only limited amount of ADP -> ATP used+generated as needed
- ADP + Pi -> ATP using energy via oxidation of carbohydrate/lipid/protein
- ATP -> ADP + Pi via energy utilization (e.g. biosynthesis/thermogenesis)
- Burning food: oxidation by O2 (via electron transport chain), energy caught as ATP, rest lost as
heat
- Glucose/FA/AA -> acetyl coA -> TCA cycle -> ETC -> ATP
- 2 C of acetyl CoA released as CO2
- H released as H2O
- From acetyl CoA, you cannot generate glucose again; only energy
3
, - Useful energy stored in ATP
- ATP (with high-energy phosphate bonds) -hydrolysis> ADP + Pi
- ATP hydrolysis is exothermic reaction
- Coupling of exotherm and endotherm reactions: in living organisms, energy requiring
processes are endothermic (ΔG>0) -> driven by energy generating processes (exothermic,
ΔG<0), often ATP hydrolysis
- Hydrolysis of ATP needed to be able to run endothermic reactions
- Compartmentalization of metabolic reactions:
- Some reactions take place in cytosol, others in mitochondria
- In mitochondria: generation of ATP (TCA cycle + ETC + ATP synthase) + degradation
of FA via beta oxidation
- In cytosol: synthesis of FA
- Regulation so metabolites don’t enter mitochondria; shuttles important regulators for
tra cking metabolites in cell
- Also many organs have their own tissue metabolism
- Liver = central factory
- Regulation of oxidative phosphorylation and ATPase:
- ATP synthase uses energy from proton gradient (coming from NADH, produced in TCA
cycle) to produce ATP -> when all ADP has been converted to ATP, enzyme stops -> no
regeneration of NAD+ -> accumulation of NADH + cannot proceed through TCA cycle ->
no more energy
- TCA cycle catches energy in small steps by using small packages of energy that are
captured by NADH (NAD+ -> NADH), and then used for ATP synthesis
- Regulation of TCA cycle: without NAD+, the reaction of isocitrate -> α-ketoglutarate (and
thus TCA cycle) cannot proceed
- When oxidative phosphorylation stops recycling NADH, TCA cycle will also stop
- Accumulation of NADH is negative regulator of TCA cycle
- When energy is needed, ADP levels are high and TCA cycle is wanted to proceed
- Exercising -> using lot of ATP = release of calcium by muscles, which speeds up
ATP synthesis
- ATP generation is a self regulating system: under homeostatic conditions, ATP is
constantly being synthesized+used
- You make 60kg ATP from 1500 kcal/day, while only having several grams of ADP
- When there is su cient ATP: TCA cycle stops, and excess acetyl CoA is converted to fat
- Fed state: excess dietary fuel (energy) is stored in fuel stores (fat/glycogen/protein)
- After meal: store energy
- Excess glucose is converted to fat; liver can store max. ~200g glycogen
- Fasting state: release+oxidation from fuel stores (fat/glycogen/protein) to form energy
- Between meals: protein degradation for glucose synthesis for brain + release energy via
mobilization of FA
- During negative nitrogen balance, the body uses AA to feed cells -> body protein
breakdown
- Nitrogen excretion during fasting; urea excretion ~ protein breakdown
- Liver makes glucose for the brain
- Prolonged starvation: ketone bodies (=backup system) are generated from FA
- KB are only backup for brain as fuel, besides glucose
- Prevents breakdown of essential proteins and muscles (e.g. cardiac muscle)
- 2 ketone bodies: acetoacetate + β-hydroxybutyrate
- During rst days, you’re dependent on glucose generated by body; after ~2 days, ketone
bodies start being generated
4
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summary (exam 1+2)
1
,Overview of human metabolism 3
Carbohydrate and glucose management 5
Protein and amino acid metabolism 10
Fat and lipid metabolism 14
Intermediary metabolism 18
Hormonal regulation: Introduction and metabolic hormones 23
Hormonal regulation: Stress hormones 27
Modeling the regulation of enzymes 30
Selected essays partial exam 1 32
Fat, cholesterol & atherosclerosis 34
Histology of the Blood vessels 39
Histology of the Liver 42
Histology of the Kidney 44
Histology of the Respiratory system 47
Anorexia, obesity & diabetes 51
Muscle metabolism and sport 56
Liver detoxi cation & alcohol 60
Micronutrients: superfoods and health 64
Modeling the behavior of systems of enzymes 69
Selected essays partial exam 2 72
2
fi
, Overview of human metabolism
- Human metabolism includes a metabolic network of 500 essential cellular reactions
- Containing metabolites connected via enzyme-catalyzed reactions
- Regulated by: hormones + metabolite levels (inside cells) + lifestyle
- Carbohydrates:
- Glucose <-> starch (via diet) or glycogen (via body stores)
- Glucose is only carbohydrate that brain can use
- Can be linear or branched due to carbohydrate bonds
- Proteins:
- Protein <-> amino acids
- Protein = amino acids combined via peptide bonds
- Fat/triglycerides:
- Triacylglycerol = glycerol + 3 fatty acids
- Glycolysis is the central pathway in human metabolism
- Metabolic processes are linked
- Occurs in cytosol
- Intermediates of glucose catabolism are building blocks for many anabolic pathways:
other carbohydrates + lipids + amino acids + DNA/RNA
- Intermediates are crucial checkpoints; decide where to go in pathway
- 3 crucial points where metabolism is decided:
1. Glucose 6-phosphate
-> glucose (only generated in liver)
-> glycogen (=stored glucose in liver)
-> pyruvate
-> ribose 5-phosphate -> Pentose Phosphate Pathway
2. Pyruvate
-> gluconeogenesis
-> acetyl CoA
<-> lactate / alanine
3. Acetyl CoA
-> cholesterol / ketone bodies
-> CO2 (via TCA cycle)
<-> FA
- Many metabolic roads to+from acetyl CoA
- Have most intense regulation
- Major fates of fuels in the fed state:
- Glucose -> energy via oxidation + synthesis of many compounds + storage in form of
glycogen/triglycerides
- Amino acids -> energy via oxidation + synthesis of protein and N-containing compounds
- AA cannot be stored -> generate fat or make proteins
- Fats -> energy via oxidation + synthesis of membrane lipids + storage in form of TG
- Fat storage cannot be regulated -> only 1 way: obesity
- Free energy carriers: ATP, GTP, NAD(P)H, FADH
- Building blocks: 12 ‘precursor metabolites’ -> macromolecule+ATP synthesis
- Homeostasis — ATP produced as needed:
- Only limited amount of ADP -> ATP used+generated as needed
- ADP + Pi -> ATP using energy via oxidation of carbohydrate/lipid/protein
- ATP -> ADP + Pi via energy utilization (e.g. biosynthesis/thermogenesis)
- Burning food: oxidation by O2 (via electron transport chain), energy caught as ATP, rest lost as
heat
- Glucose/FA/AA -> acetyl coA -> TCA cycle -> ETC -> ATP
- 2 C of acetyl CoA released as CO2
- H released as H2O
- From acetyl CoA, you cannot generate glucose again; only energy
3
, - Useful energy stored in ATP
- ATP (with high-energy phosphate bonds) -hydrolysis> ADP + Pi
- ATP hydrolysis is exothermic reaction
- Coupling of exotherm and endotherm reactions: in living organisms, energy requiring
processes are endothermic (ΔG>0) -> driven by energy generating processes (exothermic,
ΔG<0), often ATP hydrolysis
- Hydrolysis of ATP needed to be able to run endothermic reactions
- Compartmentalization of metabolic reactions:
- Some reactions take place in cytosol, others in mitochondria
- In mitochondria: generation of ATP (TCA cycle + ETC + ATP synthase) + degradation
of FA via beta oxidation
- In cytosol: synthesis of FA
- Regulation so metabolites don’t enter mitochondria; shuttles important regulators for
tra cking metabolites in cell
- Also many organs have their own tissue metabolism
- Liver = central factory
- Regulation of oxidative phosphorylation and ATPase:
- ATP synthase uses energy from proton gradient (coming from NADH, produced in TCA
cycle) to produce ATP -> when all ADP has been converted to ATP, enzyme stops -> no
regeneration of NAD+ -> accumulation of NADH + cannot proceed through TCA cycle ->
no more energy
- TCA cycle catches energy in small steps by using small packages of energy that are
captured by NADH (NAD+ -> NADH), and then used for ATP synthesis
- Regulation of TCA cycle: without NAD+, the reaction of isocitrate -> α-ketoglutarate (and
thus TCA cycle) cannot proceed
- When oxidative phosphorylation stops recycling NADH, TCA cycle will also stop
- Accumulation of NADH is negative regulator of TCA cycle
- When energy is needed, ADP levels are high and TCA cycle is wanted to proceed
- Exercising -> using lot of ATP = release of calcium by muscles, which speeds up
ATP synthesis
- ATP generation is a self regulating system: under homeostatic conditions, ATP is
constantly being synthesized+used
- You make 60kg ATP from 1500 kcal/day, while only having several grams of ADP
- When there is su cient ATP: TCA cycle stops, and excess acetyl CoA is converted to fat
- Fed state: excess dietary fuel (energy) is stored in fuel stores (fat/glycogen/protein)
- After meal: store energy
- Excess glucose is converted to fat; liver can store max. ~200g glycogen
- Fasting state: release+oxidation from fuel stores (fat/glycogen/protein) to form energy
- Between meals: protein degradation for glucose synthesis for brain + release energy via
mobilization of FA
- During negative nitrogen balance, the body uses AA to feed cells -> body protein
breakdown
- Nitrogen excretion during fasting; urea excretion ~ protein breakdown
- Liver makes glucose for the brain
- Prolonged starvation: ketone bodies (=backup system) are generated from FA
- KB are only backup for brain as fuel, besides glucose
- Prevents breakdown of essential proteins and muscles (e.g. cardiac muscle)
- 2 ketone bodies: acetoacetate + β-hydroxybutyrate
- During rst days, you’re dependent on glucose generated by body; after ~2 days, ketone
bodies start being generated
4
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fi ffi
