Medical biochemistry
Lecture 1: overview human metabolism
Metabolism: metabolic network of 500 essential cellular reaction:
- Regulated by:
o Hormones
o Metabolite level
o Lifestyle
Energy sources:
- Carbohydrates:
o One of the most important food sources
o Only energy source ready to be used, containing glucose
- Proteins:
o Composed of multiple amino acids
o Amino acids are an important source to generate glucose whenever the body
runs out of glucose.
- Fat/triglycerides:
o Composed of a glycerol molecule with 3 fatty acids attached
All three are catabolized to enable all to participate in the metabolic pathway in the shape
of acetyl Co-A. During this process oxidation occurs. The energy released is then caught in
the form of ATP. The levels of ATP are kept in homeostasis. ATP is produced as needed, if
not needed it is stored as ADP + Pi.
Glycolysis:
- Central pathway in human metabolism
- Metabolic processes are linked. Intermediates of glucose catabolism are building
blocks for many anabolic pathways:
o Other carbohydrates
o Lipids
o Amino acids
o DNA/RNA
Thermodynamics:
Exothermal (G < 0) endothermal (G > 0)
All energy not caught in the form of ATP is lost in the form of heat, especially for the
exothermic reactions. As endothermic reactions need extra energy for activation, the
coupling of an exo- and endothermic reaction is very efficient. = little loss of energy.
1
,The process from acetyl-coA and TCA cycle occurs in the inner space of the mitochondria. So in the
mitochondria, ATPase occurs as well upon presence of ADP + Pi and passage of H+ across the
membrane. The passage of H+ helps keep the electrochemical potential ready as when ATPase
stops, the proton gradient would build up halt of OXPHOS as NAD+ is not regenerated. As NAD+ is
used for regulation of the TCA cycle, NADH needs to be recycled by OXPHOS
The muscles use a lot of ATP for contraction. Luckily, due to homeostasis, the levels of ATP are
relatively stable at rest and during exercise=.
However, when there is sufficient ATP, the acetyl-coA is converted to FA and then stored as TG.
The conversion pyruvate acetyl-coA is the most important regulator of entry in the TCA cycle. Its
associated enzyme, pyruvate dehydrogenase, is controlled by NAD+. When there is an excess of
pyruvate, it can be transformed in either
- Lactate
- Oxaloacetate
- Ethanol (only in microorganisms)
After a meal, excess glucose is stored, mostly in the liver. However, also the liver has a limit. When
±200 g glucose is present, the overflow is converted to fats via FA synthase. Storage as FA or TG has
no limits.
Between meals, when no new glucose enters the body, energy is released by the liver (and adipose
tissue). When there is no energy to be released, the body will turn to nitrogen to keep the energy
levels for the brain sufficient. This results in the breakdown of body protein. If even that is not
present, e.g. during starvation, ketone bodies (KB) will be produced from FA to prevent degradation
of muscle tissue and transported to the brain only for energy functioning.
Lecture 2: carbohydrate and glucose management
There are different types of sugars: stereoisomers
- Sugars can change confirmation from cyclic to linear and vice versa
- 3D confirmational changes are large: enzymes are often very specific to specific
sugars. So, when the structure changes another enzyme is needed.
Dietary sources of carbohydrates:
- Starch, plants (amylase)
- Dairy (lactose)
- Processed western food (glucose)
Polymers like starch need several enzymes to be degraded. Because carbohydrates are so
important, the degradation starts in the mouth. In the stomach and the pancreas additional
enzymes are released which help breakdown the carbohydrates. The carbohydrates are
degraded to monosaccharides which can be taken up from the food.
Some polymers can’t be degraded as there is no enzymes presents in humans to digest
them. These polymers are called fibers. Bacteria in the gut will use these fibers, and some
are even able to digest them.
2
, Uptake of monosaccharides
- Epithelial cells in the gut have several transporters
o Facilitator transporters: work via diffusion via the concentration gradient. No
ATP needed for this type of transport.
o Active uptake: when glucose levels are very low in the lumen for example.
Now transport should be against the gradient. On top of the epithelial cells
there are glucose transporters.
Lactose intolerance
- Lack of lactase, as lactase won’t be made anymore when humans/animal don’t drink
milk anymore
- Lactose will stay in the intestine, and it will be degraded by bacteria in the intestine.
This releases lactic acid and gas, which causes bloating. The lactic acid will have an
osmotic effect which takes a lot of water into the intestines, leading to diarrhea.
- High prevalence in Asia and Africa
Galactosemia and fructosemia
- Serious diseases, usually in the liver. Because most monosaccharides are degraded in
the liver.
- When there is a lack in enzymes which degrade galactose, there will be an buildup of
intermediate products. Which gives a lot of toxic effects.
Key points
- Carbohydrates are sugars and their polymers: glucose is the most important
monosaccharide. Most high-carb foods contain glucose polymers
- Polysaccharides: need to be digested by glucosidases, amylase most important.
Resulting tri- and disaccharides are hydrolyzed to monosaccharides that are taken up
by epithelial cells in the intestine
- Transport mechanisms: via glucose transporters
- Some sugars are not tolerated
Glycogen
Glycogen: is a form of glucose storage. A very branched structure of glucose molecules in
different number of linkages (so different types of enzymes needed). Glycogen stored in:
- Muscles:
o Function: glycogen is main glucose source during exercise
o Regulation: responsive to insulin (storage) and epinephrine (via PKA) and
activity via Ca2+ (exercise, stress). Does not respond to glucagon!!!
- Liver:
o Function: is glucose storage for blood glucose homeostasis in between meals
or during fasting
o Regulation: responsive to insulin (storage) and glucagon/epinephrin (via PKA)
(fasting, exercise, stress)
3
Lecture 1: overview human metabolism
Metabolism: metabolic network of 500 essential cellular reaction:
- Regulated by:
o Hormones
o Metabolite level
o Lifestyle
Energy sources:
- Carbohydrates:
o One of the most important food sources
o Only energy source ready to be used, containing glucose
- Proteins:
o Composed of multiple amino acids
o Amino acids are an important source to generate glucose whenever the body
runs out of glucose.
- Fat/triglycerides:
o Composed of a glycerol molecule with 3 fatty acids attached
All three are catabolized to enable all to participate in the metabolic pathway in the shape
of acetyl Co-A. During this process oxidation occurs. The energy released is then caught in
the form of ATP. The levels of ATP are kept in homeostasis. ATP is produced as needed, if
not needed it is stored as ADP + Pi.
Glycolysis:
- Central pathway in human metabolism
- Metabolic processes are linked. Intermediates of glucose catabolism are building
blocks for many anabolic pathways:
o Other carbohydrates
o Lipids
o Amino acids
o DNA/RNA
Thermodynamics:
Exothermal (G < 0) endothermal (G > 0)
All energy not caught in the form of ATP is lost in the form of heat, especially for the
exothermic reactions. As endothermic reactions need extra energy for activation, the
coupling of an exo- and endothermic reaction is very efficient. = little loss of energy.
1
,The process from acetyl-coA and TCA cycle occurs in the inner space of the mitochondria. So in the
mitochondria, ATPase occurs as well upon presence of ADP + Pi and passage of H+ across the
membrane. The passage of H+ helps keep the electrochemical potential ready as when ATPase
stops, the proton gradient would build up halt of OXPHOS as NAD+ is not regenerated. As NAD+ is
used for regulation of the TCA cycle, NADH needs to be recycled by OXPHOS
The muscles use a lot of ATP for contraction. Luckily, due to homeostasis, the levels of ATP are
relatively stable at rest and during exercise=.
However, when there is sufficient ATP, the acetyl-coA is converted to FA and then stored as TG.
The conversion pyruvate acetyl-coA is the most important regulator of entry in the TCA cycle. Its
associated enzyme, pyruvate dehydrogenase, is controlled by NAD+. When there is an excess of
pyruvate, it can be transformed in either
- Lactate
- Oxaloacetate
- Ethanol (only in microorganisms)
After a meal, excess glucose is stored, mostly in the liver. However, also the liver has a limit. When
±200 g glucose is present, the overflow is converted to fats via FA synthase. Storage as FA or TG has
no limits.
Between meals, when no new glucose enters the body, energy is released by the liver (and adipose
tissue). When there is no energy to be released, the body will turn to nitrogen to keep the energy
levels for the brain sufficient. This results in the breakdown of body protein. If even that is not
present, e.g. during starvation, ketone bodies (KB) will be produced from FA to prevent degradation
of muscle tissue and transported to the brain only for energy functioning.
Lecture 2: carbohydrate and glucose management
There are different types of sugars: stereoisomers
- Sugars can change confirmation from cyclic to linear and vice versa
- 3D confirmational changes are large: enzymes are often very specific to specific
sugars. So, when the structure changes another enzyme is needed.
Dietary sources of carbohydrates:
- Starch, plants (amylase)
- Dairy (lactose)
- Processed western food (glucose)
Polymers like starch need several enzymes to be degraded. Because carbohydrates are so
important, the degradation starts in the mouth. In the stomach and the pancreas additional
enzymes are released which help breakdown the carbohydrates. The carbohydrates are
degraded to monosaccharides which can be taken up from the food.
Some polymers can’t be degraded as there is no enzymes presents in humans to digest
them. These polymers are called fibers. Bacteria in the gut will use these fibers, and some
are even able to digest them.
2
, Uptake of monosaccharides
- Epithelial cells in the gut have several transporters
o Facilitator transporters: work via diffusion via the concentration gradient. No
ATP needed for this type of transport.
o Active uptake: when glucose levels are very low in the lumen for example.
Now transport should be against the gradient. On top of the epithelial cells
there are glucose transporters.
Lactose intolerance
- Lack of lactase, as lactase won’t be made anymore when humans/animal don’t drink
milk anymore
- Lactose will stay in the intestine, and it will be degraded by bacteria in the intestine.
This releases lactic acid and gas, which causes bloating. The lactic acid will have an
osmotic effect which takes a lot of water into the intestines, leading to diarrhea.
- High prevalence in Asia and Africa
Galactosemia and fructosemia
- Serious diseases, usually in the liver. Because most monosaccharides are degraded in
the liver.
- When there is a lack in enzymes which degrade galactose, there will be an buildup of
intermediate products. Which gives a lot of toxic effects.
Key points
- Carbohydrates are sugars and their polymers: glucose is the most important
monosaccharide. Most high-carb foods contain glucose polymers
- Polysaccharides: need to be digested by glucosidases, amylase most important.
Resulting tri- and disaccharides are hydrolyzed to monosaccharides that are taken up
by epithelial cells in the intestine
- Transport mechanisms: via glucose transporters
- Some sugars are not tolerated
Glycogen
Glycogen: is a form of glucose storage. A very branched structure of glucose molecules in
different number of linkages (so different types of enzymes needed). Glycogen stored in:
- Muscles:
o Function: glycogen is main glucose source during exercise
o Regulation: responsive to insulin (storage) and epinephrine (via PKA) and
activity via Ca2+ (exercise, stress). Does not respond to glucagon!!!
- Liver:
o Function: is glucose storage for blood glucose homeostasis in between meals
or during fasting
o Regulation: responsive to insulin (storage) and glucagon/epinephrin (via PKA)
(fasting, exercise, stress)
3
