Download Lecture content: How do amino acids differ from carbohydrates and

The catabolism of amino acids and
the urea cycle.
Aminohappojen katabolia
ja ureasykli.
Aminosyrornas kataboli och
ureacykeln.
Lehninger 5ed
Ch18
(Ch18.3 Pathways of amino acid degradation)
Ch22
(Ch22.1 Overview of nitrogen metabolism)
(Ch22.2 Biosynthesis of amino acids)
(Ch22.4 Biosynthesis and degradation of nucleotides)
Ove Eriksson
BLL/Biokemia
[email protected]
Lecture content:
How do amino acids differ
from carbohydrates and fat?
• The route of nitrogen in our organism
• There is no storage form of amino acids
in the human.
• The urea cycle
• Amino acids contain nitrogen.
• Metabolic profiles of tissues
The nitrogen cycle
HUMAN
• Ammonia is toxic to the central
nervous system.
From azotobacter to human
The gastrointestinal
channel
The destiny of ingested
proteins
Stomach:
-pepsin
Pancreas:
-trypsin
-chymotrypsin
-carboxypeptidase
The destiny of
ingested proteins
Amino acids can undergo
oxidative degradation.
About 18% of her body
weight is protein.
1. During normal synthesis and degradation of
cellular proteins.
Muscle proteins are actively
metabolized.
2. When intake of protein exceeds the body’s
need.
3. During starvation and diabetes mellitus.
Degradation of intracellular proteins
by autophagy (=eating itself) or the
proteasome.
General layout of the amino acid
catabolism
General layout of the amino acid
catabolism
General layout of the amino acid
catabolism
1. How is the NH3-group separated
from the carbon ”skeleton” of the
amino acid?
2. How is ammonia converted to
urea?
3. What happens with the carbon
”skeleton”?
- amino acid – -keto acid
NH2
- amino acid – -keto acid
O
O
O
O
O
NH2
O
O
Pyruvate
O
O
Aspartic acid
- amino acid – -keto acid
O
O
O
O
Alanine
O
Oxaloacetic acid
- amino acid – -keto acid
O
O
HS
O
NH2
NH2
O
O
O
O
O
Glutamic acid
O
ketoglutaric acid
HS
O
O
O
O
Cysteine
O
Mercaptopyruvate
- amino acid – -keto acid
HO
Transamination reactions
HO
NH2
O
O
O
Tyrosine
O
O
Hydroxyphenylpyruvate
Amino groups are transferred to -ketoglutarate.
Free ammonia is formed by
deamination of glutamate
dehydrogenase
Transamination
-transaminases
Deaminationglutamate
dehydregenase
Transaminases are used in the
diagnosis of tissue damage
The cell membrane is destroyed in many diseases.
Cytoplasmic enzymes -> leak -> blood stream
Increased concentrations of transaminases
is used for the diagnosis of:
-myocardial infaction
-toxic liver damage
-muscle diseases
General layout of amino acid
catabolism
1. How is the NH3-group separated
from the carbon ”skeleton” of the
amino acid?
Glutamine, alanine and glutamic acid
play a central role in amino acid
metabolism.
2. How is ammonia converted to
urea?
3. What happens with the carbon
”skeleton”?
Transport of amino groups
from periferal tissues
to the liver by glutamine.
General layout of the amino acid
catabolism
In muscle
In liver
Ammonia excreted in different
forms in different organisms.
Ammonia is metabolized to
urea in liver and kidney.
Ammonia is toxic to the CNS.
Ammonia is toxic to the CNS.
Hepatic encephalopathy:
-due to accumulation of ammonia and
other toxic compounds.
Depletion of Krebs cycle
intermediates and decreased
oxidative phosphorylation.
Alcoholic liver disease
Alcoholic liver disease
1
Risk factors: intake of ethanol
men > 60 g/day
women > 40 g/day
for > 10 years
1. Normal liver; extremely smooth
2. Cirrhosis; liver distorted and
shrunken, large nodules of
cell death
3. End stage liver; intense bile
pigmentation, connective
tissue bands
2
3
Symtoms: in the beginning - no symtoms
later - fatigue, icterus, ascites
end stage - hepatic encephalopathy
Urea is produced in the urea cycle.
Carbamoyl phosphate synthetase
Most common protein in liver and kidney mitochondria
Synthesis of carbamoyl phosphate requires ATP.
Urea is produced in the urea cycle
Addition of the 1st amino group
Urea is produced in the urea cycle
Addition of the 2nd amino group
Urea is produced in the urea cycle
Removal of fumarate
Urea is produced in the urea cycle
General layout of the amino acid
catabolism
Formation of urea
General layout of amino acid
catabolism
1. How is the NH3-group separated
from the carbon ”skeleton” of the
amino acid?
2. How is ammonia converted to
urea?
3. What happens with the carbon
”skeleton”?
Glucogenic and ketogenic amino acids
The glucose-alanine
cycle (compare with
Cori cycle):
The human can synthesize some
but not all amino acids from
TCA-cycle intermediates.
Transfer of amino groups
from periferal tissues to
the liver by alanine.
Amino acids are precursors
for the synthesis of a large
number of biologically
important compounds.
Metabolism of
erythrocytes
Overview over the main
metabolic pathways of various
cells and tissues.
tissues.
For clarity the amino acid metabolism has been excluded
Metabolism of neural cells
Metabolism of muscle cells
(myocytes)
Metabolism of white fat cells
(adipocytes)
Metabolism of brown fat
cells
Metabolism of liver cells (hepatocytes)
hepatocytes)
The liver has a central position in the energy metabolism.
Plenty of nutrients?
Starvation?
Recently detected in
adult humans
Uncoupling protein, also
called thermogenin.
Metabolism of liver cells
(hepatocytes)
Plenty of nutrients
Modification
of enzymes in the
well fed state
Metabolism of liver cells
(hepatocytes)
Plenty of nutrients
Induction of
enzymes in the
well fed state
Metabolism of liver cells
(hepatocytes)
Metabolism of liver cells
(hepatocytes)
Starvation
Starvation
Modification
of enzymes during
starvation
Metabolism of betabeta-cell
Induction of
enzymes during
starvation
Metabolism of the betabetacell
• Very catabolic cell.
• Glucose and amino acids are
oxidized in the TCA-cycle.
• Does not have lactate
dehydrogenase.
Glucose (fuel) sensing
sensing by
the betabeta-cell
How does the betabeta-cell fuel
sensor work?
THE END