VL 7 (Katja Arndt) Flashcards
Amino Acid catabolism (in mammals)
- Amino acids are obtained from diet - when proteins are digested
- In the cell, proteins are degraded to amino acids (once broken down, all proteins are treated the same way dependent on organism energy needs)
- Recycled into new proteins
- Oxidized for energy
–> removal of amino group (urea cycle)
–> entry into central metabolism (glykolysis, citrit acid cycle)
Amino acids are not stored, any excess amino acid are degradet
Fates of Nitrogen in organism
Aquatic animals
Nitrogen –> ammonia
* passive diffusion of epithelia cells
* active transport via gills
terrestrial vertebrated & sharks Nitrogen –> urea
* less toxic than ammonia
* high solubility
birds and reptiles
Nitrogen –> uric acid
* rather insoluble
* excretion as paste allows animals to conserve water
Human and great apes produce Urea (from amino acids) and uric acid (from purines)
Nitrogen conversion and degredation takes place in liver –> Kidney
Importance of Amino Acid Metabolism
- for protein biosynthesis
- cells cannot oxidize the amino-group to N2
- Primary degredation product is Ammonia (NH3) –> toxic!!
Solution: Conversion of toxic NH3 into non-toxic, soluble molecule: Urea
liver failure leads to toxic accumulation of ammonia
Name the most important molecules in amino acid metabolism
a-Amino acid (Alanine, Aspartate, Glutamate, Gluatmine)
a-Keto acid (Pyruvate, Oxalacetate, a-Ketogluterate)
How is Ammonia transported in bloodstream?
- ammonia is safely transported as Glutamine
- excess glutamine is processed in the intestine, kidneys and liver
- L-Glutamate
–> glutamine synthase - y-Glutamyl phosphate
–> glutamine synthase - L-Glutamine
–> glutaminase (liver mitochondrial) - Glutamate
Cori and Glucose-Alanine-Cycle
working muscles operate anaerobically and rely on glycolysis for energy
CORI-Cycle
* Glycolysis produces pyruvat –> lactate (regeneration of NAD+ for glycolysis)
* Lactate is transported to the liver, converted to glucose and transported back to the muscle (for energy)
Glucose-Alanine-Cycle
* imortant to eliminate waste nitrogen from amino acid catabolism and replenish energy as glucose
* Pyruvate –> alanine (transported to the liver) –> Glucose (transported back to muscle)
Explain the removal of Nitrogen by Transamination
Transamination = transfer of amino group to other molecule
- Release of free ammonia is toxic
- Ammonia is captured by a series of transaminations
- Transaminations allow transfer of amine to a common metabolite (e.g a-Ketoglutarate) and generate a trafficable amino acid ( e.g: glutamate)
Amino Acid Degredation
Amino Acid Degredation (Step 1):
* Transamination (transfer of amino group to other molecules)
* Deamination (Cleavage of amino group, generation of ammonia, concersion to urea)
1. Oxidative deamination
2. Hydrolytic deamination
3. Eliminating deamination
* Decarbocylation (Cleavage of carbocy group to generate bigenic amins e.g: Histamine, GABA )
Fate of Carbon skeleton amino acids (Step 2)
Explain oxidative Deaminatiom in detail
- Occurs within mitochondrial matrix in liver cells
- Ammonia collected in glutamate is removed by glutamate-dehydrogenase (GDH)
- GDH can use either NAD+ or NADP+ as electron acceptor
- Ammonia –> Urea for excretion
- Pathway for ammonia excretion = transdeamination ( Transamination + Deamination)
positive blood test for GDH indicates liver damage
Explain Hydrolytic Deamination in detail
- Glutamine –> Glutamate
- Asparaginie –> Aspartate
Glutamine – (Glutaminesynthase) -> Glutamate (ATP–> ADP+Pi)
Glutamate – (Glutaminase) -> Glutamine (Pi)
Explain Decarboxylation in detail
Step of amino acid degredation
- Generation of biogenic amines
- Pyridoxalphophate (PLP) as coenzyme
- Almost all amino acids
a-Amino acid – (Amino acid decarboxylase (PLP)) –> biogenic amine (abgabe von CO2)
Name the Nitrogen-acquiring reaction of the urea cycle
(Where does the nitrogen comes from?)
- Ammonia is recaptured via synthesis of carbamoyl phosphate
HCO3- + NH3 + 2 ATP –> Carbamoyl phosphate + ADP + Pi - Second nitrogen comes from aspartate
Explain the fate of carbon skeletons of amino acids
- Intermediates of the central metabolic pathway (glucogenic amino acids)
- Some amino acids result in more than one intermediate
- Ketogenic amino acids can be converted to ketone bodies
Ketogenic amino acids
( aa –> Acetyl-CoA)
- Leu, Ile, Thr, Lys, Phe, Tyr, Trp
Glucogenic amino acids (can be converted to glucose)
- Ala, Cys, Gly, Ser, Thr, Trp (aa –> Pyruvate)
- Arg, Glu, Gln, His, Pro ( aa –> a-Ketoglutarate)
- Ile, Met, Thr, Val ( aa –> succinyl-CoA)
- Phe, Tyr ( aa –> fumarate)
- Asp, Asn (aa –> oxalacetate)
Amino Acid Sythesis (Overview)
- Source of N is Glu or Gln
(Glutamine serves as the primary ammonia donor in amino acid biosynthesis) - Derived from intermediates of:
- Glycolysis
- Citric acid cycle and
- Pentose phosphate pathway
- Bacteria can synthesize al 20 aa
- Mammals require some in diet
—> essential amino acids must be obtained in diet
—> non-essential amino acids are easily made from central metabolites
The 20 common ammino acids are synthesized from the following precursers?
6 precursors
- a-ketoglutarate
- 3-phosphoglycerate
- oxaloacetate
- pyruvate
- phosphoenolpyruvate and erythrose-4-phosphate
- ribose-5-phosphate
several neurotransmitter are derived from amino acids
NO is derived from arginine
6 precursors
Where does amino acid degredation takes place?
