Chapter 17: Amino Acid Metabolism Flashcards
What is nitrogen fixation? What are 3 ways to fix it?
- A process which turns N2 (unusable) into ammonia or nitrate which can be used in organic molecules or organisms
- Biological, industrial, and atmospheric fixation
How is nitrogen cycle maintained?
Nitrogen is fixed -> taken up by plants or bacteria -> recycled as organic material -> eventually denitrified and returned to the atmosphere
How is ammonia incorporated into biomolecules?
- NH4 is incorperated into Glutamate and Glutamine reffered to as ammonia assimilation. This process is mediated by 3 enzymes
Know the structures, enzymes, coenzymes involved in biosynthesis involving ammonia.
- Two steps
- Requires ATP hydrolysis (γ-glutamyl phosphate intermediate)
- NH4+ replaces phasphate group to make Gln
Why is glutamine synthesis important?
- Glutamine synthesis is main entry point for NH4+ into biomolecules
- Important process for animal cells to be able to transport NH4+ from peripheral tissue to liver in form of Urea
What does Glutamate dehydrogenase do?
α-Ketoglutarate + NH4+ <—(Gln DH)—>Glutamate
- Works in reverse for animals to make NH4+ for carbamoyl phasphate synthesis
How is Glutamine synthetase regulated?
Allosteric (feedback inhibition)
- Glutamine can be used to form many products which then inhibit glutamine
formation
- Alanine, Serine, Glycine
Covalent modification (Adenylylation)
- Adenylylation of Tyr inhibits enzyme activity
- Adenylylation and de- of glutamine synthetase are mediated by enzyme glutamine synthetase adenylyltransferase
What are aminotransferases (Transaminases)?
- Enzymes that allow for the formation of amino acids
What are the cofactors involved and what is the role of aminotransferases?
- PLP (pyridoxal phosphate) acts as an intermediate carrier of amino groups at the active site of aminotransferases
- PMP (pyridoxamine phosphate) can donate its amino group to a-keto acid
Describe the ping-pong enzymatic reaction and how aminotransferases are involved.
- Amino acid binds to active site
- Donates amino group to PLP converting it to PMP(pyridoxamine phosphate) and departs as a-keto acid
- a-ketoglutarate binds and accepts amino group from PMP and departs as aa
(Substrate enters, product leaves, second substrate enters)
Why are digestive enzymes secreted as zymogens?
- To ensure enzymes are not active when they shouldn’t be. Otherwise self digestion may occur.
What are two ways intracellular proteins are degraded to amino acids in animals?
ATP independent:
- Occurs in lysosomes
- Non-selective degradation
ATP dependent:
- Occurs in proteasome
- Selective - ubiquinated proteins
How is the amino group removed from amino acids?
- Amino acids that accumulate can either be recycled for protein synthesis or be deaminated
- Deamination generates NH4+ to be used in biosynth or excreted as urea
How is excess nitrogen excreted by animals? How do humans do it?
- Plants conserve almost all the nitrogen
- Aquatic vertebrates release ammonia into their environment
- Many terrestrial vertebrates and sharks excrete nitrogen as Urea (less toxic more soluble)
- Birds, reptiles excrete uric acid
- Humans and great apes excrete nitrogen as Urea (amino acids) and uric acid (purines)
What is the Glucose-Alanine cycle? How does it help ammonia transportation from muscle to liver?
- A cycle which removes N from Ala to make pyruvate and glutamate
- Pyruvate produces glucose via gluconeogenesis then glucose which is sent to muscle to be used or forms glycogen
- Deamination of Glu by glutamate dehydrogenase in liver generates NH4+ used to make urea for nitrogen excretion
What are the 5 steps in the Urea cycle? Where do they take place? What enzymes are involved? (No structures needed)
- NH4+ + HCO3- + 2ATP —(carbamoyl phosphate synthetase I)—> Carbamoyl phosphate + 2 ADP
- Carbamoyl phosphate + Ornithine —(Ornithine transcarbamoylase)—> Pi + Citrulline EXITS MITO MATRIX
- Citrulline + Aspartate + ATP —(Argininosuccinate synthetase)—> Argininosuccinate + AMP + PPi
- Argininosuccinate —(Argininosuccinase)—> Fumarate + Arginine
- Arginine + H2O —(Arginase)—> Urea + Ornithine ENTERS MITO MATRIX
What is the role of the aspartate-arginiosuccinate shunt in Urea cycle? How does it lower the energy cost in Urea cycle?
- The role is to help synthesized arginosuccinate
- It lowers the cost by transporting Aspartate from the mitochondrial matrix to the cytosol so that less ATP is required to make Arginosuccinate
How is the Urea cycle regulated?
- High levels of Glutamate and acetyl-CoA in liver lead to synthesis of N-acetylglutamate
- Arginine is an allosteric promoter of N-acetylglutamate synthase
- Carbamoyl phosphate synthetase I activity is stimulated by N-acetylglutamate
Why are genetic defects in Urea cycle life threatening? What treatment is there for argininosuccinase deficiency?
- Complete loss of Urea cycle causes death shortly after birth
- Deficiency in urea cycle emzymes results in hyperammonemia (elevated NH3 levels in blood)
- Need to restrict dietary protein to limit N intake
L-arginine
- Argininosuccinate is excreted in urine because it is soluble
- High amounts of L-arginine are ingested to maintain Ornithine flux
Which amino acids are essential? Which aren’t?
Essential: R, H, I, L, K, M, F, T, W, V
Non essential: A, N, D, C, E, Q, G, P, S, Y
What are glucogenic and ketogenic amino acids? Which amino acids are keto/glucogenic?
Gluconeogenic:
- Can be converted to precursors used in gluconeogenesis
- A,C,D,E,G,H,M,N,P,Q,R,S,V
Ketogenic:
- Can be converted to acetyl-CoA
- K, L
Both:
W, I, F, T, Y
Which cofactors are involved in amino acid catabolism?
PLP (-NH2)
Tetrahydrobiopterin (-OH groups)
1C transfers:
Biotin (CO2)
Tetrahydrofolate (-CH3,Ch2OH, CHO)
S-Adenosylmethionine (NH3)
Which enzymes are deficient in the genetic disorders Alkaptonuria and PKU affecting amino acid catabolism?
Alkaptonuria:
- Mutation of Homogentisate-1,2-dioxygenase
Phenylketonuria:
- Deficiency in phenylalanine hydroxylase
What is the source of N for amino acid biosynthesis?
- The source of N is Glu or Gln
- Obtained in diet by humans
Where does a-ketoglutarate come from and what amino acids can it form?
- Comes from Citrate cycle
- Glutamate
- Glutamine
- Proline
- Arginine
Where does 3-Phosphoglycerate come from and what amino acids can it form?
- Comes from glycolysis
- Serine
- Glycine
- Cysteine
Where does Oxaloacetate come from and what amino acids can it form?
- Comes from Citrate cycle
- Aspartate
- Asparagine
- Methionine*
- Threonine*
- Lysine*
(* indicates it is essential in humans)
Where does pyruvate come from and what amino acids can it form?
- Comes from glycolysis
- Alanine
- Valine*
- Leucine*
- Isoleucine *
(* indicates it is essential in humans)
Where does phosphoenolpyruvate (& erythrose 4-P)come from and what amino acids can it form?
- Comes from glycolysis
- Tryptophan*
- phenylalanine*
- Tyrosine (derived from Phe)
(* indicates it is essential in humans)
Where does RIbose 5-P come from and what amino acid can it form?
- Comes from Glucose-6-P
- Histidine*
(* indicates it is essential in humans)
What causes jaundice? How is it treated in newborns?
- Caused by blocked bile secretion which causes bilirubin to leak from the liver into the blood
- Causes yellowing
- Newborns are treated with fluorescent lamp causes a photochemical conversion to a more soluble and excretable compound
Which amino acids are precursors for Glutathione? What is the cellular role for glutathione?
- Glutamate, cysteine, and glycine
- Acts as a redox buffer
- Helps rid the body of harmful oxygen radicals
Which amino acid is the precursor for catecholamines (Dope, norep, epin) and melanins?
- Tyrosine
Enzymes: Tyrosine hydroxylase, armonatic amino acid decarboxylase (dopamine), dopamine b-hydroxylase (noreipinephrine), Phenylethanolamine N-methyltransferase (epinephrine)
Which enzyme deficiency will cause albanism?
