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Overview of Nitrogen Metab
Lecture 55
54
Medical
Graduate
01/09/2009

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Term
aminotransferases (transaminases)
Definition
alpha amino acids --> alpha keto acids
Term

Glutamine Synthetase

(equation)

Definition
glutamate + NH4+ + ATP → glutamine + ADP + Pi + H+
Term

Where is glutamate synthase present?

 

Definition
Plants and bacteria, not present in animals
Term
the equation for glutamate synthase
Definition

a-ketoglutarate + glutamine + NADPH + H+→ 2 glutamate + NADP+

Term
where is glutamate dehydrogenase found
Definition
all organisms
Term
what is the equation for glutamate dehydrogenase
Definition
a-ketoglutarate + NH4+ + NADPH  glutamate + NADP+
Term
how is glutamine synthetase allosterically regulated
Definition
by alanine, glycine, and six end products of glutamine metabolism (AMP, Tryptophan, Carbamoyl phosphate, CTP, Histidine, Glucosamine 6-phosphate)
Term
what is synergistic regulation
Definition
each inhibitor alone produces only partial inhibition, but the effects of multiple inhibitors is greater
Term
adenylation at Tyr397 ______ enzymatic activity of glutamine synthetase
Definition
inhibits
Term
AT + Pii-UMP leads to what?
Definition
deadenylation of Glutamine synthetase and its activation
Term
AT+Pii leads to what?
Definition
adenylation of glutamine synthetase and its inactivation
Term
What two things inhibit Uridyltransferase (UT)
Definition
glutamate and Pi
Term
What two things stimulate UT?
Definition
alpha-ketoglutarate + ATP
Term
Pii and its relations with transcription of the glutamine synthetase gene
Definition
Pii inhibts transcription of glutamine synthetase gene and uridylylated Pii activates it
Term
Transamination reactions are carried out by enzymes containing what?
Definition
Pyridoxal phosphate (PLP)...it's aminated form is pyridoxamine phosphate
Term
Transfer of one carbon groups is carried out by which two compounds
Definition
tetrahydrofolate and S-adenosylmethionine as cofactor
Term
transfer of amino groups derived from amide nitrogen of glutamine is carried out by what?
Definition
enzymes known as glutamine amidotransferases
Term
what are the two domains for glutamine amidotransferases
Definition
glutamine binding domain (with Cys in the active center), NH3 acceptor domain
Term

The g-amido nitrogen of glutamine (red) is released as NH3 in a reaction that involves a covalent _____________

Definition
glutamyl enzyme intermediate
Term
Glutaminase
Definition
acts in a similar way to glutamine amidotransferase, but uses H2O as the second substrate yeilding NH4+ and glutamate
Term
Ribose-5 phosphate (from the pentose phosphate pathway) + ATP -->
Definition
5-phosphorybosil-1-pyrophosphate (PRPP) + AMP
Term
the formation of PRPP is catalyzed by what enzyme?
Definition
ribose phosphate pyrophosphokinase
Term
alpha-Ketoglutarate gives rise to what four things?
Definition
glutamate -->glutamine, proline, arginine
Term
arginine is made directly from glutamate in...?
Definition
bacteria
Term
important steps in the biosynthesis of arginine from glutamate in bacteria
Definition

eventually ornithine is formed

 

Ornithine-->L-Citrulline-->Argininosuccinate-->Arginine

Term
ornithine d-aminotransferase
Definition

converts Glutamate y-semialdehyde to Ornithine and vice versa

 

 When arginine form diet or protein turnover is insufficient for protein synthesis, it operates in the direction of ornithine formation, which is then converted to citrulline and arginine in the urea cycle   

Term
What amino acids are derived form 3-phosphoglycerate
Definition
3-phosphoglycerate ->Serine-->Glycine and Cysteine
Term

Glycine Synthase

(Glycine Cleavage Enzyme)

Definition

In the liver of vertebrates, glycine is also made

from CO2 and NH4+
Term
To generate cysteine ______ furnishes the sulfur atom and ________ supplies the carbon skeleton
Definition
Methionine furnishes the sulfur artom and serine supplies the carbon skeleton
Term
What is synthesiszed from methionine in mammals
Definition
Homocysteine
Term
What two compounds are used to help make homocysteine from methionine?
Definition
S-adenosylmethionine, and S-adenosylhomocysteine
Term
pyruvate + glutamate
Definition
a-ketoglutarate + alanine
Term
oxaloacetate + glutamate
Definition
a-ketoglutarate + aspartate
Term

asparagine synthetase 

Definition
aspartate + glutamine asparagine + glutamate
Term
Oxaloacecetate-->Aspartate--> (4 amino acids)
Definition
Asparagine (N), Methionine (M), Lysine (K), Threonine (T) (precursor of isoleucine)
Term
Pyruvate --> (4 amino acids)
Definition
Alanine (A), Valine (V), Leucine (L), Isoleucine (I)
Term
Chorismate is a key common intermediate in biosynthesis of what 3 amino acids?
Definition
tryptophan, tyrosine, and phenylalanine
Term
Carbon atoms in the benzene ring of Chorismate can be traced to both ____ and _____
Definition
Term
Biosyntheis of tryptophan
Definition

*PRPP (pink) condenses with antranilate and provide

two carbon atoms for indole ring of tryptophan

 

tryptophan synthase has a2b2 subunit structure

 

[image]

Term
What are the three precursors from which Histidine is derived in bacteria and plants
Definition

PRPP contributes five carbons

 

ATP contributes a nitrogen and a carbon

 

glutamine supplies the second ring nitrogen

 

 

(AICAR) is a remnant of ATP:

  it is released at a later stage

 

 

Term
which amino acid is a precursor of porphyrins
Definition
glycine
Term
What is creatine synthesized from?
Definition

Creatine is synthesized from glycine and arginine,

methionine in the form of S-adenosylmethionine,

acts as a methyl group donor

Term
Glutathione (GSH) is made from what 3 amino acids?
Definition
Glutamate, cysteine, and glycine
Term
What is Glutathione (GSH) used for
Definition

serves as a redox buffer, maintaining

sulfhydryl groups of proteins

in the reduced state,

the iron of heme

in the ferrous (Fe2+) state

and reducing glutaredoxin

in deoxyribonucleotide synthesis

Its redox function is also used

to remove toxic peroxides:

Term
Tyrosine gives rise to what neurotransmitters
Definition
Catecholamines (dopamine, norepinephrine, and epinephrine)
Term
Glutamate is decarboxylated into what neurotransmitter?
Definition

g-aminobutyrate (GABA), an inhibitory neurotransmitter

 

underproduction of this is associated with epileptic seizures

Term
Tryptophan is converted into what neurotransmitter?
Definition
Serotonin
Term
Parkinson's disease is associated with what?
Definition

Underproduction of dopamine and is treated with administering of L-dopa

 

 

 

Term
Histidine is decarboxylated to what?
Definition
Histamine, by histidine decarboxylase
Term

Tagamet

(cimethidine)

Definition
  • a structural analog of histamine
  • a prominent example of histamine receptor antagonist
  • promotes the healting of duodenal ulcers by inhibiting secretion of gastic acid
Term
Nitric Oxide (NO) is biosynthesized from what amino acid and how?
Definition

Both steps in biosynthesis of NO from arginine are catalyzed by nitric oxide synthase

                              

The enzyme is activated by interaction with Ca2+ - calmodulin

                  

Nitric oxide synthase enzyme is related to NADPH cytochrome P-450 reductase

Term

Polyamines spermine and spermidine are derived from what two amino acids?

 

What are the steps  in the biosynthesis of these polyamines

Definition
Methionine and Ornithine
 

The first step of the pathway is decarboxylation of ornithine, a precursor of arginine, by a PLP-requiring enzyme ornithine decarboxylase

 

This enzyme is a target of several powerful pharmaceutical inhibitors

 
Term

What enzyme is targeted in treating African Sleeping Sickness?

 

What medication is used?

Definition

The goal is targeting ornithine decarboxylase, which undergoes a rapid turnover in mammalian,but is stable in protist cells.

 

Difluoromethylomithine (DFMO) - the inhibitor provides an alternative electron sink in the form of two fluorine atoms

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