Term
|
Definition
- all organisms
- main regulatory enzyme in nitrogen metabolism
- catalyzes:
GLUTAMATE + NH4+ + ATP --> GLUTAMINE + ADP... |
|
|
Term
|
Definition
- plants, bacteria ONLY
- catalyzes:
α-ketoglutarate + NADPH + glutamine + H+ → 2 glutamate + NADP+ |
|
|
Term
| Glutamate Synthesis, alternative pathway |
|
Definition
- minor contributor to glutmate because reverse reaction is more favorable (source of ammonia for urea cycle)
- in all organisms (mito matrix of eukaryotes)
- GLUTAMATE DEHYDROGENASE catalyzes:
α-ketoglutarate + NH4+ + NADPH ↔ glutamate |
|
|
Term
|
Definition
- universal entry point in nitrogen cycle
- incorporated into biomolecules via glutamine and glutamate
|
|
|
Term
| 3 types of regulation for Glutamine Synthetase |
|
Definition
1. allosteric inhibitory regulation (synergistic) 2. covalent modification of Glutamine Synthetase and Adenylyl Transferase 3. transcriptional regulation of gene enocoding glutamine synthetase |
|
|
Term
| Allosteric regulation of glutamine synthetase |
|
Definition
Allosteric inhibition of glutamine synthetase by: - alanine
- glycine
- 6 glutamine metabolic end products
Syngergistic, each inhibitor produces only partial inhibition. Very sensitive and responsive; cell able to nimbly adjust glutamine levels to meet metabolic requirements |
|
|
Term
| Regulation of Glutamine Synthetase by covalent modification |
|
Definition
Adenylylation inhibits enzyme activity of glutamine synthetase. Two methods of adenylylation: - Tyr397 residue
- cascade involving PII, UMP, AT that leads to adenylylation of glutamine synthetase
|
|
|
Term
| Adenylylation Cascade of Glutamine Synthetase |
|
Definition
- in adenylylated form via adenylyltransferase (AT), GS is INACTIVATED
- AT is regulated by binding of PII or PII-UMP complex
- PII is regulated by covalent modification of uridylyltransferase (UT)
AT-PII-UMP = INACTIVE (so less adenylylation of GS; GS actvity is stimulated) AT-PII = ACTIVE (adenylylation stimulated, and GS inactivated) - uridylylation INHIBITED by glutamine and Pi binding to UT
- uridylylation STIMULATED by a-ketoglutarate and ATP binding to PII
|
|
|
Term
| Transcriptional Regulation of Glutamine Synthetase |
|
Definition
- UMP-PII activates transcription of gene encoding glutamine synthetase
- PII decreases transcription of glutamine synthetase gene
|
|
|
Term
|
Definition
- high levels of glutamate maintained in animals via transamination reaction of a-ketoglutarate in amino acid catabolism
- aminotranferases (group of catalyzing enzymes)
- essenital prosthetic group: PLP (pyridoxal phosphate)
a-ketoglutarate --->glutamate via PLP, aminotransferase, donor amino acid
|
|
|
Term
| GLUTAMATE, universal amino donor |
|
Definition
L-glutamate --> a-ketoglutarate via PLP/aminotransferase a-keto acid-->amino acid
- keto acid joins glutamate and receives the amino group donated by the glutamate.
|
|
|
Term
key chemical rearrangements in forming amino acids
|
|
Definition
transamination by enzymes with PLP prosthetic group transfer of one carbon group by tetrahydrofolate (-CHO or -CH2OH oxidation level) or S-adenomethionine (-CH3 oxidation level) transfer of amino group derived from glutamine's amide nitrogen (glutamine amidotransferases, use glutamine as source of amino group)
|
|
|
Term
| Glutamine Amidotransferases: Mechanism |
|
Definition
more than a dozen, but similar mechanism: - 2 domains: (1) glutamine-binding domain, (2) NH3- acceptor (or second substrate) domain
- glutamine binding domain has cys conserved in active site
- glutamyl-enzyme intermediate formed, as NH3 released through a channel to the second domain where it reacts with acceptor
- GLUTAMINASE functions similarly, but H20 is second substrate, yielding NH4+ and glutamate
|
|
|
Term
| Amino acid derivative sources |
|
Definition
GLYCOLYSIS: - 3-phosphoglycerate
- PEP
- pyruvate
CITRIC ACID CYCLE: - Oxaloacetate
- a-ketoglutarate
Pentose Phosphate Pathway (PPP): - erythrose 4-phosphate
- ribose 5-phosphate
|
|
|
Term
GLYCOLYSIS- derived amino acids |
|
Definition
3-Phosphoglycerate PEP + Erythrose 4-Phosphate - trytophan
- tyrosine
- phenylalanine
PYRUVATE - alanine
- valine
- leucine
- isoleucine
|
|
|
Term
CITRIC ACID CYCLE- derived amino acids |
|
Definition
OXALOACETATE - aspartate-->
- asparagine
- methionine
- threonine
- lysine
a-KETOGLUTARATE - glutamate-->
- glutamine
- proline
- arginine
|
|
|
Term
|
Definition
- aspartate-->
- asparagine
- methionine
- threonine
- lysine
|
|
|
Term
|
Definition
- glutamate-->
- glutamine
- proline
- arginine
|
|
|
Term
|
Definition
|
|
Term
PEP + Erythrose 4-Phosphate |
|
Definition
- trytophan
- tyrosine
- phenylalanine
|
|
|
Term
|
Definition
- alanine
- valine
- leucine
- isoleucine
|
|
|
Term
|
Definition
|
|
Term
|
Definition
- isoleucine (I)
- leucine (L)
- histidine (H)
- lysine (K)
- valine (V)
- methionine (M)
- threonine (T)
- tryptophan (W)
- phenylalanine (F)
"I Like Having Koala Vision, Monday, Tuesday, Wednesday, and Friday." |
|
|
Term
5-Phosphorybosil-1-pyrophosphate (PRPP)
|
|
Definition
- KEY intermediate/crossing point in:
- amino acid biosynthesis (histidine, trytophan)
- nucleotide biosynthesis (RNA/DNA; purine)
- synthesized from ribose 5-phosphate via ribose phosphate pyrophosphokinase
|
|
|
Term
| a-ketoglutarate as precursor |
|
Definition
glutamate | V glutamine, proline, arginine - proline made directly from glutamate OR from arginine ingested from dietary or tissue protein
|
|
|
Term
|
Definition
- Arginase converts arginine to ornithine and urea
- orthnithine-delta-aminotransferase converts ornithine to glutamate gamma-semialdehyde
- orthnithine-delta-aminotransferase is a key step in proline synthesis in mammals; reversible; mitochondrial matrix
- when not enough arginine in diet, reaction reverses and orthnithine-gamma-aminotransferase creates ornithine --> citrulline-->arginine (ONLY PATHWAY TO ARGININE in MAMMALS)
|
|
|
Term
| Proline & Arginine Synthesis |
|
Definition
GLUTAMATE -->--> GLUTAMATE γ-SEMIALDEHYDE-->-->PROLINE - all 5 carbons of proline derive from glutamate
GLUTAMATE γ-SEMIALDEHYDE--> ORNITHINE--> CITRULLIN--> ARGININE - proline-arginine balance moderated by ornithine δ-aminotransferase (conversion of glutamate γ-semialdehyde to ornithine; reversible)
|
|
|
Term
|
Definition
- serine is first synthesized
- glycine and cysteine both synthesized from serine
- serine hydroxymethyl-transferase removes a carbon from serine to form glycine
- glycine also synthesized from CO2 & NH4+in the liver of vertebrates via glycine cleavage enzyme
|
|
|
Term
|
Definition
- methionine (sulfur group) and serine (carbon skeleton) are components
- in mammals, homocysteine derives from methionine (via S-adenosyl-methionine and S-adenosyl-homocysteine)
|
|
|
Term
|
Definition
synthesized with glutamate via transamination by glutamate aminotransferase; same enzyme also makes alanine from pyruvate & glutamate
synthesized by amidation of aspartate with glutamine (NH4+ donor) via asparagine synthetase- methionine *
- lysine *
- threonine *
|
|
|
Term
|
Definition
- methionine,lysine,threonine (and asparagine)
- branch points at aspartate β-semialdehyde, an intermediate in all 3 pathways
- branch points at homoserine, precursor of threonine and methionine
- threonine is precursor of isoleucine
|
|
|
Term
|
Definition
PYRUVATE + glutamate <--> alanine via aminotransferase activity |
|
|
Term
|
Definition
- tryptophan, tyrosine, phenylalanine
- synthetic pathways ONLY in plants, bacteria, fungi
- CHORISMATE, key intermediate in all 3 pathways, that has carbon atoms originating from:phosphoenolpyruvate (PEP) and erythrose 4-phosphate
|
|
|
Term
| Tyrosine is conditionally essential |
|
Definition
- animals can produce tyrosine directly from phenylalanine through oxidation by phenylalanine hydroxylase
- this enzyme used to balance concentrations of phenylalanine and tyrosine within the cell
|
|
|
Term
|
Definition
- deficiency in phenylalanine hydroxylase enzyme, leading to build-up of phenylalanine and its precursors (phenylpyruvate); also build-up of phenylpyruvate products, phenyllactate and phenylacetate (both toxic)
- low concentration of tyrosine, normally a precursor of: tissue proteins, melanin, catecholamines, fumarate
- symptoms: mental retardation, hyperactivity, tremor, seizures, hypopigmentation
|
|
|
Term
|
Definition
- chorismate intermediate
- PRPP contributes 2carbons for ring
- tryptophan synthetase, key enzyme of last step in pathway
|
|
|
Term
|
Definition
- most complex AA to build
- 3 precursors:
- PRPP (5 carbons)
- ATP (nitrogen, 1 carbon)
- glutamine (nitrogen)
|
|
|
Term
|
Definition
- more sensitive, directed regulation
- an enzyme with several isozyme forms can be regulated uniquely to have much more specific control over particular reaction products
- ie:A1is regulated differently than A2
|
|
|
Term
| sequential feedback inhibition |
|
Definition
for fine-tuning regulation at different points along the pathway; gives cells the ability to precisely adjust the concentration of various products, without broadly shutting down the entire pathway. |
|
|
Term
| Molecules derived from amino acids |
|
Definition
- hormones
- coenzymes
- nucleotides
- alkaloids
- cell wall polymers
- porphyrins (GLYCINE)
- neurotransmitters
- pigments
|
|
|
Term
| Creatine & Phosphocreatine |
|
Definition
- creatine synthesized from glycine & arginine
- methionine (S-adenosyl-methionine) is methyl group donor
- creatine converted to phosphocreatine via creatine kinase (skeletal muscle)
|
|
|
Term
|
Definition
- plants, animals, bacteria
- redox buffer
- PRECURSORS:
|
|
|
Term
| tyrosine as neurotransmitter precursor |
|
Definition
- catecholamines:
- dopamine
- norepinephrine
- epinephrine
DECARBOXYLATION (requires PLP coenzyme)
|
|
|
Term
Glutamate as neurotransmitter precursor |
|
Definition
- GABA (γ-aminobutyrate; inhibitory neurotransmitter)
- glutamate isdecarboxylated
DECARBOXYLATION (requires PLP coenzyme)
|
|
|
Term
| Tryptophan as neurotransmitter precursor |
|
Definition
DECARBOXYLATION (requires PLP coenzyme)
|
|
|
Term
|
Definition
- decarboxylated from histidine
- histamine stimulates allergic response, gastric acid secretion
- cimethidine is a histimine receptor antagonist (Tagamet, promotes healing of duodenal ulcers by inhibiting gastric acid secretion)
|
|
|
Term
|
Definition
- arginine is precursor
- nitric oxide synthase is enzyme
|
|
|
Term
| Polyamines (spermine and spermidine) |
|
Definition
- methionine, ornithine
- ORNITHINE DECARBOXYLASE (decarboxylates ornithine into putrescine...); target of pharmaceutical inhibitors
- spermine and spermidine are required for DNA packaging
- African sleeping sickness theraphy targets this enzyme in Trypanosoma cells via DFMO (difluoromethylornithine), inactivates the enzyme
|
|
|
