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27 Cards in this Set

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  • Back

What does their rate of amino acid synthesis depend on?

Amounts of amino acids and their activities.

What process controls amino acid synthesis?

Feedback inhibition and feedback activation.

Which amino acids share the same initial substrate: Hydroxyethyl - TPP?

1. Valine


2. Isoleucine


3. Leucine

How is the synthesis of Isoleucine controlled?
Isoleucine shares a common pathway with valine and leucine and thus these amino acids balance each other. 
Production of isoleucine requires the enzyme Threonine deaminase to produce alpha-ketobutyrate to combine with Hydroxyethyl-TPP. 
Valine doe...

Isoleucine shares a common pathway with valine and leucine and thus these amino acids balance each other.


Production of isoleucine requires the enzyme Threonine deaminase to produce alpha-ketobutyrate to combine with Hydroxyethyl-TPP.


Valine does not require this enzyme to be produced from the SAME substrate. Valine has a feedback activation pathway which increases the activity of Threonine deaminase. Thus, Valine production controls Isoleucine synthesis through a process of feedback activation.

What is the critical enzyme in the synthesis of isoleucine?

Threonine Deaminase.

What is concerted feedback inhibition?


What enzyme + pathway is controlled by this process?


What is the critical quality of an enzyme controlled by this process?

Where many products produce a partial feedback inhibitory effect on a singular enzyme.


Glutamine synthetase in the glutamine synthetase.


High allosterity - many binding sites linked to control.

What is enzyme multiplicity?


Where is this commonly observed?

Many enzyme isozymes for a single step in a pathway.


As this prevents inhibition from stopping a critical pathway it can be observed in very fast growing bacteria where the products of the pathway are required en masse for growth of the cell.

What components is histidine ultimately derived from?


What part does each component contribute towards the final formation?

3 precursors:

1. PRPP - 5 carbons


2. ATP - 1 Nitrogen + 1 Carbon


3. Glycine - 2nd ring carbon


How does histidine biosynthesis begin?



ATP nucleophilically attacks PRPP to form an ATP PRPP compound - N' - 5' phosphoribosyl-ATP.

What pathway is linked to the histidine pathway?


How?

The purine biosynthesis pathway is linked to the histidine pathway.


An intermediate is 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) which is a purine pathway precursor.

What are Nucleosides?


What is the linkage?

Nucleosidesa are bases joined to sugars via a Beta glycosidic linkage.

What are Nucleotides?


What is the basic synthesis process?

Nucelotides are simply phosphate esters of nucleotides built one at a time in a linear fashion.

How is the synthesis of AMP and GMP linked?

Share the same initial precursor - Inosinate

What is the basic AMP synthesis pathway?

Inosinate + Pi (from GTP) + Aspartate --> Adenylosuccinate


Adenylosuccinate then has the majority of the Aspartate residue cleaved to leave a nitrogen and release fumarate.

What is the basic GMP synthesis pathway

Inosinate + NAD+ + H2O --> Xanthlyate + NADH + H+ (oxidised)


Xanthylate + H3N + Glutamine + ATP ---> Guanylate (GMP)

What do both AMP and GMP synthesis have in common?

Both require ATP for their synthesis and both share the same precursor.

How is purine synthesis controlled?

GMP and AMP have multiple feedback inhibition routes.


1. GMP and AMP will inhibit their own production to balance concentrations of each evenly.


2. Both will inhibit the overall rate of purine biosynthesis.

What processes do GMP and AMP control? How?


What does this achieve.

Through a process of feedback inhibition GMP and AMP will control the inhibit the conversion of ribose-5-phosphate to PRPP - the critical first step which allows purine synthesis.


Also control the conversion of PRPP --> phosphoribosylamine (A precursor to the AMP -> GMP pathways.




Ultimately this achieves the balancing of GMP and AMP and prevents the domination of the pathway over the PRPP --> histidine / pyrimidine pathways.


It also controls the rate of any sort of PRPP related pathway.

What is De novo synthesis?

Where complex molecules are formed from the most basic molecules rather than recycled and partially degraded complex molecules.

What is the critical enzyme in the de novo synthesis of pyrimidines?


What is the significance of this?


How is it controlled?

Aspartate --> N-Carbamylaspartate


The enzyme which controls this initial step is - Aspartate transcarbamoylase feedback inhibited by the final product of the pathway. This controls the rate of this pathway.

What is the feedback inhibitor in the de novo synthesis of pyrimidines?

The final product - Cytidine 5' triphosphate (CTP)

What is the role of CTP?


What does it stand for?

Cytidine triphosphate (CTP) makes pyrimidines in the cytosol.

How are the basics of deoxynucleotide synthesis?

From ribonucleotides:


1. Formed by reduction of ribonucleotides (2'Oh --> 2' H


2. substrates are rNDP or rNTP


3. Reductant is NADPH



What role does NADPH play in the deoxynucleotide synthesis pathway?

Passes electrons to the ribonucleotide reductase enzyme from:


1. Glutaredoxin


2. Thioredoxin

What are ribonucleotide reductases?



A diverse group of enzymes which reduce all 4 nucleotides

What is the best studied example of ribonucleotide reductases?


What are the details of this study (Structure + functional details) ?

E.coli --> where the enzyme exists as two subunits and act as a dimer.


R1 and R2.


R1 is the active unit


R2 is the regulatory unit.




Critically (!) the overall dimer is allosterically controlled in two unique ways. One control site is allosterically controlling the rate of synthesis and the other controls the specificity to the substrate.

In the E.coli ribonucleotide reductase what are the critical amino acid residues in the:


R1 subunit (catalytic)


R2 subunit (regulatory)


?

R1 - 1x Glutamine residue + 3x Cysteine residue


R2 - Stable free radical on a Tyrosine residue