Module 12 - Amino Acid Synthesis Flashcards
How many steps are involved in nitrogen assimilation?
3
What is the first step of nitrogen assimilation?
involves the fixation of nitrogen by bacteria that reside in soil and legume root nodules into usable forms such as ammonium, nitrites, and nitrates through the Nitrogen Cycle
What is the overall reaction of nitrogen fixation?
N2 + 10 H+ + 16 ATP + 8 e- →
2 NH4+ + H2 + 16 ADP + 16 Pi
What is the second step of nitrogen assimilation?
it occurs in plants and microorganisms, and involves the incorporation of ammonium into glutamate and glutamine
During the second step of nitrogen assimilation, there are three enzyme-catalyzed reactions. The first one is…
The first reaction is catalyzed by glutamate dehydrogenase
During the second step of nitrogen assimilation, there are three enzyme-catalyzed reactions. The second one is…
The glutamate from the first reaction can then be used in a subsequent reaction to assimilate even more nitrogen; this is catalyzed by glutamine synthetase
Glutamate + NH4+ + ATP → glutamine + ADP + Pi + H+
During the second step of nitrogen assimilation, there are three enzyme-catalyzed reactions. The third and final one is…
The third enzyme that is involved in the assimilation of nitrogen is indirect. Since there is a large need for glutamate because of the second reaction, there is a separate reaction that plants and microorganisms have that ensures that there are high levels of glutamate present. It is catalyzed by glutamate synthase.
α-ketoglutarate + glutamine + NADPH + H+ → 2 glutamate + NADP+
What is the third step of nitrogen assimilation?
Step 3 in the assimilation of nitrogen involves using glutamate to donate its amino group to other α-ketoacids to form most of the other amino acids that are needed in the cell.
This is done by the aminotransferase
if glutamate levels are high, the reaction can flow in the opposite direction and instead, it produces the various amino acids.
What is significant about glutamine synthetase?
It is one of the major enzymes involved in assimilating nitrogen and is the primary regulatory point in nitrogen metabolism in most species.
It is a ubiquitous enzyme, present in all organisms.
Glutamate + NH4+ + ATP → glutamine + ADP + Pi + H+
How is glutamine synthetase regulated?
The regulation of glutamine synthetase is highly complex and involves both covalent modification and allosteric regulation.
There are a total of 8 allosteric inhibitors; all of them are nitrogen-containing biomolecules, 6 are molecules that glutamine is a provider of the nitrogen for their biosynthesis, and the other two are amino acids
The degree of inhibition provided by these 8 inhibitors is more than additive, so that the cumulative effect of two, three or more is greater than the additive effect of each one individually.
What does Adenylylation refer to?
Adenylylation refers to the linking of an AMP molecule to a tyrosine reside through the –OH group of tyrosine, forming an ester bond, using ATP as the donor of the AMP group
What is the consequence of adenylylation?
It acts to sensitize the enzyme to the 8 allosteric inhibitors.
research has shown that a glutamine synthetase that is completely devoid of any adenylylation is essentially insensitive to any of the allosteric inhibitors.
What are the 2 methods for one-carbon transfer reactions?
S-adenosylmethionine (SAM), which adds methyl groups
tetrahydrofolate, which carries a variety of one-carbon units.
Why is SAM used rather than simply methionine?
The methyl group in methionine is not very reactive.
What is the general reaction that SAM participates in?
in a SAM reaction, which enzymes transfer the methyl group to their specific substrates?
methyltransferases
In a SAM reaction, where are methyl groups almost always transferred to?
a nitrogen or oxygen atom
How is epinephrine synthesized from norepinephrine?
in a reaction that requires a methyl group transfer from SAM onto a nitrogen atom in norepinephrine.
Where is tetrahydrofolate derived from?
the vitamin folate (B9)
In tetrahydrofolate, the source of the one-carbon units is either?
serine or formate
Formate is the source of oxygen as well.
Amino Group Transfers
amino groups get added on by which group?
glutamine and sometimes glutamate act as donors of these groups
All amino acids are synthesized from specific intermediates of three metabolic pathways. Which are?
glycolysis, pentose phosphate pathway, and the citric acid cycle
The biosynthetic pathways for the 20 amino acids can be grouped according to 6 metabolic precursors
α-ketoglutarate
pyruvate
3-phosphoglycerate
oxaloacetate
ribose 5-phosphate, and
phosphoenolpyruvate/erythrose 4-phosphate
Amino acid biosynthetic families, grouped by metabolic precursor.
not all organisms have the necessary enzymes to synthesize all 20 amino acids
Most bacteria and plants can synthesize all of them, while mammals can only synthesize some and the rest are required in the diet
What are the amino acids that we can synthesize are called?
non-essential amino acids
What are the amino acids called that are required in our diet?
essential amino acids
What are amino acids that are termed conditionally essential?
they are essential only during specific times such as during growth, such as in young, growing babies, or in individuals experiencing some specific illness which generates an increased demand for protein synthesis.
five amino acids that can be synthesized from oxaloacetate, an intermediate of the citric acid cycle.
plus four amino acids that can be synthesized from pyruvate.
How are amino acid synthetic pathways regulated?
there are different types of feedback inhibition (often called product inhibition) that exist that allow tight control of how much of each is synthesized
What is Product Inhibition?
a generic term that refers to a situation where the end product (lets call it F) acts as an allosteric inhibitor of the first committed step in the pathway
This prevents unnecessary production of F when levels are sufficiently high
What is Sequential Inhibition?
there is a sequence of events that controls the overall flux through the pathways
F and G inhibit the conversion of C to D and E, and C acts back on the conversion of A to B
What is Concerted Inhibition?
the two end products F and G both inhibit the same enzyme, the one that catalyzes the first committed step in the overall pathway
One important feature of this type of inhibition is that the combined effect of F and G is more than additive; that is, their combined effect is greater than their effects individually if you just added them together.
What is Enzyme Multiplicity?
the first committed step in the pathway is catalyzed by two isoenzymes, which are enzymes that catalyze the same reaction but are coded for by different genes and thus may have specific properties.
