Conditionally essential amino acids
Some amino acids cannot be synthesized from ordinary carbohydrates or fats because they require specific carbon structures. They are formed exclusively from essential amino acids obtained through the diet. This group includes:
- Tyrosine — synthesized via hydroxylation of essential phenylalanine.
- Cysteine — its formation requires essential methionine, which acts as a sulfur donor.
Precursors of non-essential amino acids
Non-essential amino acids are built on the basis of carbohydrate metabolism metabolites (glycolysis and the citric acid cycle). The process of their formation typically involves the transfer of an amino group to a keto acid.
Key matches between precursors and products:
- Alanine. Formed from pyruvate via a transamination reaction catalyzed by the enzyme alanine aminotransferase (ALT).
- Asparagine. Synthesized from aspartate via amidation, where glutamine serves as the source of the additional amino group.
- Proline. Its molecule is formed from glutamate, with glutamate semialdehyde serving as an intermediate.
- Serine. The source for its biosynthesis is the glycolytic intermediate 3-phosphoglycerate. Serine itself can subsequently serve as a building block for the synthesis of glycine and cysteine.
Regeneration of aspartate and nitrogen sources
Aspartate is actively used in metabolic pathways, such as the urea cycle (ornithine cycle). After nitrogen cleavage, the carbon skeleton is released as fumarate.
Restoration of the aspartate pool follows this pathway: fumarate is converted into malate and then oxidized to oxaloacetate. The final step involves transamination of oxaloacetate. The main donor of the $NH_2$ group in this reaction is glutamate. If glutamate stores are depleted, nitrogen can be supplied by other amino acids that first transfer their amino groups to alpha-ketoglutarate, replenishing the total glutamate pool.
Calculation of aspartate biosynthesis from glucose
Let us examine the multistep process of aspartate formation using the breakdown of 6 mol of glucose as an example. The process includes three main stages:
1. Aerobic glycolysis The breakdown of glucose yields pyruvate. The reaction stoichiometry is such that 1 mol of glucose produces 2 mol of pyruvate, 2 mol of ATP, and 2 mol of NADH. Consequently, 12 mol of pyruvate is synthesized from 6 mol of glucose.
2. Pyruvate carboxylation Pyruvate is converted into the keto analogue of aspartate — oxaloacetate. The reaction proceeds with the expenditure of ATP and the addition of carbon dioxide under the action of the enzyme pyruvate carboxylase. A crucial coenzyme for this reaction is biotin. Exactly 12 mol of oxaloacetate is formed from 12 mol of pyruvate.
3. Transamination Oxaloacetate interacts with glutamate to form aspartate and alpha-ketoglutarate. The reaction is catalyzed by aspartate aminotransferase (AST). This enzyme requires pyridoxal phosphate (the active form of vitamin B6) as a coenzyme. As a result, 12 mol of aspartate is obtained from 12 mol of oxaloacetate.
Briefly: answers to topical questions
Which enzyme catalyzes the formation of asparagine from aspartate?
The formation of asparagine from aspartate is catalyzed by the enzyme asparagine synthetase. This enzyme belongs to the class of ligases (synthetases) and carries out an amidation reaction. It utilizes ATP energy to form a chemical bond, with the process accompanied by the hydrolysis of ATP to AMP and pyrophosphate. The substrates of the reaction are aspartate and glutamine, where glutamine acts as the direct donor of the amide group for the synthesis of the new amino acid.
Which enzymes participate in the conversion of fumarate to oxaloacetate during aspartate regeneration?
Two enzymes participate in the conversion of fumarate to oxaloacetate within the aspartate regeneration cycle:
- Fumarase — catalyzes the hydration of fumarate to form malate.
- Malate dehydrogenase — carries out the oxidation of malate to oxaloacetate (with the simultaneous production of NADH).
These reactions occur in the tricarboxylic acid cycle and ensure the continuous production of oxaloacetate, which is then converted back into aspartate via transamination.
Which enzyme and coenzyme participate in the synthesis of glycine from serine?
Serine hydroxymethyltransferase participates in the synthesis of glycine from serine, with tetrahydrofolate ($H_4$-folate) acting as the coenzyme. During the catalyzed reaction, tetrahydrofolate attaches the $\beta$-carbon atom of serine, forming methylene-$H_4$-folate. Through this specific metabolic pathway, the carbon fragment is cleaved, and the serine molecule is successfully converted into glycine and water.
To memorize the precursors of conditionally essential amino acids, use the mnemonic: "PheT MetC" (Phenylalanine gives Tyrosine, Methionine gives Cysteine).
Class and exam questions
What substance is serine formed from?
Serine is synthesized from 3-phosphoglycerate, which is an intermediate metabolite of glycolysis.
Which vitamins are required for the synthesis of aspartate from pyruvate?
Biotin (for pyruvate carboxylase function at the oxaloacetate formation stage) and vitamin B6 as pyridoxal phosphate (for the AST enzyme during transamination) are required.
What acts as the nitrogen donor in the formation of asparagine?
Glutamine acts as the amino group donor in the aspartate amidation reaction.
What else to study on this topic
- Mechanism of action of aminotransferases (ALT and AST)
- The role of pyridoxal phosphate in transamination reactions
- The link between the ornithine cycle and the tricarboxylic acid cycle
- Biochemical functions of biotin in carboxylation reactions
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