Biosynthesis
In
.The prerequisite elements for biosynthesis include:
Properties of chemical reactions
Biosynthesis occurs due to a series of chemical reactions. For these reactions to take place, the following elements are necessary:[1]
- reactantsin a given chemical process.
- phosphates. Often, the terminal phosphate is split off during hydrolysis and transferred to another molecule.
- coenzymes and they catalyze a reaction by increasing the rate of the reaction and lowering the activation energy.
In the simplest sense, the reactions that occur in biosynthesis have the following format:[2]
Some variations of this basic equation which will be discussed later in more detail are:[3]
- Simple compounds which are converted into other compounds, usually as part of a multiple step reaction pathway. Two examples of this type of reaction occur during the formation of tRNA prior to translation. For some of these steps, chemical energy is required:
- Simple compounds that are converted into other compounds with the assistance of cofactors. For example, the synthesis of phospholipids requires acetyl CoA, while the synthesis of another membrane component, sphingolipids, requires NADH and FADH for the formation the sphingosine backbone. The general equation for these examples is:
- Simple compounds that join to create a macromolecule. For example, noncovalently in order to form the lipid bilayer. This reaction may be depicted as follows:
Lipid
Many intricate macromolecules are synthesized in a pattern of simple, repeated structures. Fatty acid chains are found in two major components of membrane lipids:
Phospholipids
The foundation of all biomembranes consists of a
There are various types of phospholipids; consequently, their synthesis pathways differ. However, the first step in phospholipid synthesis involves the formation of
The pathway starts with glycerol 3-phosphate, which gets converted to lysophosphatidate via the addition of a fatty acid chain provided by
Sphingolipids
Like phospholipids, these fatty acid derivatives have a polar head and nonpolar tails.
Sphingolipids are formed from ceramides that consist of a fatty acid chain attached to the amino group of a sphingosine backbone. These ceramides are synthesized from the acylation of sphingosine.[11] The biosynthetic pathway for sphingosine is found below:
As the image denotes, during sphingosine synthesis,
Cholesterol
This
Cholesterol is synthesized from
More generally, this synthesis occurs in three stages, with the first stage taking place in the cytoplasm and the second and third stages occurring in the endoplasmic reticulum.[9] The stages are as follows:[12]
- 1. The synthesis of isopentenyl pyrophosphate, the "building block" of cholesterol
- 2. The formation of squalene via the condensation of six molecules of isopentenyl phosphate
- 3. The conversion of squalene into cholesterol via several enzymatic reactions
Nucleotides
The biosynthesis of
Purine nucleotides
The DNA nucleotides
- The first step in purine biosynthesis is a .
- GAR synthetase[15] performs the condensation of activated glycine onto PRPP, forming glycineamide ribonucleotide (GAR).
- formyl grouponto the amino group of GAR, forming formylglycinamide ribonucleotide (FGAR).
- FGAR amidotransferase[16] catalyzes the addition of a nitrogen group to FGAR, forming formylglycinamidine ribonucleotide (FGAM).
- FGAM cyclase catalyzes ring closure, which involves removal of a water molecule, forming the 5-membered imidazole ring 5-aminoimidazole ribonucleotide (AIR).
- N5-CAIR synthetase transfers a carboxyl group, forming the intermediate N5-carboxyaminoimidazole ribonucleotide (N5-CAIR).[17]
- carboxyamino- imidazole ribonucleotide (CAIR). The two step mechanism of CAIR formation from AIR is mostly found in single celled organisms. Higher eukaryotes contain the enzyme AIR carboxylase,[18]which transfers a carboxyl group directly to AIR imidazole ring, forming CAIR.
- aspartate and the added carboxyl group of the imidazole ring, forming N-succinyl-5-aminoimidazole-4-carboxamide ribonucleotide(SAICAR).
- SAICAR lyase removes the carbon skeleton of the added aspartate, leaving the amino group and forming 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR).
- AICAR transformylase transfers a carbonyl group to AICAR, forming N-formylaminoimidazole- 4-carboxamide ribonucleotide(FAICAR).
- The final step involves the enzyme IMP synthase, which performs the purine ring closure and forms the inosine monophosphate intermediate.[5]
Pyrimidine nucleotides
Other DNA and RNA nucleotide bases that are linked to the ribose sugar via a glycosidic bond are thymine, cytosine and uracil (which is only found in RNA). Uridine monophosphate biosynthesis involves an enzyme that is located in the mitochondrial inner membrane and multifunctional enzymes that are located in the cytosol.[19]
- The first step involves the enzyme CO2 in an ATP dependent reaction to form carbamoyl phosphate.
- Aspartate carbamoyltransferase condenses carbamoyl phosphate with aspartate to form uridosuccinate.
- dihydroorotate.
- orotate.
- Orotate phosphoribosyl hydrolase (OMP pyrophosphorylase) condenses orotate with PRPP to form orotidine-5'-phosphate.
After the uridine nucleotide base is synthesized, the other bases, cytosine and thymine are synthesized. Cytosine biosynthesis is a two-step reaction which involves the conversion of UMP to
Cytosine is a nucleotide that is present in both DNA and RNA. However, uracil is only found in RNA. Therefore, after UTP is synthesized, it is must be converted into a
In contrast to uracil, thymine bases are found mostly in DNA, not RNA. Cells do not normally contain thymine bases that are linked to ribose sugars in RNA, thus indicating that cells only synthesize deoxyribose-linked thymine. The enzyme
DNA
Although there are differences between
In order for DNA replication to occur, a
DNA synthesis is initiated by the RNA polymerase primase, which makes an RNA primer with a free 3'OH.[23] This primer is attached to the single-stranded DNA template, and DNA polymerase elongates the chain by incorporating nucleotides; DNA polymerase also proofreads the newly synthesized DNA strand.[23]
During the polymerization reaction catalyzed by DNA polymerase, a
Two types of strands are created simultaneously during replication: the
Amino acids
A protein is a polymer that is composed from
Amino acid basic structure
The diaminopimelic acid biosynthetic pathway of lysine belongs to the aspartate family of amino acids. This pathway involves nine enzyme-catalyzed reactions that convert aspartate to lysine.[43]
- phosphoryl from ATP onto the carboxylate group of aspartate, which yields aspartyl-β-phosphate.[44]
- Aspartate-semialdehyde dehydrogenase catalyzes the reduction reaction by dephosphorylation of aspartyl-β-phosphate to yield aspartate-β-semialdehyde.[45]
- Dihydrodipicolinate synthase catalyzes the condensation reaction of aspartate-β-semialdehyde with pyruvate to yield dihydrodipicolinic acid.[46]
- 4-hydroxy-tetrahydrodipicolinate reductase catalyzes the reduction of dihydrodipicolinic acid to yield tetrahydrodipicolinic acid.[47]
- Tetrahydrodipicolinate N-succinyltransferase catalyzes the transfer of a succinyl group from succinyl-CoA on to tetrahydrodipicolinic acid to yield N-succinyl-L-2,6-diaminoheptanedioate.[48]
- N-succinyldiaminopimelate aminotransferase catalyzes the transfer of an amino group from glutamate onto N-succinyl-L-2,6-diaminoheptanedioate to yield N-succinyl-L,L-diaminopimelic acid.[49]
- Succinyl-diaminopimelate desuccinylase catalyzes the removal of acyl group from N-succinyl-L,L-diaminopimelic acid to yield L,L-diaminopimelic acid.[50]
- meso-diaminopimelic acid.[51]
- Siaminopimelate decarboxylase catalyzes the final step in lysine biosynthesis that removes the carbon dioxide group from meso-diaminopimelic acid to yield L-lysine.[52]
Proteins
Protein synthesis occurs via a process called
Additional background
Before translation can begin, the process of binding a specific amino acid to its corresponding tRNA must occur. This reaction, called tRNA charging, is catalyzed by aminoacyl tRNA synthetase.[54] A specific tRNA synthetase is responsible for recognizing and charging a particular amino acid.[54] Furthermore, this enzyme has special discriminator regions to ensure the correct binding between tRNA and its cognate amino acid.[54] The first step for joining an amino acid to its corresponding tRNA is the formation of aminoacyl-AMP:[54]
This is followed by the transfer of the aminoacyl group from aminoacyl-AMP to a tRNA molecule. The resulting molecule is aminoacyl-tRNA:[54]
The combination of these two steps, both of which are catalyzed by aminoacyl tRNA synthetase, produces a charged tRNA that is ready to add amino acids to the growing polypeptide chain.
In addition to binding an amino acid, tRNA has a three nucleotide unit called an
There are numerous codons within an mRNA transcript, and it is very common for an amino acid to be specified by more than one codon; this phenomenon is called degeneracy.[57] In all, there are 64 codons, 61 of each code for one of the 20 amino acids, while the remaining codons specify chain termination.[57]
Translation in steps
As previously mentioned, translation occurs in three phases: initiation, elongation, and termination.
Step 1: Initiation
The completion of the initiation phase is dependent on the following three events:[13]
1. The recruitment of the ribosome to mRNA
2. The binding of a charged initiator tRNA into the P site of the ribosome
3. The proper alignment of the ribosome with mRNA's start codon
Step 2: Elongation
Following initiation, the polypeptide chain is extended via anticodon:codon interactions, with the ribosome adding amino acids to the polypeptide chain one at a time. The following steps must occur to ensure the correct addition of amino acids:[58]
1. The binding of the correct tRNA into the A site of the ribosome
2. The formation of a peptide bond between the tRNA in the A site and the polypeptide chain attached to the tRNA in the P site
3.
Translocation "kicks off" the tRNA at the E site and shifts the tRNA from the A site into the P site, leaving the A site free for an incoming tRNA to add another amino acid.
Step 3: Termination
The last stage of translation occurs when a stop codon enters the A site.[1] Then, the following steps occur:
1. The recognition of codons by release factors, which causes the hydrolysis of the polypeptide chain from the tRNA located in the P site[1]
2. The release of the polypeptide chain[57]
3. The dissociation and "recycling" of the ribosome for future translation processes[57]
A summary table of the key players in translation is found below:
Key players in Translation | Translation Stage | Purpose |
---|---|---|
tRNA synthetase | before initiation | Responsible for tRNA charging |
mRNA | initiation, elongation, termination | Template for protein synthesis; contains regions named codons which encode amino acids |
tRNA | initiation, elongation, termination | Binds ribosomes sites A, P, E; anticodon base pairs with mRNA codon to ensure that the correct amino acid is incorporated into the growing polypeptide chain |
ribosome | initiation, elongation, termination | Directs protein synthesis and catalyzes the formation of the peptide bond |
Diseases associated with macromolecule deficiency
Errors in biosynthetic pathways can have deleterious consequences including the malformation of macromolecules or the underproduction of functional molecules. Below are examples that illustrate the disruptions that occur due to these inefficiencies.
- atherosclerotic plaques that narrow arteries and increase the risk of heart attacks.[59]
- self- mutilation, mental deficiency, and gout.[60] It is caused by the absence of hypoxanthine-guanine phosphoribosyltransferase, which is a necessary enzyme for purine nucleotide formation.[60] The lack of enzyme reduces the level of necessary nucleotides and causes the accumulation of biosynthesis intermediates, which results in the aforementioned unusual behavior.[60]
- dATP. These dATP molecules then inhibit ribonucleotide reductase, which prevents of DNA synthesis.[61]
- cognitive decline, and behavioral disorder.[63]
See also
- Lipids
- Phospholipid bilayer
- Nucleotides
- DNA
- DNA replication
- Proteinogenic amino acid
- Codon table
- Prostaglandin
- Porphyrins
- Chlorophylls and bacteriochlorophylls
- Vitamin B12
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