Fact 2
Prebiotic forces cannot create the basic building blocks needed for the development of the basic cell.
FOUR MOLECULES are needed for life: nucleotides, carbohydrates, proteins, and lipids.
“Nobody has shown a method to make the enantiopure versions of carbohydrates, amino acids, nucleotides or lipids in a prebiotically relevant manner”
— Dr James Tour
Prebiotic Building Blocks
Molecules are the language of living systems
The Building Blocks of Building Blocks
Scientists Deceive Public. Dr. Rob Stadler Dissects Origin of Life Science Claims on RNA Replication
Make the simplest cells - 4 building blocks
Carbohydrate Carbohydrates are organic molecules made up of carbon (C), hydrogen (H), and oxygen (O), typically with a ratio of 1:2:1 (general formula: ). They are essential for life and serve as a major energy source and structural component for living organisms.
Dr Tour, a synthetic organic chemist from Rice University, discusses many problems with carbohydrate formation.
Primary issues are Instability, selective synthesis, and cross reactivity.
Sugar Problem - random connections (non-covalent bonds)of just 6 sugars can combine in a trillion ways.
Nobody has solved the carbohydrate polymerization problem
Six repeat units of a reducing hexasaccharide (like 0-glucose, shown) can form more than one trillion different hexasaccharides through branching (constitutional) and glycosidic (stereochemical) diversity.
Roger Laine, "Invited eommentary: A Calculation of All Possible Oligosaccharide Isomers Both Branched and Linear Yields 1.05 x 1012 Structures for a Reducing Hexasaccharide: The Isomer Barrier to Development of Single-Method Saccharide Sequencing or Synthesis Systems," Glycobiology 4, no. 6 (1994): 759-67, doi:10.1093/glycob/4.6.759.
The Problem of Carbohydrate Formation in Prebiotic Chemistry
In the context of origin-of-life research, forming carbohydrates under prebiotic conditions is a major challenge because:
1. Instability
Tour argues that no known prebiotic synthesis provides a realistic pathway to form nucleotides—molecules that make up RNA and DNA—under early Earth conditions. He highlights that forming nucleotides requires multiple specific chemical steps, each needing precise conditions (e.g., pH, temperature, and concentration of reactants), which are difficult to envision occurring spontaneously.
2. Selective Synthesis
Prebiotic conditions often produce a mixture of sugars with various chain lengths and structures, making it hard to get only biologically relevant ones.
3. Cross-Reactivity
Sugars can react with other molecules in ways that destroy their usefulness for life.
Dr. James Tour highlights that these challenges make it difficult to explain how carbohydrates, especially complex ones like polysaccharides, could have formed and accumulated in the right conditions to support the emergence of life.
Rice Professor Demands Transparency on Origin of Life Chemistry
Proteins
Credit: Erin Rod
Proteins are large, complex molecules made of amino acids. They are essential for virtually every biological process, performing structural, enzymatic, transport, and signaling functions in living organisms. The proteins are molecular machines intentionally directed to perform a particular function. Over a hundred different proteins are needed in a simple cell for life.
Major problems forming these prebiotically. Prebiotically, the correct structure of Amino acids is not prevalent, instability, improper sequencing and no mechanism to fold up in the correct order. Here is a simple protein:
Transcription - RNA Polymerase
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RNA polymerase is an enzyme responsible for synthesizing RNA from a DNA template in a process called transcription. It plays a key role in gene expression by copying genetic information from DNA into messenger RNA (mRNA), which is later translated into proteins.
1. Transcription
Synthesizes RNA by adding ribonucleotides (A, U, C, G) in a 5’ to 3’ direction.
2. Initiation
Binds to DNA at the promoter region and starts RNA synthesis.
3. Elongation
Moves along the DNA, adding ribonucleotides to the growing RNA strand.
4. Termination
Stops transcription at specific sequences and releases the RNA molecule. Eukaryotic RNA polymerases are much more complex, consisting of multiple subunits:
RNA Polymerase I – 14 subunits
RNA Polymerase II – 12 subunits
RNA Polymerase III – 17 subunits
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General Structure
Bacterial RNA Polymerase: A well-studied example is Escherichia coli RNAP, which has a core enzyme composed of five subunits: α₂ββ’ω (approximately 400 kDa total). Each subunit is a distinct polypeptide chain made of amino acids.
α subunit: ~329 amino acids each (two copies).
β subunit: ~1,342 amino acids.
β’ subunit: ~1,552 amino acids.
ω subunit: ~91 amino acids.
A sixth subunit, σ (sigma factor, e.g., σ⁷⁰ with ~613 amino acids), joins temporarily to initiate transcription.
Eukaryotic RNA Polymerase II: More complex, with 12 subunits (Rpb1–Rpb12) in humans. The largest subunit, Rpb1, contains ~1,970 amino acids, while smaller subunits range from ~70 to 500 amino acids each.
Total Amino Acids: The exact count depends on the species and polymerase type, but bacterial RNAP has roughly 4,000–5,000 amino acids across its subunits, and eukaryotic RNAP II exceeds 5,000.
Transcription video - multiple proteins join together to form the machine, specific location on the DNA must be targeted, the machine rapidly moves, splits the DNA strand, copies the DNA, makes an identical RNA copy and puts the DNA back together.
You have over 37 trillion living cells in your body, everyone of them is does this process repeatedly throughout the day.
DNA Transcription (Basic)
The Origin-of-Life Problem with Proteins
Dr. James Tour highlights several issues related to protein formation in prebiotic environments:
1. Amino Acid Synthesis
While some amino acids can be synthesized in controlled lab settings, the correct types and chirality (left-handed form for life) are difficult to produce in the right proportions.
2. Peptide Bond Formation
Amino acids must form stable peptide bonds to create functional proteins, but in prebiotic conditions, this reaction is highly inefficient and prone to hydrolysis.
3. Correct Sequencing
Proteins require a specific sequence of amino acids for proper folding and function. Random sequences are unlikely to result in functional proteins.
4. Stability
Even if short peptides form, they are easily broken down in harsh environmental conditions.
Polymers
Peptides - Inconceivable
Protein Fold Problem
Amino Acid Fold
Lipids
Lipids are a diverse group of hydrophobic or amphiphilic molecules, primarily composed of carbon, hydrogen, and oxygen. They play crucial roles in energy storage, membrane structure, and signaling.
Lipids in Origin-of-Life Research
In the origin-of-life debate, the formation and organization of lipids into protocells (primitive cell-like structures) is a key focus. However, there are major challenges:
1. Prebiotic Synthesis
The formation of complex lipids (like phospholipids) under prebiotic conditions is difficult and poorly understood.
2. Selective Assembly
For life to emerge, lipids must form stable, selectively permeable membranes—a challenging feat without cellular machinery.
3. Membrane Stability
Early membranes would be prone to degradation in harsh environments, reducing the chances of forming and maintaining protocells. Despite these challenges, lipids are considered vital to the emergence of the first cells, as they provide compartmentalization, a critical step toward organized biochemical processes.
Cell Membrane
The Complex Cellular Membrane
Researchers have identified thousands of different lipid structures in cell membranes.
When making synthetic vesicles-synthetic lipid bilayer membranes-mixtures with monoacyl lipids can destabilize the system- so how are these avoided?Lipid bilayers surround subcellular organelles, such as nuclei and mitochondria, which are themselves microsystem assemblies. Each of these has their own lipid composition, different from the host vesicle.
Lipid bilayers have a non-symmetric distribution between inner and outer surfaces.
Protein-lipid complexes are the required passive transport sites and active pumps for the passage of ions and molecules through bilayer membranes, often with high specificity.
All lipid bilayers have vast numbers of polycarbohydrate appendages, known as glycans. These are essential for cell regulation. Consider the hexamer of the carbohydrate D-pyranose→ >1 trillion constitutional and stereochemical isomers. Eliminating any class of carbohydrates from an organism results in its death.