The amazing fatty acid synthase nano factories, and origin of life scenarios
The four basic categories of molecules for building life are carbohydrates, lipids, proteins, and nucleic acids. Here we will give a closer look at fatty acids, constituents of lipids, and their biosynthesis.
Lipids (‘fats’) are essential for the formation of a cell membrane that contains the cell contents, as well as for other cell functions. The cell membrane, comprised of several different complex lipids, is an essential part of a free-living cell that can reproduce itself.
Lipids have much higher energy density than sugars or amino acids, so their formation in any chemical soup is a problem for origin of life scenarios (high energy compounds are thermodynamically much less likely to form than lower energy compounds). Fatty acids are hydrocarbon chains of various lengths. The ability to synthesize a variety of lipids is essential to all organisms. Fatty acid synthesis requires the oxidation of the co-factor NADPH.
The major source of NADPH in animals and other non-photosynthetic organisms is the pentose phosphate pathway. Due to the complexity of the metabolic pathways, it has been argued that metabolism"like chemical reaction sequences are unlikely to be catalysed by simple environmental catalysts.
This constitutes a serious problem for naturalistic explanations of the origin of life. The pentose phosphate pathway requires 7 enzymes, and is interdependent with glycolysis , since the beginning molecule for the pentose phosphate pathway is glucose-6-P, which is the second intermediate metabolite in glycolysis.
Eukaryotic cells face a dilemma in providing suitable amounts of substrate for fatty acid synthesis. Sufficient quantities of acetyl-CoA, malonyl-CoA, and NADPH must be generated in the cytosol for fatty acid synthesis. Malonyl-CoA is made by carboxylation of acetyl-CoA, so the problem reduces to generating sufficient acetyl-CoA and NADPH. There are three principal sources of acetyl-CoA. The acetyl-CoA derived from amino acid degradation is normally insufficient for fatty acid biosynthesis, and the acetyl-CoA produced by pyruvate dehydrogenase and by fatty acid oxidation cannot cross the mitochondrial membrane to participate directly in fatty acid synthesis. Instead, acetyl-CoA is linked with oxaloacetate to form citrate, which is transported from the mitochondrial matrix to the cytosol by citrate carriers (CIC), nuclear-encoded proteins located in the mitochondrial inner membrane, members of the mitochondrial carrier family. Biosynthesis of oxaloacetate requires malate dehydrogenase enzymes or, in plants, pyruvate carboxylase enzymes.
So all these listed functional units and substrates are required in the synthesis process. They are essential, constituting a interdependent interlocked system of the cell.
As Bruce Alberts said in 1998, the biology of the future was going to be the study of molecular machines: “the entire cell can be viewed as a factory that contains an elaborate network of interlocking assembly lines, each of which is composed of a set of large protein machines." One of those machines is like a mini-factory in itself. It’s called fatty acid synthase.
The first step of fatty acid biosynthesis requires the participation of malonyl-CoA, a three-carbon intermediate. The formation of malonyl-CoA from acetyl-CoA is an irreversible process, catalyzed by acetyl-CoA carboxylase enzymes. a multifunctional protein with 3 subunits, which is carefully regulated.
In the second step, fatty acid synthase ( FAS) proteins come into action. These are the little heroes of this article. FAS most striking feature is the “high degree of architectural complexity" – some 48 active sites, complete with moving parts
Which organism has one of the most elaborate fatty-acid machines of all? The surprising answer: fungi.
Perhaps the most striking feature of fungal FAS is its high degree of architectural complexity, in which 48 functional centers exist in a single … particle. Detailed structural information is essential for delineating how this complex particle coordinates the reactions involved in many steps of synthesis of fatty acids… The six alpha subunits form a central wheel in the assembly, and the beta subunits form domes on the top and bottom of the wheel, creating six reaction chambers within which each Acyl Carrier Protein (ACP) can reach the six active sites through surprisingly modest movements.
The crystal structure of yeast FAS reveals that this large, macromolecular assembly functions as a six-chambered reactor for fatty acid synthesis. Each of the six chambers functions independently and has in its chamber wall all of the catalytic units required for fatty acid priming, elongation, and termination, while one substrate-shuttling component, ACP, is located inside each chamber and functions like a swinging arm. Surprisingly, however, the step at which the reactor is activated must occur before the complete assembly of the particle since the PPT domain that attaches the pantetheine arm to ACP lies outside the assembly,inaccessible to ACP that lies inside. Remarkably, the architectural complexity of the FAS particle results in the simplicity of the reaction mechanisms for fatty acid synthesis in fungi.
To imagine this level of precision and master-controlled processing on a level this small, cannot help but induce a profound sense of wonder and awe. Here, all this time, this machine has been helping to keep living things functioning and we didn’t even know the details till now.
The fatty acids are useless without the amino acids, and vice versa . Even if some kind of metabolic cycle were to be envisioned under semi-realistic conditions, how did this elaborate machine, composed of amino acids with precise charge distributions, arise? It’s not just the machine, it’s the blueprints and construction process that must be explained. What blind process led to the precise placement of active sites that process their inputs in a programmed sequence? What put them into a structure with shared walls where six reaction chambers can work independently? All this complexity, involving thousands of precision amino acids in FAS has to be coded in DNA, then built by the formidably complex translation process, then assembled together in the right order, or FAS won’t work. But the storage, retrieval, translation and construction systems all need the fatty acids, too, or they won’t work.
We are witnessing an interdependent system of mind-boggling complexity that defies any explanation besides intelligent design. Yes, Bruce Alberts, “as it turns out, we can walk and we can talk because the chemistry that makes life possible is much more elaborate and sophisticated than anything we students had ever considered." We have tended to “vastly underestimate the sophistication of many of these remarkable devices."
The closer they look, the more wondrous the cell gets. Who would have thought that the requirement to make these fatty acids would require machinery with moving parts and reaction chambers? Who would have imagined their surfaces would be covered with complex proteins that regulate the production inside? Who would have realized that fat was so important, the cell had complex assembly plants to build it? Fat is almost a mild cussword in our vocabulary, but it is another class of molecular building blocks we couldn’t live without. Fats, sugars, proteins and nucleic acids all work together in life, from humans to lowly fungi. Each class of molecules has immense variety, each is essential, and each is manufactured to spec by precision machinery. What a wonderful post-Darwinian world.
How do origin of life researchers envision the arise of these hyper complex nano factories and assembly lines to make fatty acids ? The scientific paper The lipid world says :
Self-assembly of amphiphilic molecules into complex supramolecular structures is spontaneous. The plausibility that such structures were present in the prebiotic environment is supported by the occurrence of amphiphilic molecules in carbonaceous meteorites and the demonstration that they can assemble into membrane vesicles.
This paper shows the helplessness of proponents of natural prebiotic origin of lipids. Its a hudge gap between above explanation, and the arise of hypercomplex multyenzymatic proteins, which produce fatty acids through advanced, regulated, precise, coordinated multistep factory assembly-line like robotic procedures.
I conclude that the make of essential fatty acids, ingredients of cell membranes, requires interdependent irreducible complex procedures, several different metabolic pathways in order to make the substrates and produce the energy used in the process, several enzymes, the whole machinery to make the assembly proteins and enzymes. Since this constitutes a complex interlocked process, it could not be due to step by step evolutionary manner. Fatty acids, constituents of the cell membranes, had to exist right from the start for life to arise. This fact makes the design inference the most rational one.
Looked at that link
evidence of God, a rational belief this forum has the goal to organize and unite information and compelling evidence for the existence of the God of the bibleCan you do more than cut and paste? PS. Have you ever tried to look at the Bible as an incredible work of self-worship rather than a guide to some unknowable god. Which brings up an interesting point I've always been curious about. I've read in the Bible that God is beyond our comprehension - why is that lesson ignored? Why can't you appreciate (and be at peace with) your vision of god as your personal vision of god and NOT some universal absolute? Sort of like the Bible being a 'Shadow Play', that helps give a sense of god, but no more than that. Any god people out there that want to do more than posterbation, your thoughts will be welcome.
We cannot fully comprehend God, but he has given us some comprehension of his character and attributes.
We cannot fully comprehend God, but he has given us some comprehension of his character and attributes.How do you know it came from him and not from a group of ordinary humans fantasizing?
We cannot fully comprehend God, but he has given us some comprehension of his character and attributes.How do you know it came from him and not from a group of ordinary humans fantasizing? I have found support of my world view and faith in the God of the bible through personal experience, theology, philosophy, and science.