1. Random Sequence Difficulties. GOTO Metabolic Pathways require all proteins on any given pathway to make a simultaneous first appearance in working condition. This is because natural selection cannot distinguish between good and bad proteins whenever any along the path are bad. This precludes a gradual step-by-step first appearance. I.e., if all of the proteins are bad to start with, natural selection would not be able to recognize that a particular one had become good while any of the others were still bad.
Also, it is shown that even with assumptions favoring abiogenesis unrealistically, most proteins used in cellular functions would still not have shown up a single time on any planet in the universe for even an hour in over a Googol years. A Googol is 10100. (10100 = 10,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,
000,000,000,000,000,000,000,000,000). This is a very long time. The universe is reputedly only 15,000,000,000 years old.
For all practical purposes, this makes a natural origin of life is impossible. The chemicals of life are simply too complicated. Natural processes form many alternatives, life needs something specific, and there is nothing to constrain natural processes to give those required for life. GOTO