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I am teaching myself Cell Biology from the internet. Despite my usually good Googling skills, I'm stuck in a loop with this question.

Q: What is the source of ATP?

A: ADP

Q: What is the source of ADP?

A: ATP

At first I thought that ATP synthase actually created ATP from scratch as intimated here:

ATP synthase is an important enzyme that creates the energy storage molecule adenosine triphosphate Wikipedia

I then realise that ATP synthase doesn't create ATP so much as convert ADP.

My Question

Can humans synthesise ADP/ATP from scratch. If so, where are these phosphates made and if not what food source provides them and how? Also, where do we get the phosphorus?

Thanks

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2 Answers 2

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Phosphorus is a very common nutrient, found in high levels in proteins, which are in such foods as milk and milk products, meat, beans, lentils, nuts, and grains, especially whole grains. Phosphorus is found in smaller amounts in vegetables and fruit, as well. Adenosine can be found in many of the same foods, both as free ATP/ADP/AMP, and as part of the DNA found in all animal and plant-based foods (are there any other kinds?).

Adenine (the nucleotide base before the addition of ribose creates adenosine) is synthesized via the purine synthesis pathway, whose ultimate product is IMP, or inosine monophosphate. IMP is then converted to adenylosuccinate, then to AMP, which is then phosphorylated to ATP. It should be noted that, as is the case in most biosynthetic pathways, this one requires ATP to power it along, meaning it takes ATP to make ATP.

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  • $\begingroup$ Would the downvoter care to comment so I can improve my answer? What's wrong with it? $\endgroup$
    – MattDMo
    Oct 25, 2016 at 21:27
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    $\begingroup$ I can't imagine why this was downvoted (+1 from me). Maybe because a quick look at the wiki link obviously requires ADP/ATP in its own production and someone thought it was a circular answer? That's my best guess. $\endgroup$ Oct 26, 2016 at 3:21
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    $\begingroup$ @anongoodnurse The question isn't "Where did the first molecule of ATP come from?", but I guess that's as good a guess as any. I just wish people would leave comments when there's nothing obviously wrong with an answer, like another answer directly contradicting it or something. Oh well, it's not like the rep is a big deal or anything. I just want to be loved! :) $\endgroup$
    – MattDMo
    Oct 26, 2016 at 11:46
  • $\begingroup$ Not my downvote but the only correction I would make is the phosphorous content of grains. They are very rich in phosphate but most of it is locked up in phytate which most mammals can't digest. If you go on a high grain vegetarian diet your phosphorous intake actually decreases. See: ncbi.nlm.nih.gov/pubmed/21183586 $\endgroup$
    – mimat
    Nov 1, 2016 at 11:16
  • $\begingroup$ @mimat Thanks for the feedback. Do you know how much is available from proteins and nucleic acids in whole grains as compared to the other foods I listed? That was kind of what I was getting at, not just the total phosphate levels regardless of bioavailability. Also, is phytate broken down by cooking, such that, for example, whole-grain bread has more bioavailable phosphorus than raw grains? $\endgroup$
    – MattDMo
    Nov 1, 2016 at 17:52
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As the concern expressed by the poster has recurred in an essentially similar question despite the excellent answer by @MattdDMo, I shall provide an additional answer labouring the basic biochemical points.

  1. Inorganic phosphate (the term used to describe the mixture of different phosphate ions present at physiological pH) in animals is derived from the diet.

  2. Biochemical processes exist (substrate-level and oxidative phosphorylation) in which this inorganic phosphate is transferred to adenosine diphosphate (ADP) resulting in adenosine triphosphate (ATP).

This explains how the γ-phosphate (third phosphate) of ATP can derive from inorganic phosphate de novo. It does not explain where the α- and β-phosphates of ADP (and hence ATP) come from.

  1. There is an enzyme, adenylate kinase, that catalyses the formation of ADP from ATP and AMP:

             ATP + AMP ⇔ 2 ADP
    

This can be regarded as transferring the γ-phosphate of ATP (derived from phosphate) to AMP to provide the β-phosphate of one of the two molecules of ADP produced in the reaction. So that explains how the β-phosphate of ADP can derive from inorganic phosphate, and thus how both β- and γ-phosphates of ATP derive from inorganic phosphate de novo. What about the α-phosphate?

  1. The α-phosphate in the purine monophosphate AMP derives from one of its precursors, ribose 5-phosphate. The relative points of the pathway of purine synthesis that can be found in detail in biochemical texts such as Berg et al.:

    ribose-5P →→→→→→ inosine monophosphate →→ AMP
    
  2. And the phosphate in the ribose 5-phosphate derives from the γ-phosphate of ATP in the phosphorylation of glucose in the hexokinase reaction of glycolysis, followed by the reactions of the pentose phosphate pathway. In outline:

    ATP + glucose → ADP + glucose 6-P →→ ribulose 5-P → ribose 5-P 
    

In summary, the incorporation of inorganic phosphate (ultimately maintained by dietary intake) into the γ-phosphate position of ATP enables its incorporation into the α- and β- positions during purine monophosphate synthesis and subsequent reactions.

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