What is the ultimate source of ADP/ATP in humans?

Question

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

Answer 1

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.

Answer 2

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.

3. 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?

4. 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
   

5. 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.