Abstract Uncertainties persist as to how human metabolism may adapt to or accommodate lower intakes of some individual amino acids when compared to the set of amino acid and protein requirements, even when considering the theoretically simple criteria related to protein homeostasis. Amino acid metabolism is a much more dynamic and complex process that is still only assessed from fragmented information. Nonetheless, based on our current knowledge, proteins from plant sources are wholly adequate nutritionally in healthy adults, even if animal proteins are excluded, provided they are mixed and form part of a varied, good quality diet. This might not be the case in some elderly people, but this remains a research question that requires studies to assess the final functional impact. When plant protein sources are not mixed and mostly consist of cereals, in a diet associated with a low protein and energy intake, as in some developing countries, a low lysine intake remains a concern whose impact needs to be further characterized. More generally, the effect of plant/animal protein intake on the background metabolism of amino acids remains largely unexplored, even though this is expected to be the rationale regarding the impact of dietary protein sources on numerous functions and health outcomes. In Western countries, the standard view and classical concepts underlying “protein quality” are outdated. We need more direct study on the impact of plant and animal protein sources on metabolic pathways and final physiological endpoints.