Lipase switch-on

The second mark — made on the droplet surface, and the one that actually starts the cutting.

Lipase docking increases it.

The second lipase is switched on in two separate steps, not one — and most evidence only ever shows one of them. 'HSL is phosphorylated by PKA at Ser660, triggering its translocation to lipid droplets; it then forms a stable association with lipid droplets. The subsequent phosphorylation of HSL Ser563 on the surface of the lipid droplets promotes the intrinsic catalytic activity of the lipase' (doi 10.1371/journal.pone.0100559 (PMC4064000) — PRIP Regulates Lipolysis by Modulating the Phosphorylation of Hormone-Sensitive Lipase). ⇒ one mark gets the enzyme to the fat. A different mark turns it on once it is there. This is why 'it raises the active form of the lipase' is an incomplete claim unless the site is named. An ingredient that marks only the switch-on residue is relying on the enzyme having already arrived by other means. And a good deal of it has: 'up to 50% of cellular HSL is LD-associated in the basal state' (PMID 16595669 — Perilipin promotes hormone-sensitive lipase-mediated adipocyte lipolysis via phosphorylation-dependent and -independent mechanisms) — half the lipase is already parked at the droplet before any signal arrives. doi 10.1371/journal.pone.0100559 · PMID 16595669 · PMC4064000

Fat droplet coating reduces it.

The coat is not the door — it is permission to work once inside. This was settled by removing every mark site from the coat protein and watching what still happened: 'PKA-induced HSL translocation was independent of perilipin phosphorylation. However, [the mutant] failed to enhance PKA-stimulated lipolysis... Thus, the lipolytic action(S) of HSL at the LD surface requires PKA-dependent perilipin phosphorylation' (PMID 16595669 — Perilipin promotes hormone-sensitive lipase-mediated adipocyte lipolysis via phosphorylation-dependent and -independent mechanisms). ⇒ the lipase still arrives without the coat being marked. It simply cannot do anything when it gets there. That is a sharper and more useful statement than the usual one about the coat 'blocking access'. PMID 16595669

Lipolysis signal increases it.

The switch-on step, and the species trap underneath it. Almost all published site numbers come from rodent studies, and the numbering does not carry across: 'in vitro phosphorylation of human HSL by PKA occurs primarily on Ser649 and Ser650 (Ser659 and Ser660 in rat HSL)' (doi 10.1371/journal.pone.0003756 (pmc2582450) — Ser649 and Ser650 Are the Major Determinants of PKA-Mediated Activation of human Hormone-Sensitive Lipase). ⇒ a residue number quoted from a mouse experiment is not the same residue in a person, and the major human site is not the one most often quoted. This does not make the animal work wrong — it means the site-level precision it offers does not transfer without translation. doi 10.1371/journal.pone.0003756

It increases Fat-releasing enzyme (HSL).

The switch-on step, and the species trap underneath it. Almost all published site numbers come from rodent studies, and the numbering does not carry across: 'in vitro phosphorylation of human HSL by PKA occurs primarily on Ser649 and Ser650 (Ser659 and Ser660 in rat HSL)' (doi 10.1371/journal.pone.0003756 (pmc2582450) — Ser649 and Ser650 Are the Major Determinants of PKA-Mediated Activation of human Hormone-Sensitive Lipase). ⇒ a residue number quoted from a mouse experiment is not the same residue in a person, and the major human site is not the one most often quoted. This does not make the animal work wrong — it means the site-level precision it offers does not transfer without translation. doi 10.1371/journal.pone.0003756

Lipolytic (Stored-Fat Mobilization) →