A) Compare and contrast the activities of AMP-dependent protein kinase and cAMP

Question

A) Compare and contrast the activities of AMP-dependent protein kinase and cAMP dependent protein kinase. First of all, give the general functions of cAMP dependent protein kinase (PKA) and AMP activated protein kinase (AMPK).

i) Describe the reactions catalyzed by these enzymes, the overall functions of PKA and AMPK and the allosteric activators and inhibitors of these enzymes. Explain why do these allosteric regulators make sense?    

ii)What are the hormones that lead to stimulation and inhibition of these enzymes and relate to the overall functions of these hormones on body.

iii)What are the biochemical targets and effects of these two enzymes in heart, skeletal muscle, liver, heart and adipose? Include detail including overall functions, metabolic pathways, etc. Details required

Explanation / Answer

AMP-dependent protein kinase and cAMP dependent protein kinase, BOTH OF THEM are very important for the bodies normal functions, they are used a enzymes and their activities influences a lot of other function throughout the body.

cAMP dependent protein kinase also known as protein kinase A is generally functions as regulatory like glycogen, sugar and lipid metabolism.

i) reactions by PKA and AMPK-

Overall function of PKA (also known as cAMP-dependent enzyme) -regulatory like glycogen, sugar and lipid metabolism, work on phosphorylation and de-phosphorylation, helps n activating G-protein couples receptors etc.

AMPK - AMP-dependent protein kinase generally functions as  cellular energy homeostatic molecule, this is also helpful in stimulation of hepatic fatty acid oxidation, ketogenesis, fatty acid oxidation and glucose uptake, cholesterol is also inhibited, and modulation of insulin secretion by pancreatic beta-cells.

PKA, AMPK- allosteric activator and inhibitors-

PKA activation- IN a sequential reaction- cytosolic cAMP increases- two cAMP binds to PKA regulatory subunit- then it detaches itself from the active site- free catalytic site binds with proteins to phosphorylate Ser or Thr residues.

PKA inhibition- A feedback inhibitor using phosphodiesterase, which is one of the substrates activated by the kinase, it converts the active cAMP to AMP.

AMPK is regulated allosterically also post-translationally. This molecule known as AMPK is regulated allosterically by competitive binding on its gamma subunit between ATP and AMP or ADP.

AMPK is inhibited by insulin, leptin, also by inducing various other phosphorylation’s.

ii) Enzymes lead to stimulation and inhibition of these enzymes -

In case of PKA it is regulated and supported by the hormones such as glucagon and epinephrine begin the activation cascade by binding to a G protein–coupled receptor on the target cell.

In general Glucagon is used to treat blood sugar levels in the body, beta blocker overdose, on the other hand epinephrine is also acts as neurotransmitter and it increases blood sugar levels, blood flow of muscles, pupil dilatation etc.

AMPK is regulated by the enzymes known as insulin, leptin, and diacylglycerol by inducing various other phosphorylation’s.

Insulin in general functions as modulator of hyperglycemia, it controls the level of sugar in blood, leptin acts as satiety hormone, made by adipose tissues of the body help in regulation of energy balance by inhibiting hunger.

iii) PKA, AMPK functions-

PKA , 1. It help in glucose metabolism, it has specific and distinct function it a regulatory molecule which is the step from fructose to glucose conversion,

2. PKA is important for the brain as well PKA catalytic subunit encoding gene,

3. In skeletal muscle we have their specific function, Ca2+ release channel, which is functionally important for the muscle cells to function,

4. This has got its specific function in adipocytes and hepatocytes- This helps in G-protein coupling and function.

AMPK- 1. It phosphorylates acetyl-CoA carboxylase 1 also known as sterol regulatory element,

2. It inhibits cholesterol synthesis, triglycerides, so that is helpful for the adipose tissues, and this enzyme activates fatty acid uptake and -oxidation for adipose tissues again.

3. Glucose uptake in skeletal muscle by phosphorylating it Rab-GTPase-activating protein TBC1D1,

4. Helps in intensive protein biosynthesis, it helps in cap-dependent,

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