Metabolic Homeostasis #23 Flashcards
the function of AMP-dependent protein Kinase (AMPK)
activates ATP -generating processes
inhibits ATP- consuming processes
Structure of AMPK
is an alpha-beta-gamma heterotrimer
the alpha contains Ser/Thr172 protein kinase domain
the gamma contains sites for allosteric activation by AMP or inhibition by ATP
when is AMPK activated?
when it is phosphorylated
the major AMPK in the body is
the liver kinase LKB1
adenylate kinase perfoms?
2ADP–>
AMPK function in the heart
it affects the PFK-2/FBPase-2 enzymes that affect F2,6P concentration.
AMPK inhibits which 3 reactions in the liver
lipogenesis
gluconeogenesis
glycogen synthesis
how does AMPK dependent phosphorylation inhibit FA biosynthesis
by stopping acetyl-coA carboxylase
how does AMPK dependent phosphorylation inhibit cholesterol biosynthesis
by stopping HMG-coA reductase
how does AMPK dependent phosphorylation inhibit glycogen synthesis
by stopping glycogen synthase
AMPK promotes which 2 processes in skeletal muscle?
FA oxidation
Glucose uptake
how does AMPK promote FA oxidation
AMPK inhibits acetyl-coA carboxylase. This means a decrease in malonyl-coA. This means an increase in activity of carnitine acyltransferase 1. Therefore an increase in acyl-coA entry into mitochondria
how does AMPK increase glucose uptake in skeletal muscle?
by increasing expression of GLUT4, thus facilitating insulin independent entry of glucose into cells
how does AMPK dependent phosphorylation inhibit lipolysis in adipocytes
it phosphorylate hormone sensitive lipase in adipose tissue, this inhibits the lipase. Therefore less TAG are broken into FA. Thus a decrease of FA in bloodstream. This help prevent buildup of intracellular free FA –> soapy
how does adiponectin affect AMPK
it is a protein hormone synthesized by adipocytes.
it shows in the blood stream as homotrimers LMW, homoexmers MMW, aggregates HMW, and proteolytic fragments.
When it binds to its receptors on the liver and muscle cells it stimulates the phosphorylation of AMPK. Thus acting to increase insulin sensitivity
decreased adiponectin is associated with
insulin resistance. This is because adiponectin increases insulin sensitivity
why does the blood concentration of adiponectin decrease with increases adipose tissue?
because of increases production of tumor necrosis factor alpha, which is a growth factor that decreases expression and secretion of adiponectin from adipocytes
leptin
is a protein hormone, synthesized and secreted by adipose cells, it decreases appetite. It is called the satiety hormone. encoded by OB gene in mice
neuropeptide Y
is synthesized and releases in the hypothalamus, it increases appetite
how is NY secretion inhibited?
by insulin and leptin binding on hypothalamus
in obese humans leptin ….
leptin resistance is present, thus increases levels are associated with high fat levels.
ghrelin
is an appetite stimulating peptide secreted by an empty stomach
PYY
is an appetite suppressing hormone released by GI tract
when glucose levels are low, how do muscle cells get their energy fill?
by switching to FA metabolism
the livers reserve of glycogen is exhausted after how many hours?
in 40 hrs
after glycogen is exhausted how does the body get glucose?
by gluconeogenesis
diabetes type 1
lack/functional deficiencies of pancreatic B cells
what 2 substances increase AMPK activity
metformin and thiazolidinediones, they inhibit gluconeogenesis in liver and increase glucose uptake by muscle. they increase AMP/ATP ratio and decrease insulin resistance by activating peroxisome proliferator activated receptor-Y. Which induces synthesis of adiponectin and activation of AMPK. this causes decreased lipolysis and FA export–> decreased insulin resistance
restinin in mice
blocks the action of insulin on adipocytes
