Download Biochemistry Objectives 42

Biochemistry Objectives 42
1.
Epinephrine biosynthesis:
a.
Products and cofactors of:
a. Tyrosine hydroxylase: catalyzes conversion of tyrosine to L-dopa
using BH4 as a cofactor
b. DOPA decarboxylase: catalyzes conversion of L-dopa to dopamine
using pyridoxal phosphate as a cofactor
c. Dopamine hydroxylase: catalyzes conversion of dopamine to
norepinephrine using ascorbate and copper as cofactors
d. PNMT: catalyzes conversion of norepinephrine to epinephrine using
SAM to methylate norepinephrine
b.
Rate-determining enzyme and regulation mechanism: tyrosine
hydroxylase; activated by acetylcholine and Gs induced cAMP increase,
inhibited by catecholamine feedback inhibition.
c.
Acetylcholine and catecholamine release: acetylcholine causes target cell
depolarization, increased Ca2+ influx, and subsequent catecholamine
vesicular fusion to release catecholamine into the circulation.
d.
Glucocorticoid and epinephrine biosynthesis: glucocorticoids are released
by the intra-adrenal portal system to induce PNMT activity
 Note: epinephrine, norepinephrine, and dopamine are broken down by
MAO and COMT. Epinephrine and norepinephrine produce
vanillylmandelic acid, whereas dopamine forms homovanillic acid.
2.
Adrenergic receptors:
a.
-adrenergic receptor structure: a Gs receptor characterized by an
extracellular N-terminus, 7 transmembrane domains, and an intracellular
C-terminus with Gs-protein binding ability
b.
Adrenergic subtypes and second messengers:
a. 1: Gq, IP3/DAG, Ca2+
b. 2: Gi, decreased cAMP
c. 1: Gs, increased cAMP
d. 2: Gs, increased cAMP
c.
Carbohydrate metabolism:
a. 1: increases liver glycogenolysis
b. 2: increases liver/muscle glycogenolysis, liver gluconeogenesis, and
decreases glycogenolysis
d.
Fat metabolism:
a. 2: decreases lipolysis
b. 1: increases lipolysis
e.
2 and 2 receptors and control of pancreatic  cells and juxtaglomerular
cells: 2 (adenylyl cyclase inhibitory) and 2 (adenylyl cyclase excitatory)
receptors have opposing effects. 2 receptors are more abundant, but 2
receptors are more sensitive to epinephrine stimulation. High epinephrine
concentrations, therefore, cause cAMP levels to decrease, while low
epinephrine concentrations cause a cAMP levels to increase.
3.
-adrenergic termination:
a.
GTPase of s: terminates Gs activity and direct downstream signal of adrenergic receptor
b.
-adrenergic receptor kinase (ARK): phosphorylates serine and
threonine residues to reduce -adrenergic receptor activity
c.
-arrestin: binds phosphorylated -adrenergic receptor to inactivate it
d.
Phosphodiesterase: cleaves cAMP to AMP, terminating direct
downstream signal of Gs
e.
Protein phosphatase-1: cleaves PKA-phosphorylated protein products
downstream of cAMP activity to completely terminate products of adrenergic receptor stimulation