Metabolism and Starvation

Question 1

what are the precursors for gluconeogenesis and does the body get them?

Answer 1

lactate- anaerobic glycolysis
glycerol- fatty acid breakdown
amino acids- muscle breakdown

Question 2

where does gluceoneogenesis occur?

Answer 2

kidney and liver

Question 3

how much energy from glycogen is stored in the body? how much can defend blood glucose?

Answer 3

2000 total, only 300-400 is in the liver for defense

Question 4

where does the liver and kidney get the energy for gluconeogenesis?

Answer 4

fatty acid oxidation

Question 5

what are the two phases of the metabolic cycle?

Answer 5

anabolic (fed) phase- begins with ingestion and coninues until nutrients are assimilated, utilized, and stored

catabolic (fasting) phase- begins at termination of anabolic phase and continues until next meal. this is the phase when reserves are used

Question 6

what causes the transition between the metabolic cycle phases?

Answer 6

rises in insulin are associated with anabolic whereas a drop in insulin is associated with catabolism

Question 7

difference between short and long term regulation

Answer 7

short- phosphorylation and covalent modificication of enzymes

long- changes in the enzyme/protein count in the cells, usually via genetic modification

Question 8

describe regulation via AMP-activated protein kinase (AMPK)

Answer 8

decreased blood glucose = decreased ATP = adenylate kinase converting ADP into ATP and AMP.

AMPK senses AMP as “low energy”. it causes

increased fatty acid oxidation
increased cellular glucose uptake
decreased fatty acid synthesis
decreased cell division

it is inhibited by ATP

Question 9

what is the most important factor in how insulin, glucagon, and epinephrine are regulated?

Answer 9

blood glucose level

increased BGL = increased insulin, decreased glucagon and epinephrine

Question 10

where are glucagon and insulin secreted?

Answer 10

pancreatic islets.

glucagon- a cells on border
insulin- b cells in center

Question 11

in what form is insulin synthesized and released

Answer 11

synthesized as a preprohormone.

pre sequence at N terminal directs it into the ER where it is removed
pro sequence directs proper folding and is removed by proteases in secretory vesicle

Question 12

list other regulators of insulin

Answer 12

fatty acids
ketones
amino acids
paracrine signaling from a and d cells
parasympathetic
sympathetic

Question 13

what is the second most important insulin stimuli?

Answer 13

glucagon-like peptide-1 GLP-1.

synthesized and secreted in the small intestine after a carb meal

Question 14

how is glucagon release triggered?

Answer 14

1. as glucose levels fall, insulin secretion falls, releasing a cells from inhibition
2. hypothalamus is glucose sensitive, and falling levels release epinephrine, which stimulates glucagon release

Question 15

insulin, glucagon, and epinphrine receptors are all extracellular

Answer 15

ok

Question 16

describe the downstream effects of glucagon and epinephrine

Answer 16

they effect cAMP.

adenylate cyclase is activated by the a-subunit of a G-protein and generates cAMP. cAMP activates PKA which:

activates glycogen breakdown
activates lypolysis
activates fatty acid utilization
activates gluconeogenesis
activates ketone synthesis

PKA levels are also effected by cAMP phosphodiesterase (PDE), which breaks down cAMP.

Question 17

describe the downstream effects of insulin

Answer 17

activates a tyrosine kinase complex which autophosphorylates and activates proteins with SH2 domains, eventually activating Akt. this has 2 effects:

1. antagonize cAMP effects
activate glycogen synthase
inhibit gluconeogenesis
inhibit lipolysis
inhibit ketogensis

2. increase GLUT-4 (glucose transporter)

Question 18

enzymatic targets for liberating glucose from glycogen

Answer 18

activation of glycogen phosphorylase and inactivation of glycogen synthase

Question 19

enzymatic targets for activating gluconeogenesis

Answer 19

1. increased precursors
2. altered enzymes
   - decreased PFK-2
   - decreased pyruvate kinase
   - increased PEP-carboxykinase
   - increased glucose-6-phosphatase

Question 20

enzymatic targets for activating adipose tissue lipolysis

Answer 20

phosphorylation of HSL and perilipin which actviates HSL and ATGL

Question 21

enzymatic targets for activating FA oxidation and ketogenesis

Answer 21

PKA would decrease ACC enzyme, which lowers malonyl-CoA levels, which releases its inhibition of CPT-1, allowing FAs into the mitochondria for oxidation (and ketogenesis in the liver)

in the liver, this inhibition also prevents new fatty acid synthesis