Metabolism and Starvation

Question 1

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

Answer 1

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

Question 2

where does gluconeogenesis occur?

Answer 2

in the kidney and liver

Question 3

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

Answer 3

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

Question 4

where does the liver and the 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 which begins with ingestion and continues until nutrients are assimilated, utilized, and stored

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

Question 6

what causes the transition between the metabolic cycle phases?

Answer 6

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

Question 7

what is the difference between short and long term regulation?

Answer 7

short term: phosphorylation and covalent modification of enzymes

long term: 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, the AMPK senses AMP as a sign of low energy and it causes increased FA oxidation and increased cellular glucose uptake, there is decreased FA synthesis and decreased cell division as 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 levels increase, which leads to increased insulin and decreased glucagon and epinephrine

Question 10

where are glucagon and insulin secreted?

Answer 10

pancreatic islets.

glucagon is made by alpha cells on border

insulin is made by beta cells in the center

Question 11

in what form is insulin synthesized and released?

Answer 11

it is synthesized as a preprohormone, the presequence at N terminal directs it into the ER where it is removed and the pro sequence directs proper folding and is removed by proteases in the secretory vesicle

Question 12

what are other regulators of insulin?

Answer 12

fatty acids, ketones, amino acids, paracrine signals from alpha and delta cells, parasympathetic and sympathetic stimulation

Question 13

what is the second most important insulin stimuli?

Answer 13

glucagon-like peptide-1, GLP-1, which is 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 alpha cells from inhibition, 2. hypothalamus is glucose sensitive, and falling levels release epinephrine, which stimulates glucagon release

Question 15

insulin, glucagon, and epinephrine receptors are located where?

Answer 15

extracellularly

Question 16

describe the downstream effects of glucagon and epinephrine

Answer 16

these effect cAMP, adenylate cyclase is activated by the alpha subunit of a G protein which generates cAMP. cAMP activates PKA, which activates glycogen breakdown and activates lipolysis and activates FA utilization which activates gluconeogenesis and 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

insulin activates tyrosine kinase complex which autophosphorylates and activates proteins with SH2 domains, eventually activating Akt. this has 2 effects: 1) antagonizes cAMP effects inhibiting gluconeogenesis, inhibiting lipolysis, and inhibiting ketogenesis 2) increases GLUT-4 (glucose transporter)

Question 18

what are the enzymatic targets for liberating glucose from glycogen?

Answer 18

activation of glycogen phosphorylase and inactivation of glycogen synthase

Question 19

what are enzymatic targets for activating gluconeogenesis?

Answer 19

1) increased precursors 2) altered enzymes decreased PFK-2, decreased pyruvate kinase, increased PEPCK and increased G6Pase

Question 20

what are the enzymatic targets for activating adipose tissue lipolysis?

Answer 20

phosphorylation of HSL and perilipin which activates HSL and ATGL

Question 21

what are the enzymatic targets for activating FA oxidation and ketogenesis?

Answer 21

decrease in the ACC enzyme, which lowers malonyl-CoA levels, which releases inhibition of CPT-1, which allow FAs to enter the mitochondria for oxiation