Feast and Famine

Question 1

Principal of Energy Homeostasis

Answer 1

Serum glucose concentration remains constant, everything else varies

Question 2

3 ways metabolic pathways are regulated

Answer 2

1. allosteric effectors
2. covalent modification
3. changes in amounts of key enzymes

Question 3

Acetyl-CoA Signals and Affects

Answer 3

Signals: availability of acetyl-CoA
Affects: activates pyruvate carboxylase (GNG), inhibits pyruvate decarboxylase

Question 4

AMP Signals and Affects

Answer 4

Signals: low energy charge
Affects: activates glycogen phosphorylase and PFK1

Question 5

Citrate Signals and Affects

Answer 5

Signals: Availability of acetyl-CoA
Affects: activates acetyl-CoA carboxylase (FA synthesis), inhibits PFK1 and PFK2 (glycolysis)

Question 6

Fructose-2,6-Bisphosphate Signals and Affects

Answer 6

Signals: Availability of Glucose
Affects: Activates PFK1 and inhibits F-1,6-Bisphosphatase

Question 7

Fructose-1,6-Bisphosphate Signals and Affects

Answer 7

Singals: Availability of glucose
Affects: activates pyruvate kinase

Question 8

Glucose Signals and Affects

Answer 8

Signals: availability of glucose
Affects: activates glucokinase

Question 9

Malonyl-CoA Signals and Affects

Answer 9

Signals: FA synthesis
Affects: Inhibits CPT1 (FA degradation)

Question 10

AMP Signals and Affects

Answer 10

Signals: low energy charge
Affects: Activates AMP dependant kinase (AMPK), which leads to phosphorylation of key enzymes: Inhibits GNG, protein synthesis, lipogenesis, and cholesterol synthesis

Question 11

cAMP Signals and Affects

Answer 11

Signals: Starvation–low glucose
Affects: Activates protein kinase A (PKA), which leads to phosphorylation of key enzymes: increase in glycogenolysis and GNG; inhibits glycolysis and lipogenesis

Question 12

Fatty Acids Signals and Affects

Answer 12

Signals: Starvation (lipolysis)
Affects: induce genes for FA oxidation and ketone synthesis via peroxisome proliferation response element (PPRE)

Question 13

Glucagon Signals and Affects

Answer 13

Signals: Starvation
Affects: Induces genes for GNG via CREB binding element, represses genes for lipid synthesis via CRE

Question 14

Insulin Signals and Affects

Answer 14

Signals: Well-fed state
Affects: induces genes for lipid synthesis via SREBP-1c responsive element, represses genes for GNG and FA oxidation via insulin response element (IRE)

Question 15

Characteristics of FA’s as Fuel Source

Answer 15

high energy content; endless amounts; requires oxygen so cannot be used for short, anaerobic bursts; cannot cross blood:brain barrier; bulk of them (acetyl-CoA) cannot be converted to glucose

Question 16

Characteristics of Glucose as Fuel Source

Answer 16

less energy than FA’s; catabolized quickly w/o oxygen (muscles produce lactate); can cross blood:brain barrier; glucose stores are relatively small; body must devote lot of attention to regulation of glucose breakdown, storage and synthesis

Question 17

Characteristics of AA’s as Fuel Source

Answer 17

available in large amounts after meal but no storage mechanism; instead AA’s are either incorporated into proteins or broken down immediately; one important role in energy homeostasis = some of them can be converted to glucose during starvation

Question 18

RBC’s Fuel source

Answer 18

glucose —> lactate

Question 19

Muscles Fuel Source

Answer 19

prefer FA’s for energy but can also use ketone bodies and glucose or their own glycogen stores; muscles have AA reserves but those must be converted to glucose in liver

Question 20

Heart Energy Considerations and Fuel Preference

Answer 20

heart requires constant supply of energy, heart doesnt store energy, heart cannot function anaerobically (no lactate production to avoid damage to heart muscle cells), heart has special lactate dehydrogenase enzyme isoform which favors conversion of lactate into pyruvate and allows heart to metabolize lactate for energy; heart prefers FA’s for energy due to higher energy content but can also use glucose, lactate, and ketone bodies

Question 21

Brain Energy Considerations and Preferences

Answer 21

brain needs constant energy supply consuming 20% of available glucose, no glycogen or fat stores; brains CANNOT use FA’s so totally dependent on glucose; severe starvation brain can use ketone bodies for a bit

Question 22

Adipose Tissue Fuel Storage

Answer 22

functions mainly as storage for metabolic energy; converts glucose to TAG’s in well-fed and exports TAG’s in starvation; in times of need, TAG’s broken down to glycerol and FA’s by HSL to supply heart w/ energy

Question 23

Liver Considerations and Fuel Preference

Answer 23

capable of using, storing, converting and exporting jsut about everything; has high energy need so it uses all available sources; stores glycogen but NOT fat; in well-fed state, liver converts glucose into TAG’s for export in VLDL particles and storage in adipose and in starvation it converts AAs and FAs into glucose and ketone bodies

Question 24

Objectives of Well-Fed State

Answer 24

Overall: Nutrients removed from circulation and put into storage

• -glucose stored in liver/muscles and excess glucose converted into VLDL by liver for storage in adipose tissue
• -AA’s used for protein synthesis and excess are converted to glucose/FA’s by liver
• -Dietary TAG’s (chylomicrons) broken down for energy by most cells of body

Question 25

Early Fast Adaptations Made

Answer 25

Liver releases glucose from glycogen stores

• -FA’s/glycerol released from adipose for muscle cells
• -ketone bodies produced by liver
• -AA’s from protein breakdown are released from muscles and liver converts them to glucose and ketone bodies
• -will be rise in ammonia from protein degradation for urea cycle enzymes induced

Question 26

Late Fast/Starvation Adaptations

Answer 26

• -liver glycogen is fully depleted so all glucose consumed is from breakdown of muscle protein and storage fat
• -kidney aids liver in making ketone bodies from FA’s
• -breakdown of muscle protein slows down due to reduced demand for glucose
• -overall, basal metabolic rate slows down as well (ensures the brain has sufficient energy even if all glycogen stores are spent)
• • Brain will begin to use ketone bodies

Question 27

Refeeding Syndrome: 2 Considerations

Answer 27

1) severely starved patients lack digestive enzymes–body protein degradation to produce glucose from GNG—w/o digestive enzymes patient cannot breakdown dietary carbs and fats–oral feeding = diarrhea b/c it supports growth of intestinal microorganism
2) intracellular phosphate stores are depleted—shift from carb metabolism to GNG/ketogenesis depletes -P stores—reintroduction of carbs start glycolysis (requires -P’s) and this depletes -P pool further—all glycolytically active cells soak up all -P’s from serum which leads to hypophosphatemia which is life-threatening ALWAYS WATCH ELECTROLYTES DURING REFEEDING of a patient

Question 28

Fuel Consumption During Exercise

Answer 28

first 20 seconds, muscles driven by creatine/ATP reserves

• -moderate exercise uses half FA oxidation and half glycogen/glucose metabolism
• -after an hour of vigorous exercise, glycogen stores are 50% gone so more FA’s used
• -after 2 hours of vigorous exercise, all glycogen stores are gone and energy comes exclusively from FA oxidation

Question 29

Skeletal Muscle In Well-Fed, Early/Late Fast

Answer 29

[Energy Source] Well-Fed: FA’s and glucose; Early Fast: Glycogen, FA’s and ketone bodies; Late Fast: FA’s
[Calorie Storage] Well-Fed: Glycogen; Early/Late Fast: N/A
[Calorie Export] Well-Fed: Lactate, Alanine, Glutamine; Early Fast: Lactate, Alanine, Glutamine, AA’s; Late Fast: AA’s

Question 30

Heart Muscle in Well-Fed, Early/Late Fast

Answer 30

[Energy Source] Well-Fed: FA’s > glucose/lactate; Early-Fast: FA’s > glucose/lactate; Late-Fast: Ketone Bodies > glucose/lactate
[Calorie Storage] Well-Fed: Glycogen (very little); Early/Late Fast: N/A
[Calorie Export] N/A for all stages

Question 31

Brain in Well-Fed, Early/Late Fast

Answer 31

[Energy Source] Well-Fed: Glucose; Early-Fast: glucose; Late-Fast: ketone bodies > glucose
[Calorie Storage and Export] N/A for all

Question 32

Adipose Tissue in Well-Fed, Early/Late Fast

Answer 32

[Energy Source] Well-Fed, Early and Late Fast: Glucose
[Calorie Storage] Well-Fed: TAG’s; Early/Late-Fast: N/A
[Calorie Export] Well-Fed: N/A; Early/Late-Fast: FA’s and glycerol

Question 33

Liver in Well-Fed, Early/Late Fast

Answer 33

[Energy Source] Well-Fed: FA’s, glucose, AA’s, Lactate; Early Fast: FA’s and AA’s; Late-Fast: FA’s
[Calorie Storage] Well-fed: glycogen; Early/Late-Fast: N/A
[Calorie Export] Well-Fed: VLDL; Early-Fast: Glucose and ketone bodies; Late-Fast: glucose and ketone bodies