Feast and Famine Flashcards
Principal of Energy Homeostasis
Serum glucose concentration remains constant, everything else varies
3 ways metabolic pathways are regulated
- allosteric effectors
- covalent modification
- changes in amounts of key enzymes
Acetyl-CoA Signals and Affects
Signals: availability of acetyl-CoA
Affects: activates pyruvate carboxylase (GNG), inhibits pyruvate decarboxylase
AMP Signals and Affects
Signals: low energy charge
Affects: activates glycogen phosphorylase and PFK1
Citrate Signals and Affects
Signals: Availability of acetyl-CoA
Affects: activates acetyl-CoA carboxylase (FA synthesis), inhibits PFK1 and PFK2 (glycolysis)
Fructose-2,6-Bisphosphate Signals and Affects
Signals: Availability of Glucose
Affects: Activates PFK1 and inhibits F-1,6-Bisphosphatase
Fructose-1,6-Bisphosphate Signals and Affects
Singals: Availability of glucose
Affects: activates pyruvate kinase
Glucose Signals and Affects
Signals: availability of glucose
Affects: activates glucokinase
Malonyl-CoA Signals and Affects
Signals: FA synthesis
Affects: Inhibits CPT1 (FA degradation)
AMP Signals and Affects
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
cAMP Signals and Affects
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
Fatty Acids Signals and Affects
Signals: Starvation (lipolysis)
Affects: induce genes for FA oxidation and ketone synthesis via peroxisome proliferation response element (PPRE)
Glucagon Signals and Affects
Signals: Starvation
Affects: Induces genes for GNG via CREB binding element, represses genes for lipid synthesis via CRE
Insulin Signals and Affects
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)
Characteristics of FA’s as Fuel Source
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
Characteristics of Glucose as Fuel Source
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
Characteristics of AA’s as Fuel Source
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
RBC’s Fuel source
glucose —> lactate
Muscles Fuel Source
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
Heart Energy Considerations and Fuel Preference
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
Brain Energy Considerations and Preferences
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
Adipose Tissue Fuel Storage
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
Liver Considerations and Fuel Preference
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
Objectives of Well-Fed State
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
Early Fast Adaptations Made
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
Late Fast/Starvation Adaptations
- -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
Refeeding Syndrome: 2 Considerations
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
Fuel Consumption During Exercise
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
Skeletal Muscle In Well-Fed, Early/Late Fast
[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
Heart Muscle in Well-Fed, Early/Late Fast
[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
Brain in Well-Fed, Early/Late Fast
[Energy Source] Well-Fed: Glucose; Early-Fast: glucose; Late-Fast: ketone bodies > glucose
[Calorie Storage and Export] N/A for all
Adipose Tissue in Well-Fed, Early/Late Fast
[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
Liver in Well-Fed, Early/Late Fast
[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
