Mammalian Fuel Metabolism Flashcards
Specialization of metabolism in the brain
-high respiration rate
-energy is used to power ATPase that maintains the membrane potential in neurons
-the brain stores very little glycogen so it requires a steady glucose supply
Specialization of metabolism in muscle
storage: glucose is stored as glycogen because it can be broken down quickly.
fasting: glycogen is consumed quickly so fatty acids and ketone bodies are used when glycogen is depleted
Muscle stores ATP as phosphocreatine which is used to replace ATP when its depleted
Anaerobic glycolysis takes over and produces lactate
Eventually oxidative phosphorylation is used to maintain ATP production
Specialization of metabolism in adipose tissue
storage: adipocytes convert free fatty acids to triacylglycrol for energy storage. glycerol is produced from glucose vi DHAP
fasting: adipocytes release FFAs from TAG and export them to the blood. absence of new glycerol drives this process
Adiponectin
produced by adipocytes but production is decreased if there’s too much adipose tissue
binds receptors on muscle and liver cells which stimulates the AMPK pathway, inhibiting gluconeogenesis, and stimulates FA uptake and oxidation
Leptin
produced by fat cells to control appetite and body weight
production increases with increased adipose tissue, but the receptor or transports across BBB may be deficient in obese people
Neuropeptide Y
produced by hypothalamus, stimulates appetite
leptin and insulin prevent secretion
Human ghrelin
stimulates appetite by increasing NPY levels
secreted by empty stomach
Human PYY
-decreases appetite by inhibiting NPY
-secreted from GI tract
Glucokinase
not inhibited by its product (G6P) and is active in high glucose concentrations (high Km)
It allows the liver to take up excess glucose but doesn’t compete with other organs at low blood glucose
4 fates of G6P in the liver
- converted to glucose for secretion
- converted to glycogen for storage
- converted to acetyl-coa for lipid biosynthesis
- generate ribose-5-phosphate and NADPH via PPP
Cori cycle
purpose: recycle lactate
steps:
1. lactate travels to liver from muscle via blood
2. lactate dehydrogenase converts to pyruvate
3. converted to acetyl-coa for lipid biosynthesis
4. new glucose secreted to replenish muscle tissue
Glucose-alanine cycle
Purpose: circulates pyruvate during fasting to produce NH3 and glucose
steps:
1. pyruvate converted to alanine which then travels from muscles to liver
2. amino group transferred to a-ketoglutarate, generating glu
3. Glu releases amino groups as NH3
4. Ala converted to pyruvate and glucose
5. Glucose secreted
Insulin is secreted by _____ in response to high blood glucose levels
pancreatic b-cells
How is glucose uptake in muscle and adipocytes regulated
it’s regulated by insulin through controlling GLUT4 exocytosis
GLUT4
normally in membrane vesicles but insulin stimulates vesicle localization with the plasma membrane for glucose uptake
Does the brain’s rate of glucose uptake rely on insulin
No
What affect does insulin have on the liver
liver represses gluconeogenesis to store glucose
AMP-Dependent-Protein Kinase (AMPK)
-intracellular kinase that responds to the AMP/ATP ratio
AMP allosterically activates while ATP allosterically inhibits
AMPK activates
PRK2/FBPase- increased glycolysis
GLUT4 exocytosis- increased glucose uptake in the muscle
FA Oxidation- decreasing malonyl-coa via acetyl-coa decarboxylase inhibition
AMPK inhibits
acetyl-coa decarboylase
glycogen synthase
Starvation
12 hours
-increased glucagon leads to FA mobilization and skeletal muscles consume
-glucose is saved for the brain because it cannot used FAs
40 hours
-liver gluconeogenesis supplies 95% of glucose
- carbon comes from TAG and glucogenic amino acids
> 48 hours
-acetyl-coa accumulation from FA oxidation
-ketone body synthesis in liver, brain adapts
-rate of skeletal muscle breakdown decreases
-brain glucose demand drops
Metabolic changes in cancer cells
-increased glycolysis
-protein/nucleotide biosynthesis initiated form glycolytic intermedia buildup
-glutamine utilization from blood increases
-blood vessel growth due to increased lactate secretion
Type 1 Diabetes
-insulin dependent
-caused by pancreatic b-cell deficiency and failure to produce insulin
-autoimmune disease b/c the body attacks pancreatic b-cells
problems arise from hyperglycemia and uncontrolled metabolic responses
Type 2 diabetes
-not insulin dependent
-organs are insulin resistant
Type 1 diabetes treatment
insulin injections
Type 2 diabetes treatment
-Metformin- decreases glucose release by liver, increased AMPK activity
-TZD promotes insulin-stimulated glucose disposal in muscle, alters AMP/ATP ratio to indirectly stimulate AMPK
