Carbohydrate Metabolism (3 lectures) (Note: + means induces, - means represses) Flashcards
Standard values for 75 gram oral glucose:
1) Fasting
2) 1 Hour
3) 2 hour
1) 60-100 mg/dL
2) less than 200 mg/dL
3) less than 140 mg/dL
Glycemic index
Indicator of how rapidly glucose levels rise (after eating food)
1) GI of fruit, veggies, milk
2) GI of corn flakes, baked potatoes
1) less than 50
2) greater than 70
Hormones regulating metabolism
Insulin, Glucagon, Epinephrine, and Cortisol
How does insulin regulate metabolism?
Promotes fuel storage after meal, promotes growth
It binds to receptors on muscle, adipose tissue, and stimulates GLUT4 receptors
Where is insulin produced?
It is produced as a pre-pro-hormone in the beta cell of the islets of Langerhans (pancreas) and is stored in vesicles for release. It responds directly to increased intracellular glucose through the GLUT2 receptor
What is the mechanism of the response (of insulin from the GLUT2 receptor)?
Increasing [ATP] in the cell inhibits an ATP dependent potassium channel that depolarizes the cell and allows extracellular calcium to enter
The insulin receptor, ____, is membrane bound and is a ____.
GLUT4,
tyrosine kinase receptor
How does glucagon regulate metabolism?
It mobilizes fuel, maintains blood glucose during fasting
It acts through a glucagon receptor that activates a G-protein, an ATP cyclase, and a cAMP dependent kinase
Where is glucagon produced?
The peptide hormone is produced in a pre-pro form in the alpha cells of the pancreas. It’s release is directly suppressed by glucose and insulin
How does epinephrine regulate metabolism?
It mobilizes fuel during acute stress.
It activates glycogen phosphorylase to release glucose but does not stimulate gluconeogenesis.
In muscle it activates a G protein and an adenylate cyclase to activate protein kinase A (similar to glucagon). In liver it binds alpha-agonist receptor signals through IP3 and calcium to activate multiple kinases
How does cortisol regulate metabolism?
It alters long term metabolism. It binds an intracellular receptor and moves to the nucleus where it controls the gene trascription. It stimulates gluconeogenesis and fatty acid release from adipose tissue (influences long-term fuel mobilization).
Epinephrine is also known as ___.
adrenaline
Cortisol is also known as ___.
Glucocorticoid
The major anabolic hormone in the body
insulin
Insulin stimulates
Protein synthesis, glycogen synthesis, and triglyceride synthesis
Preproinsulin has an ____ that is cleaved when perproinsulin becomes proinsulin.
N-terminal signal peptide
Proinsulin is cleaved in ___ location(s) to form mature insulin (A and B chains). The internal peptide cleaved from insulin is called the ____ and can be measured to distinguish endogenous insulin from injected insulin.
two,
C-peptide
What releases vesicles of insulin?
calcium
____ closes potassium channels and stimulates ___ influx, which is useful with patients that have functional beta cells (type _ diabetes)
Sulfonylureas (glipizide, glyburide),
calcium,
II (two)
Insulin peaks about __ minutes after high carbohydrate meals
45
What does salivary amylase do?
It digests starch to maltose (disaccharide of glucose), trisaccharides, and dextrins (4-9 glucosyl units)
What does stomach acid to?
It inactivates amylase (I’m not positive why but that’s what the slide says)
What occurs in the duodenum?
Neutralization of acid, alpha-amylase from pancreas forms more maltose, ditrisaccharides, dextrins
What enzymes are present in the small intestine brush border complexes?
glucoamylase (cleaves alpha 1-4 glycosidic bonds), sucrase-isomaltase, trehalase (cleaves threhalose found in mushrooms) and lactase (cleaves lactose into glucose, galactose)
What does glucoamylase do?
Cleaves alpha 1-4 glycosidic bonds
What does lactase do?
Cleaves lactose into glucose and galactose
Where are GLUT1 receptors?
RBCs, brain endothelial cells (High affinity for glucose)
Where are GLUT2 receptors?
pancreas, liver (low affinity for glucose)
Where are GLUT3 receptors?
neurons
Where are GLUT4 receptors?
fat, muscle, heart (insulin induced)
Where are GLUT5 receptors?
testis (actually a fructose transporter)
How is glucose absorbed into cells?
Through a GLUT family of transporters
What happens in lactose intolerance?
lactase on the intestinal brush border begins to decrease (which is natural) and lactose is not absorbed and is instead metabolized by colonic bacteria. This causes gas and diarrhea (methane is made, the osmotic effect creates diarrhea)
Some sugars that are undigested
raffinose, soluble fiber (pectin, gums)
What are the fates of glucose-6-phosphate?
lactate, ribose and NADPH, glucose (serum glucose levels), or Co2 and water (TCA cycle). Also glycogen.
a) Function of glycogen
1) in muscle
2) in liver
a) Glucose reserve
1) provides glucose for glycolysis during anaerobic exercise
2) Glycogen is degraded and the glucose released into the blood stream to support serum levels during fasting
What is glycogen?
Branched chain of glucose molecules connected by alpha-1,4 linkages and alpha-1,6 branches
What protein is associated with glycogen synthesis?
Glycogen synthesis initiates on the protein glycogenin (autoglycosylation with UDP-glucose on Tyr)
UDP-glucose is added to the ____ end of the glycogen molecule by ___.
non-reducing,
glycogen synthase
Chains over ___ residues are ____ and attached via ____ to create a branch site. (Glycogen)
11,
hydrolyzed,
alpha-1,6
What vitamin is required to convert glycogen to glucose?
Vitamin B6 (pyridoxine)
Phosphorylase stalls within __ glucose units of a branch. (releasing glycogen)
four
Glycogen degradation II debranching enzyme has both ___ and ___ activity and transfers ___ glucose units.
transferase,
hydrolase,
3
What is McArdle’s disease?
It is a lack of muscle glycogen phosphorylase. It causes rhabdomyolysis and myoglobinuria.
What regulates glycogen phosphorylase?
Phosphorylase-kinase activates/phosphorylates it (glycogen phosphorylase-b). cAMP increases activity and phosphoprotein phosphatase (which is activated by insulin) inactivates or dephosphorylates glycogen phosphorylase-a.
Phosphorylase-kinase ____ phophorylase-b.
Phosphorylates/activates
Phosphorylated glycogen phosphorylase is ____.
The activated form of glycogen phosphorylase