Theme 3: Metabolism: Storage, Retrieval, and Synthesis of Fats and Carbohydrates Flashcards
Normal blood glucose is?
under 100
when treating high blood glucose for T2DM, it is also important to address…
high cholesterol levels
What is the brains primary and secondary source of energy?
First, glucose. Then, ketones.
How/where are ketones produced?
Free fatty acid oxidation at the liver
Anabolism- Fed state: what hormone is high and what are the processes that are associated with it?
Is associated with insulin secretion; active processes of glycogenesis, protein synthesis and TG synthesis.
Anabolism- Fed state: what hormone is high and what are the processes that are associated with it?
Is associated with insulin secretion; active processes of glycogenesis, protein synthesis and TG synthesis.
What type of transporter and where does insulin act.
insulin receptors are on muscle and adipose tissue and trigger glut 4 receptors to the cell surface. This can be also triggered with exercise.
Drug: insulin
it is injected. tends to cause weight gain
Drug: sulfonylurea
ie. glucotrol, glipizide- triggers insulin secretion
Drug: glucatrol
sulfonylurea- insulin secretion by beta cells
Drug: glipizide
sulfonylurea- triggers insulin secretion by beta cells.
Drug: metformin
biguinide. inhibits gluconeogenesis by the liver and enhances glut 4 translocation
drug: pioglitazone
thiazolidines: enhances insulin receptor sensitivity and glut 4 translocation in fat cells. bu tis associated with an increased risk of MI and stroke, so it is not really used anymore.
exentide
incretin mimetic: naturally occuring homrone in response to food intake: increases the glucose dependent insulin response by the pancrease and is postitively associated with weight loss
sitagliptin
dipeptyl peptidase 4 inhbitor. aslo increases incretin availablity be decreasing degradation
number one risk factor for diabetes is
obesity
it is important to use what drugs in addition to insulin promoting drugs?
statins and aspirin, to lower lipids and decrease inflammation- to prevent cardio disease.
standard drugs for diabetics
statin with metformin/insulin
what is statin
lipid lowering drug, by partial inhibition of hmg-coa reducatase
checking lactate levels diabetes
to check for anaerobic metabolism
aerobic metabolism
pyruvate to TCA & ETC, to produce CO2 and H20
Insulin Independent glucose transporters: Glycolysis enzyme and location:
Glucokinase, at liver, pancreatic B cell, and Brain
Insulin DEPENDENT glucose transporters
at the muscle, hexokinase.
insulin and glucagon
maintain blood glucose levels. glucagon, when blood glucose is low, increases glucose release from the liver to the blood. insulin when glucos is high after a meal, decreases glucose release from the liver and actually increases glygogenesis.
Glucokinase/ Hexokinase
converts glucose to g6p in glycolysis
g6p phophatase
converts g6p to glucose in gluconeogenesis; this enzyme is key for hepatic glucose release
PEP carboxylase
TCA intermediates for gluconeogenesis
Glycogen synthase
glycogenesis
Glycogen phosphatase
Glycogenolysis
Energy: Muscle, what does it use?
It uses glucose or fatty acids, and can store glucose as glygogen
GLUT 2 Where?
Liver and pancreas, glucose uptake is proportional to the plasma glucose concentration. (insulin independent)
GLUT 3 Where?
Brain, glucose uptake in the brain is at a steady state over the physiological range of glucose concentration, so it is glucose and insulin independent. it has the highest affinity for glucose because it has the lowest km.
GLUT 4 Where
Glut 4 is at the muscle and fat. it is translocation to the cell surface is dependent on insulin or exercise.
Hexokinase
Is the type glycolysis enzyme in most cells. it is saturated at a low glucose concentration..
Glucokinase:
is in the liver, and pancreatic beta cells, it as as the glucose sensor and has a very high km. because the liver is the ‘altruistic organ’ this allows it to have access to glucose after all the other organs are accounted for.
GKRP: glucokinase regulatory protein
binds glucokinase in the nucleus when glucose levels are low. it is released into the cytoplasm to be active then glucose levels are higher. There is negative feedback as g6p is converted to f6p, which returns GK to the nucleus.
Glycolysis regulation
is by allosteric and hormonal regulation (insulin and allosteric regulation of GK, HK)
phosphofructokinase, PFK: function and regulation:
Glycolysis: f6p to f1,6,bp. (+) by F2BP, AMP (-) ATP Citrate, H+
Irreversible/ Regulated steps of Glycolysis
PFK and Pyruvate Kinase, allosterically regulated
PFK -2: Function
PFK 2 phosporylated f6p to f26bp, which is in turn a postive allosteric regulator for the next glycolysis enzyme, PFK. it is a BIFUNCTIONAL ENZYME with kinase and phosphatase activity
Glucagon on PFK2
Glucagon phosphorylates PFK2, which activates its phosphatase activity of F26BP to F6P, less F26BP means that less glycolysis is taking place (hormonal reg of glycolysis)– THIS IS IN LIVER! OPPOSITE EFFECT TO INCREASE GLYCOLYSIS IN HEART MUSCLE WHEN PHOSPHORYLATED BY ACTION OF EPI AND PKA
Insulin on PFK2
Insulin, by a complicated pathway, increases F26BP, via PFK2 kinase activity, and increases glycolysis (hormonal reg of glycolysis)
Epinephrine effect on PFK2 and glycolysis in the heart muscle
the PFK2 has a different isoform in heart muscle where Epi will phosphorylate it. This wil actually increase f26bp and promote glycolysis
PFK2 effect in skeletal muscle
there is none, PFK 2 is not applicable in skeletal muscle.
Pyruvate kinase regulation by glucagon
Glucagon phosphorylates PK to decrease its activity
Respiration in normal vs. cancer cells.
In cancer cells, they only use anaerobic respiration, generating lactate, even in aerobic conditions.
T/F: PDH is inactive when phosphorylated by kinase
True. Also, Ca is a strong activator of the phosphatase that dephos PDH and makes it active.
3 Regulated steps of TCA:
PDH, Isocitrate dehydrogenase, a-ketoglutarate dehydrogenase
Unique Enzymes for Gluconeogenesis:
6ATP per 1 glucose synthesis. Pyruvate carboxylase (Pyruvate to OAA), PEPCK (phosphoenol pyruvate carbozy kinase, OAA to PEP), F16BP, and Glucose 6 phosphatase (g6p to g)
PEPCK regulated for what process and how
PEPCK transcription is regulated for gluconeogenesis, it is decreased by insulin and increased by fasting, glucocorticoids, glycogen, and thyroid homrone. (PEPCK transgenic mice can run much better)
there is reciprocal regulation of gluconeogenesis and glycolysis. What is the corresponding enzyme to F16Bisphosphatase in glycolysis?
PFK
T/F, G6p cannot be exported out of the cell, it needs to be converted to G by G6P-Phosphatase first
this is true. this is what allows the liver to release G to other organs.
5 enzymes required to export glucose from the liver
g6p transporter, CA binding stabilizing protein, G6Pase, Glucose tranporter, Pi transporter.
Prime function of gluconeogenesis
the liver provide constant glucose to the brain.
Epi, glucagon & insulin, phos/dephos
Epi & Glucagon=phosphorylates, activating gluconeogenesis, glycogenolysis enzymes Insulin dephosphorylates, activating kinases/ activates glycolysis and glycogenolysis enzymes.
substrates for gluconeogeneisis
lacatate, alanine, glycerol from muscle, RBC, renal medulla, and fat –> to the liver for gluconeogenesis, and then to the brain as glucose
reciprocal regulation of glycogenesis/glycogenoslysis
glycogen synthase is active when dephosphorylated. this is stimulated by insulin. glycogen phosphorylase, breakdown enzymes are active when phosphorylated by epi or glucagon. This will in turn increase glycogen breakdown to form glucose
glycogen synthase/phosphorylase are receiprocally regulated
Glucose 6-phoshate activates glycogen synthase, inhibits glycogen phosphorylase ATP inhibits phosphorylase Glucose inhibits phosphorylase (in liver) Ca++ and AMP activate phosphorylase (in muscle)
Function of Actyel Coa Carboxylase (ACC)
for fatty acid synthesis: regulated by dephos and phos. active when dephos. opposite of hormone sensitive lipase
Hormone sensitive lipase
first enzyme of lipolysis for gluconeogenesis. reciprocally reg with ACC
Why do patients with liver failure get hypoglycemia
.
Can fatty acids be converted to glucose?
.
How and why is blood glucose maintained in a prolonged fast?
.
Endocrine cells in the pancreas
islets of langerhaans
