Theme 3: Metabolism: Storage, Retrieval, and Synthesis of Fats and Carbohydrates

Question 1

Normal blood glucose is?

Answer 1

under 100

Question 2

when treating high blood glucose for T2DM, it is also important to address…

Answer 2

high cholesterol levels

Question 3

What is the brains primary and secondary source of energy?

Answer 3

First, glucose. Then, ketones.

Question 4

How/where are ketones produced?

Answer 4

Free fatty acid oxidation at the liver

Question 5

Anabolism- Fed state: what hormone is high and what are the processes that are associated with it?

Answer 5

Is associated with insulin secretion; active processes of glycogenesis, protein synthesis and TG synthesis.

Question 6

Anabolism- Fed state: what hormone is high and what are the processes that are associated with it?

Answer 6

Is associated with insulin secretion; active processes of glycogenesis, protein synthesis and TG synthesis.

Question 7

What type of transporter and where does insulin act.

Answer 7

insulin receptors are on muscle and adipose tissue and trigger glut 4 receptors to the cell surface. This can be also triggered with exercise.

Question 8

Drug: insulin

Answer 8

it is injected. tends to cause weight gain

Question 9

Drug: sulfonylurea

Answer 9

ie. glucotrol, glipizide- triggers insulin secretion

Question 10

Drug: glucatrol

Answer 10

sulfonylurea- insulin secretion by beta cells

Question 11

Drug: glipizide

Answer 11

sulfonylurea- triggers insulin secretion by beta cells.

Question 12

Drug: metformin

Answer 12

biguinide. inhibits gluconeogenesis by the liver and enhances glut 4 translocation

Question 13

drug: pioglitazone

Answer 13

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.

Question 14

exentide

Answer 14

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

Question 15

sitagliptin

Answer 15

dipeptyl peptidase 4 inhbitor. aslo increases incretin availablity be decreasing degradation

Question 16

number one risk factor for diabetes is

Answer 16

obesity

Question 17

it is important to use what drugs in addition to insulin promoting drugs?

Answer 17

statins and aspirin, to lower lipids and decrease inflammation- to prevent cardio disease.

Question 18

standard drugs for diabetics

Answer 18

statin with metformin/insulin

Question 19

what is statin

Answer 19

lipid lowering drug, by partial inhibition of hmg-coa reducatase

Question 20

checking lactate levels diabetes

Answer 20

to check for anaerobic metabolism

Question 21

aerobic metabolism

Answer 21

pyruvate to TCA & ETC, to produce CO2 and H20

Question 22

Insulin Independent glucose transporters: Glycolysis enzyme and location:

Answer 22

Glucokinase, at liver, pancreatic B cell, and Brain

Question 23

Insulin DEPENDENT glucose transporters

Answer 23

at the muscle, hexokinase.

Question 24

insulin and glucagon

Answer 24

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.

Question 25

Glucokinase/ Hexokinase

Answer 25

converts glucose to g6p in glycolysis

Question 26

g6p phophatase

Answer 26

converts g6p to glucose in gluconeogenesis; this enzyme is key for hepatic glucose release

Question 27

PEP carboxylase

Answer 27

TCA intermediates for gluconeogenesis

Question 28

Glycogen synthase

Answer 28

glycogenesis

Question 29

Glycogen phosphatase

Answer 29

Glycogenolysis

Question 30

Energy: Muscle, what does it use?

Answer 30

It uses glucose or fatty acids, and can store glucose as glygogen

Question 31

GLUT 2 Where?

Answer 31

Liver and pancreas, glucose uptake is proportional to the plasma glucose concentration. (insulin independent)

Question 32

GLUT 3 Where?

Answer 32

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.

Question 33

GLUT 4 Where

Answer 33

Glut 4 is at the muscle and fat. it is translocation to the cell surface is dependent on insulin or exercise.

Question 34

Hexokinase

Answer 34

Is the type glycolysis enzyme in most cells. it is saturated at a low glucose concentration..

Question 35

Glucokinase:

Answer 35

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.

Question 36

GKRP: glucokinase regulatory protein

Answer 36

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.

Question 37

Glycolysis regulation

Answer 37

is by allosteric and hormonal regulation (insulin and allosteric regulation of GK, HK)

Question 38

phosphofructokinase, PFK: function and regulation:

Answer 38

Glycolysis: f6p to f1,6,bp. (+) by F2BP, AMP (-) ATP Citrate, H+

Question 39

Irreversible/ Regulated steps of Glycolysis

Answer 39

PFK and Pyruvate Kinase, allosterically regulated

Question 40

PFK -2: Function

Answer 40

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

Question 41

Glucagon on PFK2

Answer 41

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

Question 42

Insulin on PFK2

Answer 42

Insulin, by a complicated pathway, increases F26BP, via PFK2 kinase activity, and increases glycolysis (hormonal reg of glycolysis)

Question 43

Epinephrine effect on PFK2 and glycolysis in the heart muscle

Answer 43

the PFK2 has a different isoform in heart muscle where Epi will phosphorylate it. This wil actually increase f26bp and promote glycolysis

Question 44

PFK2 effect in skeletal muscle

Answer 44

there is none, PFK 2 is not applicable in skeletal muscle.

Question 45

Pyruvate kinase regulation by glucagon

Answer 45

Glucagon phosphorylates PK to decrease its activity

Question 46

Respiration in normal vs. cancer cells.

Answer 46

In cancer cells, they only use anaerobic respiration, generating lactate, even in aerobic conditions.

Question 47

T/F: PDH is inactive when phosphorylated by kinase

Answer 47

True. Also, Ca is a strong activator of the phosphatase that dephos PDH and makes it active.

Question 48

3 Regulated steps of TCA:

Answer 48

PDH, Isocitrate dehydrogenase, a-ketoglutarate dehydrogenase

Question 49

Unique Enzymes for Gluconeogenesis:

Answer 49

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)

Question 50

PEPCK regulated for what process and how

Answer 50

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)

Question 51

there is reciprocal regulation of gluconeogenesis and glycolysis. What is the corresponding enzyme to F16Bisphosphatase in glycolysis?

Answer 51

PFK

Question 52

T/F, G6p cannot be exported out of the cell, it needs to be converted to G by G6P-Phosphatase first

Answer 52

this is true. this is what allows the liver to release G to other organs.

Question 53

5 enzymes required to export glucose from the liver

Answer 53

g6p transporter, CA binding stabilizing protein, G6Pase, Glucose tranporter, Pi transporter.

Question 54

Prime function of gluconeogenesis

Answer 54

the liver provide constant glucose to the brain.

Question 55

Epi, glucagon & insulin, phos/dephos

Answer 55

Epi & Glucagon=phosphorylates, activating gluconeogenesis, glycogenolysis enzymes Insulin dephosphorylates, activating kinases/ activates glycolysis and glycogenolysis enzymes.

Question 56

substrates for gluconeogeneisis

Answer 56

lacatate, alanine, glycerol from muscle, RBC, renal medulla, and fat --\> to the liver for gluconeogenesis, and then to the brain as glucose

Question 57

reciprocal regulation of glycogenesis/glycogenoslysis

Answer 57

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

Question 58

glycogen synthase/phosphorylase are receiprocally regulated

Answer 58

Glucose 6-phoshate activates glycogen synthase, inhibits glycogen phosphorylase ATP inhibits phosphorylase Glucose inhibits phosphorylase (in liver) Ca++ and AMP activate phosphorylase (in muscle)

Question 59

Function of Actyel Coa Carboxylase (ACC)

Answer 59

for fatty acid synthesis: regulated by dephos and phos. active when dephos. opposite of hormone sensitive lipase

Question 60

Hormone sensitive lipase

Answer 60

first enzyme of lipolysis for gluconeogenesis. reciprocally reg with ACC

Question 61

Why do patients with liver failure get hypoglycemia

Answer 61

.

Question 62

Can fatty acids be converted to glucose?

Answer 62

.

Question 63

How and why is blood glucose maintained in a prolonged fast?

Answer 63

.

Question 64

Endocrine cells in the pancreas

Answer 64

islets of langerhaans