Lecture4-GLUCONEOGENESIS

Question 1

Where is the location of gluconeogenesis taken place in the cell?

Answer 1

Starts in the mitochondria, then cytosol then ends in the ER lumen of the liver

Question 2

what is the net product of gluconeogenesis?

Answer 2

-4ATP, -2 GTP, -2NADH
we are using energy to make glucose

Question 3

What are the precursors of glucogensis

Answer 3

lactate, amino acids, glycerol

NOT ACTYL COA

Question 4

Review: where is glycolysis located and net product?

Answer 4

Location: all cells, erythrocytes, brain and cns, muscle
net: +2ATP and +2 NADH

Question 5

What is the rate limiting step for gluconeogenic pathway?

Answer 5

fructose 1-6 bisphosphate

Question 6

What inhibits gluconeogenic pathway? with fructose 1-6 bisphosphatase

Answer 6

F2,6 BP

Question 7

What activates the gluconeogenic pathway? with fructose 1-6 bisphosphatase

Answer 7

glucagon

Question 8

What is the two spots you can inhibit the gluconeogenic pathway?

Answer 8

oxaloactate–> PEP with PEP carboxylokinase
F1,6BP –> F-6-P with F 1,6 Bisphosphatase

Question 9

What activates gluconeogenic pathway? with PEP carboxykinase

Answer 9

glucagon

Question 10

What inhibits gluconeogenic pathway? with PEP carboxykinase

Answer 10

insulin

Question 11

Where is ATP and GTP used for gluconeogenesis? and the enzymes (lower yield)

Answer 11

Pyruvate to OAA with pyruvate carboxylase ( ATP)
3PG to 1-3BGP with phosphoglyerate kinase (ATP)
OAA to PEP with PEP carboxykinase (GTP)

Question 12

Glucose 6-phosphate is located where?

Answer 12

on the luminal side of the ER in Liver

Question 13

What happens in T1D?

Answer 13

lack of insulin

Question 14

What happens in T2D? and with the gluconeogenic pathway

Answer 14

-insulin resistance
-cause the gluconeogeneis pathway to be uninhibited when when blood glucose concentration is high

Question 15

What is the drug to treat T2D?

Answer 15

Metformin

Question 16

How does metformin work?

Answer 16

stimulated liver AMP activated protein kinase which causes the inhibition of glucogenesis

Question 17

what upregulates PEPCK?

Answer 17

glucagon

Question 18

What inhibit PEPCK?

Answer 18

insulin

Question 19

What is phosphorylated to start transcription of PEPCK?

Answer 19

CREB

Question 20

What is a direct stimulator to start transcription of PEPCK?

Answer 20

glucocorticoid

Question 21

F/T: breakdown of glycogen causes your blood sugar to rise

Answer 21

True

Question 22

The muscle does not contain this enzyme that is found in the liver?

Answer 22

glucose 6-phosphatase

Question 23

what does the the liver do with Glucose 6 phosphatase

Answer 23

releases glucose to the blood to be taken up by brain and active muscle

Question 24

what does muscle do with glucose 6-phosphatase?

Answer 24

does not have It so it retains g-6-p to be used for energy (glycolysis)

Question 25

what is the cori cycle?

Answer 25

Lactate recycled from erythrocytes (or muscle cells) to liver

Question 26

what is the alanine cycle?

Answer 26

alanine recycled from muscle cells to liver

Question 27

What is the function of glycogen in the liver?

Answer 27

synthesis and breakdown of glycogen is regulated to maintain blood glucose levels

Question 28

What is the function of glycogen in the muscles?

Answer 28

the synthesis and breakdown of glycogen is regulated to meet the energy requirements of the muscle cell

Question 29

what is the RLE for glycogen metabolism?

Answer 29

glycogen synthase and glycogen phosphorylase

Question 30

where is glycogen stored?

Answer 30

liver, muscle and adipose tissue

Question 31

what is glycogenin?

Answer 31

OH linkage for additional linkages (1,4) and tyrosine residue as a primer

Question 32

What is the energy source for glycogen synthesis?

Answer 32

UDP-glucose

Question 33

is glycogenin and UDP self-glucosylating?

Answer 33

yes

Question 34

what adds the 1,4 linkages for glycogen synthesis?

Answer 34

glycogen synthase

Question 35

what adds the 1,6 linkages and what looks does it give?

Answer 35

branching enzyme and 3-D

Question 36

What is glycogenic-glycogen complex

Answer 36

final product with 1,4 and 1,6 linkages

Question 37

What linkage is hydrophobic and why?

Answer 37

1,4 linkages and because it lost two water molecules

Question 38

What does a cross-sectional of glycogen look like?

Answer 38

core protein of glycogenin is surround by branches of glucose units

Question 39

What contributes to blood glucose? and does not contribute

Answer 39

degradation of glycogen in liver contributes to blood glucose but not degradation of glycogen in muscles

Question 40

Why can the liver contribute to Blood glucose and muscles cannot?

Answer 40

liver has glucose 6 phosphatase to breakdown and muscle does not

Question 41

what happens when we degradate glycogen in our body

Answer 41

increase blood sugar levels

Question 42

what cleaves 1,4 linkages?

Answer 42

phosphorylase

Question 43

Transferase does what in degradation?

Answer 43

move everything except sugar connected to 1,6 linkage

Question 44

what cleaves 1,6 linkages ?

Answer 44

a-1,6 glucosidase

Question 45

what happens when blood glucose levels are high?

Answer 45

insulin stimulates glycogen synthesis

Question 46

what regulated blood glucose levels?

Answer 46

glycogen metabolism in liver

Question 47

what molecule are muscle cells responsive to for glycogen breakdown? what happens?

Answer 47

epinephrine increase cAMP to get G-1-P--> G-6-P to get pyruvate for glycolysis since we do not have the enzyme

Question 48

what are liver cells responsive to for glycogen breakdown? what happens?

Answer 48

glycogen and somewhat epinephrine increases cAMP--> G-1-P---> G-6-P to glucose

Question 49

what are glycogen storage diseases?

Answer 49

inborn errors of glycogen metabolism; deficiencies of enzymes necessary for glycogen synthesis or breakdown

Question 50

Von Gierke's disease

Answer 50

glucose -6-phosphase deficiency - final step in glyconegesis and glycogenolysis to produce glucose is defected - growth failure, lactic acidosis, no pathologic muscle symptoms

Question 51

Cori's disease

Answer 51

glycogen debranching enzyme deficiency - defect in glycogenolysis -myopathies

Question 52

Anderson disease

Answer 52

glycogen branching enzyme deficiency - defect in glycogen synthesis -failure to thrive -death at about age 5 years -no pathologic muscle symptoms

Question 53

McArdle disease

Answer 53

Glycogen phosphorylase deficiency - defect in glycogenolysis - exercise induced muscle cramps -rhabdomyolysis (breakdown of damage skeletal muscle tissue)