Lecture4-GLUCONEOGENESIS Flashcards
Where is the location of gluconeogenesis taken place in the cell?
Starts in the mitochondria, then cytosol then ends in the ER lumen of the liver
what is the net product of gluconeogenesis?
-4ATP, -2 GTP, -2NADH
we are using energy to make glucose
What are the precursors of glucogensis
lactate, amino acids, glycerol
NOT ACTYL COA
Review: where is glycolysis located and net product?
Location: all cells, erythrocytes, brain and cns, muscle
net: +2ATP and +2 NADH
What is the rate limiting step for gluconeogenic pathway?
fructose 1-6 bisphosphate
What inhibits gluconeogenic pathway? with fructose 1-6 bisphosphatase
F2,6 BP
What activates the gluconeogenic pathway? with fructose 1-6 bisphosphatase
glucagon
What is the two spots you can inhibit the gluconeogenic pathway?
oxaloactate–> PEP with PEP carboxylokinase
F1,6BP –> F-6-P with F 1,6 Bisphosphatase
What activates gluconeogenic pathway? with PEP carboxykinase
glucagon
What inhibits gluconeogenic pathway? with PEP carboxykinase
insulin
Where is ATP and GTP used for gluconeogenesis? and the enzymes (lower yield)
Pyruvate to OAA with pyruvate carboxylase ( ATP)
3PG to 1-3BGP with phosphoglyerate kinase (ATP)
OAA to PEP with PEP carboxykinase (GTP)
Glucose 6-phosphate is located where?
on the luminal side of the ER in Liver
What happens in T1D?
lack of insulin
What happens in T2D? and with the gluconeogenic pathway
-insulin resistance
-cause the gluconeogeneis pathway to be uninhibited when when blood glucose concentration is high
What is the drug to treat T2D?
Metformin
How does metformin work?
stimulated liver AMP activated protein kinase which causes the inhibition of glucogenesis
what upregulates PEPCK?
glucagon
What inhibit PEPCK?
insulin
What is phosphorylated to start transcription of PEPCK?
CREB
What is a direct stimulator to start transcription of PEPCK?
glucocorticoid
F/T: breakdown of glycogen causes your blood sugar to rise
True
The muscle does not contain this enzyme that is found in the liver?
glucose 6-phosphatase
what does the the liver do with Glucose 6 phosphatase
releases glucose to the blood to be taken up by brain and active muscle
what does muscle do with glucose 6-phosphatase?
does not have It so it retains g-6-p to be used for energy (glycolysis)
what is the cori cycle?
Lactate recycled from erythrocytes (or muscle cells) to liver
what is the alanine cycle?
alanine recycled from muscle cells to liver
What is the function of glycogen in the liver?
synthesis and breakdown of glycogen is regulated to maintain blood glucose levels
What is the function of glycogen in the muscles?
the synthesis and breakdown of glycogen is regulated to meet the energy requirements of the muscle cell
what is the RLE for glycogen metabolism?
glycogen synthase and glycogen phosphorylase
where is glycogen stored?
liver, muscle and adipose tissue
what is glycogenin?
OH linkage for additional linkages (1,4) and tyrosine residue as a primer
What is the energy source for glycogen synthesis?
UDP-glucose
is glycogenin and UDP self-glucosylating?
yes
what adds the 1,4 linkages for glycogen synthesis?
glycogen synthase
what adds the 1,6 linkages and what looks does it give?
branching enzyme and 3-D
What is glycogenic-glycogen complex
final product with 1,4 and 1,6 linkages
What linkage is hydrophobic and why?
1,4 linkages and because it lost two water molecules
What does a cross-sectional of glycogen look like?
core protein of glycogenin is surround by branches of glucose units
What contributes to blood glucose? and does not contribute
degradation of glycogen in liver contributes to blood glucose but not degradation of glycogen in muscles
Why can the liver contribute to Blood glucose and muscles cannot?
liver has glucose 6 phosphatase to breakdown and muscle does not
what happens when we degradate glycogen in our body
increase blood sugar levels
what cleaves 1,4 linkages?
phosphorylase
Transferase does what in degradation?
move everything except sugar connected to 1,6 linkage
what cleaves 1,6 linkages ?
a-1,6 glucosidase
what happens when blood glucose levels are high?
insulin stimulates glycogen synthesis
what regulated blood glucose levels?
glycogen metabolism in liver
what molecule are muscle cells responsive to for glycogen breakdown? what happens?
epinephrine
increase cAMP to get G-1-P–> G-6-P to get pyruvate for glycolysis since we do not have the enzyme
what are liver cells responsive to for glycogen breakdown? what happens?
glycogen and somewhat epinephrine
increases cAMP–> G-1-P—> G-6-P to glucose
what are glycogen storage diseases?
inborn errors of glycogen metabolism; deficiencies of enzymes necessary for glycogen synthesis or breakdown
Von Gierke’s disease
glucose -6-phosphase deficiency
- final step in glyconegesis and glycogenolysis to produce glucose is defected
- growth failure, lactic acidosis, no pathologic muscle symptoms
Cori’s disease
glycogen debranching enzyme deficiency
- defect in glycogenolysis
-myopathies
Anderson disease
glycogen branching enzyme deficiency
- defect in glycogen synthesis
-failure to thrive
-death at about age 5 years
-no pathologic muscle symptoms
McArdle disease
Glycogen phosphorylase deficiency
- defect in glycogenolysis
- exercise induced muscle cramps
-rhabdomyolysis (breakdown of damage skeletal muscle tissue)
