Gluconeogenesis Flashcards
What are the two pathways that form “free” glucose
gluconeogenesis
glycogen degradation
convert glucose-6-P-phosphate to glucose.
Describe what occurs after carbohydrate consumption
insulin dependent glucose transport into adipose tissue, heart, and skeletal muscle.
insulin dependent glucose transport into liver and other tissues
glycolytic pathway activated
PDH is active in tissues that have mitochondria forms AcCoA
AcCoA metabolized by CAC
What occurs in the liver in the fed state
insulin cuases genes for glycolytic enzymes to be expressed. produce glucokinase, PFK1 and pyruvate kinase
Effects of glucagon and epi during the fasting state
block glycolysis. inhibit PFK2 which in hibits PFK1. inhibit pyruvate kinase.
decrease gene transcription glucokinase, PFK1, pyruvate kinase
Changes in the body from fed to fasting
during the fed state these are high: insulin, blood glucose, liver glycogen,
During fed state these are low: glucagon, free fatty acids, blood ketone bodies
during fasting these are high: glucagon, free fatty acids, blood ketone bodies
during fasting these are low: insulin, BGL, liver glycogen
What would occur of the glucose-6-phosphatase enzymes was not working properly?
gluconeogenesis and glycogen degradation could not occur. you cannot maintain normal blood glucose levels without eating for long periods of time.
How many ATPs does gluconeogenesis require
6 ATP
Synthesis of glucose from non-carb precursors
pyruvate, lactate, glycerol, glucogenic amino acids.
pyruvte is converted to oxaloacetate in a two step process
gluconeogenic precursors
lactate- general metabolism, RBC metabolism, muscle metabolism
glucogenic amino acids (alanine)- overnight degradation of muscle amino acids.
glycerol-degradation of adipose tissue and TAGs.
why are neonates at risk for hypoglycemia?
neonates brains are very dependent on glucose from glycogen degradationand gluconeogenesis. PEP carboxykinase is needed to make glucose from lactate or alanine, but it takes a few hours to induce its activity.
What 4 enzymes are required to reverse the three irrevesible steps of glycolysis
Mitochondial: Pyruvate carboxylase
Cytoplasmic- Phosphoenol pyruvate (PEP) carboxy kinase
Fructose 1,6 bisphosphate
Glucose 6 phosphate
Pyruvate carboxylase
mitochondrial enzyme that carboxylates pyruvate to form oxaloacetate. ATP provides the energy to add the carboxyl group to biotin, the carrier of the activated CO2 group. **acetyl CoA is an allosteric activator of this enzyme. **
Pyruvate carboxylase deficiency
Cannot convery pyruvate to oxaloacetate. causes accumulation of pyruvate in the plasma. the pyruvate gets converted to lactate by lactate dehydrogenase. This causes lactic acid build up. high alanine in the serum. cannot participate in gluconeogenesis or the ureas cycle.
causes failure to thrive, developmental delay, recurrent seizures, and metabolic acidosis
Glucose-6-phosphotase
essential enzyme required to releae glucose from the liver and into the circulaiton. required for gluconeogenesis ans glucogenolysis
Why can’t skeletal muscle synthesize glucose.
glucose-6-phosphatase is absent. make lactate instead.
Allosteric regulation of Glucokinase
Glucokinase: activated by insulin and glucose
Allosteric regulation of glucose-6-phosphatase
G-6-phosphotase: ihibited by insulin and glucose. Activated by glucagon.
Allosteric regulation of phosphofructo kinase
Phosphofructokinase: activated by F2,6BP and AMP. Inhibited by ATP and citrate
Allosteric regulation of Fructose1,6bisphosphatase
inhibted by F2,6BP and AMP
Allosteric regulation of pyruvate kinase
activated by: F1,6BP and glucose
inhibited by: glucagon and ATP
alloteric regulation of phosphoenolpyruvate carboxykinase (PEPCK)
activated by: glucagon
inhibited by: insulin
Allosteric regulation of pyruvate carboxylase
activated by acetyl CoA
Regulation for the synthesis of glycolytic enzymes
increased insulin and glucose. decreased cAMP (as a result of decreased glucagon or epi) a need for more ATP
glucokinase
PFK-1
pyruvate kinase
regulation for the synthesis of gluconeogenic enzymes
increased glucagon or epinephrine. starvation or fasted state. increased cAMP. resulting from less available energy (ATP)
glucose-6-phosphotase
Fructose-1,6-bisphosphotase
PEP carboxykinase
pyruvate carboxylase
How does ethanol metabolism cause hypoglycemia
ethanol dehydrogenase causes high NADH which opposes gluconeogenesis.
this removes pyruvate and oxaloacetate from the pool of gluconeogenic precursors by converting them to lactate and malate.
increased NADH leads to increased lactate formation. decreased NADH leads to decreased lactate formation.
Glucose-6-phosphotase deficiency
located in the ER. autosomal recessive disease.
interferes with gluconeogenesis and causes build up of glycogen in the liver
causes fasting intolerance, growth retardation, enlarged liver (accumulation of glycogen and fat), elevated serum uric acid and lactate.
