Carbohydrate Metabolism Flashcards
What is the only type of fuel that RBCs use and brain uses when not starving
Glucose, via glycolysis
GLUT1 and GLUT2 transporter location/affinity
GLUT1- ubiquitous, but high expression in RBC/brain
High affinity
GLUT2- Liver, low affinity
GLUT3 and GLUT4 transporter location/affinity
GLUT3- neurons, high affinity
GLUT4- skeletal muscle, heart, adipose tissue- insulin dependent- stored in vesicles and transported to membrane when triggered by insulin
Glyceraldehyde-3-phosphate–> 1,3-BPG reaction is carried out by what enzyme and creates what side product
Carried out by G3P dehydrogenase and creates 2 NADH
1,3-BPG–>3PG is carried out by what enzyme and has what side product
Phosphoglycerate kinase and makes 2 ATP
PEP–>Pyruvate carried out by what enzyme and has what side product
Pyruvate kinase and makes 2 ATP
Which two reactions in the early phase of glycolysis require ATP
Glucose–>G6P
F6P–>F1,6-BP
Glucokinase vs hexokinase
Glucokinase is only located in liver/pancreas, has lower affinity, and is not affected by G6P concentration as much. Insulin induces its synthesis, glucagon inhibits
What is Tarui disease
Deficiency in PFK-1
Exercise induced muscle cramps/weakness
Most defects in glycolytic enzymes cause what, and why
Hemolytic anemia, because RBCs do not have mitochondria so they are affected the most
Type I diabetes
Insulin deficiency due to loss of pancreatic b cells
Type II diabetes
Insulin resistance that progresses to loss of b cell function
Clinical markers of hemolytic anemia
Elevated lactate dehydrogenase, unconjugated bilirubin
Fanconi-Bickel syndrome
Mutation in GLUT2 transporter in liver/pancreas, unable to take up glucose
-Fasting hypoglycemia
Activation/inhibition of pyruvate kinase is done by who, and is PK activated/inhibited by phosphorylation
Activation- F1,6BP, Insulin
Inhibition- ATP, Alanine, Glucagon
Inhibited by phosphorylation, which means insulin stimulates protein phosphatases
Gluconeogenesis occurs where
Liver, kidney, small intestine
First reaction in gluconeogenesis, reactants, products, enzyme
Pyruvate + ATP CO2–> OAA
Pyruvate carboxylase
What are activators and inhibitors of Fructose 1,6 biphosphatase
Activators- Cortisol and citrate
Inhibitors- AMP and F26BP
How is G6P transported where it needs to be for conversion to glucose, and where does it need to be?
Conversion occurs in ER
G6P transported into ER, Glucose and Phosphate transported out
What does the cori cycle do
Links lactate produced by glycolysis to gluconeogenesis in liver
-Prevents lactate accumulation, regenerates glucose
F1,6BP deficiency
Hypoglycemia, lactic acidosis, ketosis
Von gerke disease
Deficiency in glucose 6-phosphate
Dietary source of Fructose is
Sucrose- cleaved by sucrase to give fructose and glucose
Dietary source of Galactose is
Lactose- cleaved by lactase to give galactose and glucose
Fructose uptake is mediated by what transporter
GLUT5
Galactose uptake is mediated by what transporter
SGLT1
Why is metabolism of fructose faster than glucose
Because it bypasses PFK1, the rate limiting step of glycolysis
Which cells lack sorbitol dehydrogenase, and was is the result
Kidneys, retina, schwann cells. Sorbitol cannot be converted to fructose and accumulates, causing water to enter cell. Retinopathy, cataracts, peripheral neuropathy
What is the result of high fructose diet
Fructose derived G3P and DHAP are processed to pyruvate and acetyl CoA in unregulated fashion. Excess Acetyl CoA is converted to fatty acids which accumulate in liver and cause fatty liver
Galactosemia cause and effects
Deficiency in galactose-1-P uridyl transferase
-Cataracts, enlarged liver, mental retardation
Oxidative phase of PPP is best for which cellular need
Nucleotide synthesis in rapidly dividing cells
Non oxidative phase of PPP is best for which cellular need
NADPH production- non oxidative products are channeled into gluconeogenesis for re-entry into PPP
What is the rate limiting enzyme in PPP, what happens if it is deficient
G6P Dehydrogenase- if deficient, hemolytic anemia presents when NADPH need is elevated
Glycogen is stored where
In liver, muscles mainly
What is the rate limiting enzyme in glycogenesis, and what does it do
Glycogen synthase- catalyzes transfer of glucose from UDP-glucose to non reducing end of glycogen
What is the name of the branching enzyme in glycogenesis
Glucosyl (4:6) transferase
What is the rate limiting step in glycogenolysis
Cleavage of glucose residue as glucose-1-phosphate by glycogen phosphorylase
What is the name of the debranching enzyme
Transferase (4:4) transfers last 3/4 glucose residues to end of main glycogen chain, then a-1,6-glucosidase cleaves 1 remaining glucose
Differential outcome of Glucose-1-phosphate in liver and muscle
Liver can directly convert G1P into glucose. Muscle cells lack the necessary enzymes and must use it for energy via glycolysis/TCA cycle
Glycogen synthase vs glycogen phosphorylase - is each activated or deactivated by phosphorylation?
Glycogen synthase- inhibited by phosphorylation
Glycogen phosphorylase- activated
During fed state, will glycogen synthase and phosphorylase be phosphorylated or not?
They will be dephosphorylated during fed state to promote glycogenesis
What signals muscle cells to break down glycogen
High AMP, epinephrine, Ca2+
Glucagon DOES NOT act on muscle
GSD 0
Deficiency in glycogen synthase
-Must eat frequently, hypoglycemic when fasting, muscle cramps due to lack of glycogen
GSD1/Von gierke
Deficiency in glucose-6-phosphatase
Inefficient release of free glucose into bloodstream by liver following gluconeogenesis/glycogenolysis
-Fasting hypoglycemia, lactic acidosis, hepatomegaly
GSD II/Pompe disease
Deficiency in acid maltase aka a-glucosidase
Impairs lysosomal glycogenolysis resulting in accumulation of glycogen in lysosomes
Disrupts normal function of liver/muscle cells
GSD III/Cori disease
Defective a-1,6-glucosidase debranching enzyme
-Patients have glycogen molecules with large number of short branches. Light hypoglycemia/hepatomegaly
GSD IV/Andersen
Defective glucosyl 4:6 transferase
-Long chain glycogen with fewer branches, hepatosplenomegaly, death by 5yrs
GSD V/Mcardle disease
Defective muscle glycogen phosphorylase
Unable to supply muscles with enough glucose, can’t break down glycogen. Reduce exercise
GSD VI/Hers disease
Defective liver glycogen phosphorylase
Hepatomegaly, low blood glucose
