Chapter 12: Glycolysis and Pyruvate Dehydrogenase Flashcards
Name the complex forms of which most of our food is found in?
forms such as starch (amylose and amylopectin) and the disaccharides sucrose and lactose
What enzyme in the mouth starts breakdown of starch?
salivary amylase randomly hydrolyses the starch polymers to dextrins
In the intestines dextrins are hydrolyzed to what disaccharides?
maltose and isomaltose
Maltase cleaves maltose into what monosaccharides?
2 glucoses
Isomaltase cleaves isomaltose to what monosaccharides?
2 glucoses
Lactase cleaves lactose to what monosaccharides?
glucose and galactose
Sucrase cleaves sucrose to what monosaccharides?
glucose and fructose
What transporter takes up glucose into the mucosal cells?
GLUT
What is the normal glucose concentration in peripheral blood?
4-6 mM (70-110 mg/dL)
In the pancreas what serves as the glucose sensors?
GLUT 2 along with glucokinase
GLUT 4 translocation to the cell membrane in skeletal muscle is stimulated by exercise. This effect, is independent of insulin and involves what enzyme?
5’AMP activated kinase
What tissues is GLUT 1 found in?
Most tissue (brain, red cells)
What tissues is GLUT 2 found in?
Liver and pancreatic B-cells
What tissues is GLUT 3 found in?
Most tissues
What tissues is GLUT 4 found in?
skeletal muscle and adipose tissue
Which GLUT receptor has insulin-stimulated glucose uptake, stimulated by exercise in the skeletal muscle
GLUT 4
Insulin secretion by pancreatic B-cells is biphasic. What is meant by this statement?
glucose stimulates the first phase (within 15 minutes) with release of preformed insulin. The second phase (several hours) involves insulin synthesis at the gene level.
What is the rate limiting enzyme and main control point of glycolysis?
PFK-1
Which has the higher Km glucokinase or hexokinase
glucokinase
Where is glucokinase primarily found?
in hepatocytes and pancreatic B-cells along with GLUT-2, acts as the glucose sensor
Insulin stimulates and glucagon inhibits PFK-1 in hepatocytes by an indirect mechanism involving what?
PFK-2 and fructose 2,6 bisphosphate (F2,6-BP)
How does insulin activate PFK-2?
activates it via the tyrosine kinase receptor and activation of phosphatases, which converts a tiny amount of fructose 6- phosphate to fructose 2,6 bisphosphate (F2,6-BP) which in turn activates PFK-1 leading to stimulation of glycolysis
How does glucagon inhibit PFK 2?
via cAMP dependent protein kinase A lowering F2,6-BP and thereby inhibiting PFK-1
How can arsenate lead to death?
arsenate inhibits the conversion of glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate by mimicking phosphate in the reaction. The arsenate-containing product is water labile enabling glycolysis to proceed but resulting in no ATP production
Near complete deficiency of glucokinase activity is associated with what condition?
neonatal type 1 diabetes.
Mutations which increase the Km of glucokinase can cause what condition/ symptoms?
decreasing the affinity for glucose are associated with some cases of maturity-onset diabetes of the young (MODY)
hypoinsulinemia and hyperglycemia
Mutations which decrease the Km of glucokinase (increasing the affinity for glucose)?
hyperinsulinemia and hypoglycemia
What does DHAP stand for?
dihydroxyacetone phosphate
What is the function of DHAP?
used in liver and adipose tissue for triglyceride synthesis
electron shuttle metabolite
3 enzymes in the glycolysis pathway catalyze reactions that are irreversible. What are they?
glucokinase/hexokinase
PFK-1
pyruvate kinase
What is C-peptide?
a short polypeptide that connects the A chain to the B[chain in the proinsulin molecule. It is removed after proinsulin is packaged into vesicles in the Golgi
How much energy products are produced by anaerobic glycolysis?
2 ATP/glucose
How much energy is produced from aerobic glycolysis? (in cytoplasm)
2ATP/glucose plus 2 NADH/glucose
Cytoplasmic NADH oxidized using the malate shuttle produces mitochondrial NADH and yields how much ATP?
3ATP by oxidative phosphorylation
Cytoplasmic NADH oxidized by the glycerol phosphate shuttle produces mitochondrial FADH2 and yields approximately how much ATP?
2 ATP by oxidative phosphorylation
In RBC anaerobic glycolysis represents the only pathway for ATP production yielding how much ATP?
2 ATP/glucose
Draw out the glycolysis pathway.
Draw out diagram
What is the enzyme found in the erythrocytes that produces 2,3 BPG from 1,3 BPG in glycolysis?
Biphosphoglycerate mutase
Which chains does 2,3 BPG bind to in HbA?
2,3 BPG binds to the β-chains of HbA
Why can 2,3 BPG not bind to HbF well?
HbF has a higher affinity for O2 and only binds to β subunit which isn’t found in HbF
What are the chain (subunits) that comprise HbF?
α2γ2
What is the second most common genetic deficiency that causes hemolytic anemia?
pyruvate kinase deficiency
What is the most common genetic deficiency which causes hemolytic anemia?
G6PDH (glucose 6-phosphate dehydrogenase)
What are the characteristics of pyruvate kinase deficiency?
- chronic hemolysis
- increased 2,3 BPG and therefore a lower than normal O2 affinity of HbA
- Absence of Heinz bodies (Heinz bodies are more characteristic of G6PD deficiency
Why does pk deficiency in the RBC lead to hemolysis?
anaerobic glycolysis is only way for RBC to produce ATP because no mitochondria
Decrease in ATP causes erythrocyte to lose its characteristic biconcave shape and signals its destruction in spleen
Decreased ion pumping by Na+/K+ ATPase results in loss of ion balance and causes osmotic fragility, leading to swelling and lysis
Why is transfused blood not as good at delivering O2 to peripheral tissues?
has lower than expected 2,3 BPG
What is the meaning of P50?
Pressure @ which hemoglobin is 50% saturated
What are conditions that create a Bohr effect?
anything that shifts the O2/Hb curve to the right
Inc. CO2
Inc. H+
Inc. T
Inc. 2,3 BPG
Inc P50
What is a the meaning of shift to the right on the O2/Hb dissociation curve?
means there is a dec. affinity for O2(Hb) bond and therefore more unloading of O2
What are conditions that create a haldane effect?
dec. CO2
dec. H+
dec. 2,3 BPG
dec. T
dec P50
What is the meaning of a left shift on the O2/Hb dissociation curve?
means higher affinity of Hb for O2 and less unloading of O2
Be able to draw out the flow in Galactose metabolism.
Draw out diagram
What are the symptoms of lactase deficiency after ingestion of lactose (milk products)?
diarrhea
bloating
cramps
What are the symptoms of galactokinase deficiency?
cataracts early in life
What are the symptoms of Gal 1-P uridyltransferase deficiency?
- cataracts early in life
- vomiting, diarrhea following lactose ingestion
- lethargy
- liver damage, hyperbilirubinemia
- intellectual disability
Can administration of galactose during hypoglycemia be used to increase blood glucose?
yes
In the well-fed state, galactose can enter glycolysis and lead to storage of what?
glycogen storage
Where is lactase present?
associated with brush border membrane of the small intestine