Metabolism Lectures 1-2

Question 1

SGLT1

Answer 1

Glucose or galactose co-transporter with sodium. Does not transport fructose

Question 2

GLUT2

Answer 2

Insulin dependent with low affinity. High capacity for glucose and is bidirectional. Transports glucose out of intestine into bloodstream and into liver. Allows for sensing of glucose.

Question 3

GLUT4

Answer 3

Insulin Dependent transporter in MUSCLE, HEART and ADIPOCYTES. Higher affinity for glucose. Not active during a fasting state.

Question 4

Glycolysis 3 stages

Answer 4

Each stage occurs twice/glucose molecule making a total of 4 ATP.

*Takes place in the cytoplasm so NO NEED OF MITOCHONDRIA and active in all cell types

Stage I: Priming stage (Investment of 2 ATP).

Stage II: Splitting stage (Fructose 1,6 bisphosphate to Glyceraldehyde 3 phosphate or dihydroxyacetone phosphate)

Stage III: Oxidoreduction-phosphorylation stage/ stage earning (NADH, 2ATP, H2O).

Question 5

Glucose 6 phosphate trapping

Answer 5

Once glucose is made into G6P by hexokinase/glucokinase, it is trapped inside of the cell.

Question 6

Hexokinase/glucokinase

Answer 6

IRREVERSIBLE STEP (Uses ATP)

Catalyzes the first reaction in glycolysis which is the phosphorylation of glucose to make G6P

Question 7

Phosphofructokinase-1

Answer 7

IRREVERSIBLE STEP (Uses ATP)

highly regulated and makes Fructose -6-phosphate into Fructose-1,6- bisphosphate. Locks the glycolysis cycle.

Regulation: IN LIVER After a meal, Activated by fructose 2,6- bisphosphate (Made from fructose 6- phosphate via PFK-2). This causes glycolysis to move forward and to make Fatty acids

During starving, Glucagon inhibits PFK2. It is phosphorylated by PKA. Causes F26P levels to fall and PFK1 becomes less active.

When fed, Insulin activates phosphatase and they dephosphorylates PFK-2 so you have an increase in the F26P levels again which activates PFK1.

PFK2 acts as a kinase in the active state and a phosphorylase in the deactivated state*

Also inhibited by ATP and CITRATE in the MUSCLES.

Question 8

Pyruvate Kinase

Answer 8

IRREVERSIBLE STEP (Makes ATP)

activated by Fructose 1,6 bisphosphate and inhibited by alanine and phnosphorylation in liver during fasting by glucagon.

FASTING: Glucagon activates PKA which phosphorylates and inactivates pyruvate kinase.

inhibition of pyruvate kinase promotes gluconeogenesis.

Deficiency in pyruvate kinase leads to hemolytic anemia.

Question 9

Allosteric regulation

Answer 9

Activation or inhibition of an enzyme when a molecule or ligand binds to the enzyme and causes a conformational change.

Reversible and very quick and momentary

Question 10

Covalent modification (i.e. phosphorylation)

Answer 10

Phosphate group is bonded with a hydroxyl group on the enzyme. The negative charge causes a conformational change which changes the activity of the enzyme. (Phosphate removed by another enzyme: phosphatase).

Question 11

Hexokinase vs. Glucokinase

Answer 11

Hexokinase:

• Present in all cell types
• Non-inducible- present at all times
• Low-Km value (high affinity for glucose)- can’t handle high levels of glucose. Fully active even during fasting.
• High levels of fructose-6-pohsphate allosterically inhibit it.

Glucokinase:

• Present in liver and pancreas
• Inducible by high amounts of insulin. The insulin causes a translocation of the enzyme form the nucleus into the cytosol.
• High-Km value (low affinity for glucose)- can handle high levels of glucose. Very active right after meal.
• High levels of fructose-6-phosphate cause it to translocate into the nucleus

Question 12

Pyruvate Dehydrogenase

Answer 12

PDH converts pyruvate to acetyl-CoA which can then enter the TCA cycle. (Aerobic)

Deficiency would cause an increase in pyruvate and an increase in lactate in the system.

PDH is a multi enzyme complex (E1, E2, E3) that catalyzes the conversion of pyruvate to CoASH to Acetyl CoA.

NEEDS THE FOLLOWING VITAMINS TO ACT AS CO-FACTORS (Thiamine B1, Riboflavin B2, Niacin B3) if you have a deficiency in these enzymes the PDH is less active.

Question 13

Pyruvate carboxylase

Answer 13

Converts pyruvate to oxaloacetate. Replenishes the intermediates of the TCA cycle.

Deficiency would lead to an increase in pyruvate, lactate and alanine. You wouldn’t be able to go through the TCA cycle.

Question 14

Lactate dehydrogenase

Lactate sucks, your body doesn’t want lactate so it’s the last resort

Answer 14

Pyruvate reduced to form lactate (Anaerobic) Helps regenerate NAD+ so that glycolysis can go on. Last resort to do NAD+.

Aerobic respiration replaces the NAD+ through a metabolite shuttle system since NADH cannot cross the mitochondrial membrane.

If there is a LDH deficiency, then you are not able to go through glycolysis during anaerobic exercise.

Question 15

Pyruvate transamination

Answer 15

Converts pyruvate to alanine.

Question 16

Generation of NAD+

Answer 16

1) Lactate dehydrogenase
2) Malate-aspartate shuttle
3) Glycerol-phosphate shuttle

THE MITOCHONDRIAL MEMBRANE IS IMPERMEABLE TO NADH SO NEEDS A SHUTTLE

NADH produced in the cytosol by glycolysis can’t directly cross into the mitochondria membrane so the electrons are passed to the mitochondrial electron transport chain by the two shuttles.

Question 17

FADH2/NADH conversion to ATP

Answer 17

1 FADH2 = 1.5 ATP

1 NADH = 2.5 ATP

Question 18

Galactosemia

Answer 18

Deficiency of Galactokinase or Galactose 1-phosphate uridyltransferase (most common form).

Lactose in food = glucose + Galactose

if you have a deficiency in the enzymes you’re not able to convert the galactose into glucose 1- phosphate in order to go through glycolysis.

Question 19

Aldolase B deficiency

Answer 19

Can’t go through with glycolysis, you get a fructose accumulation since it’s the major step in the metabolism of fructose.

You cant cleave the fructose 1-phosphate so then you get a continuous accumulation of fructose 1-phosphate in the cell.