Glycogen, Gluconeogenesis, and the Hexose Monophosphate Shunt

Question 1

Glycogen core protein

Answer 1

Glycogenin

Question 2

Activated form of glucose that is ready for addition to the glycogen chain

Answer 2

UDP-glucose (G6P to G1P to UDP-glucose)

Question 3

Rate limiting enzyme of glycogen synthesis

Answer 3

Glycogen synthase (alpha-1,4)

Question 4

Activator of Glycogen synthase

Answer 4

Insulin

Question 5

Inhibitors of Glycogen synthase

Answer 5

Glucagon (only in the liver), Epinephrine

Question 6

Another name for the Branching Enzyme

Answer 6

Glycosyl alpha-1,4:alpha-1,6 Transferase

Question 7

Rate limiting enzyme in Glycogenolysis

Answer 7

Glycogen phosphorylase (G-6-P to free Glucose)

Question 8

Activators of Glycogen phosphorylase

Answer 8

Liver: Epinephrine, Glucagon; Skeletal Muscle: Epinephrine, AMP, Ca (high AMP and Ca signals an active muscle contraction and tells the muscle that it needs energy)

Question 9

Inhibitors of Glycogen phosphorylase

Answer 9

Liver: Insulin; Skeletal Muscle: Insulin, ATP (presence of ATP tells the muscle to stop breaking down glycogen because there’s energy already)

Question 10

Enzyme capable of hydrolyzing alpha-1,6-glycosidic bonds

Answer 10

Debranching enzyme (glucosyl alpha-1,4:alpha-1,4 transferase and alpha-1,6 glucosidase)

Question 11

Severe hypoglycemia, lactic acidosis, hepatomegaly, hyperlipidemia, hyperuricemia, short stature doll-like facies, protruding abdomen, emaciated extremities

Answer 11

Von Gierke (Type I) disease; Substitution of galactose or fructose, or administration of glucagon or epinephrine won’t help.

Question 12

Deficient enzyme in Von Gierke Disease

Answer 12

Glucose-6-phosphatase (sequesters free glucose from G-6-P)

Question 13

Deficiency in Branching enzyme. Also called Amylopectinosis.

Answer 13

Andersen Disease, Type IV (Infantile hypotonia, cirrhosis, death by 2 years)

Question 14

Deficient enzyme in McArdle Disease (Muscle cramps, weakness on exercise, myoglobinuria)

Answer 14

Muscle glycogen phosphorylase/Myophosphorylase (breaks alpha-1,4 glycosidic bonds to free up the G-1-Ps); Drinking sucrose-containing drink will help (provision of dietary glucose)

Question 15

Type III Glycogen storage disease

Answer 15

Cori Disease (Mild hypoglycemia, liver enlargement due to Debranching Enzyme deficiency). Hypoglycemia is mild only because they can still get glucose from straight chains.

Question 16

Deficiency in Hepatic Glycogen phosphorylase

Answer 16

Hers Disease, Type VI (Mild fasting hypoglycemia, hepatomegaly, cirrhosis). Hypoglycemia is mild because liver is capable of gluconeogenesis plus they can still get glucose from the muscle, but the liver is crowded by unutilized glycogen.

Question 17

Massive cardiomegaly, muscle weakness, death by 2 years, deficiency in Lysosomal alpha-1,4-glucosidase (aka acid maltase)

Answer 17

Pompe Disease; Glycogen-like inclusion bodies (prominent lysosomes with clusters of electron-dense granules).

Question 18

Substrates for gluconeogenesis

Answer 18

G3P (from TAGs in adipose), lactate, amino acids (gluconeogenic) from muscle protein

Question 19

Ketogenic amino acids

Answer 19

Leucine and lysine

Question 20

Amino acids that are both ketogenic and glucogenic

Answer 20

Phe Ile Trp Tyr Thr (PutangIna may tatlong Tite = PI! TTT!)

Question 21

Major gluconeogenic amino acid in the body

Answer 21

Alanine (converted to pyruvate by ALTs, also the enzyme tested to assess hepatocyte damage)

Question 22

Mitochondrial enzyme that converts Pyruvate to OAA

Answer 22

Pyruvate carboxylase (carboxylase enzymes require Biotin)

Question 23

Deficiency in this vitamin, usually caused by ingestion of raw egg whites (avidin) and long-term home TPN

Answer 23

Biotin Deficiency (alopecia, scaly dermatitis, waxy pallor, and mild acidosis)

Question 24

After shuttling OAA from the mitochondria to cytoplasm via the Malate shuttle, OAA is converted to PEP by

Answer 24

PEP Carboxykinase (PEPCK)

Question 25

Hormones that induce PEPCK

Answer 25

Glucagon, Cortisol

Question 26

Rate limiting enzyme in Gluconeogenesis, which is the arch nemesis of PFK (the rate-limiting enzyme in Glycolysis)

Answer 26

Fructose-1,6-bisphosphatase. It is activated by ATP, and inhibited by AMP and F-2,6-BP (Recall that F-2,6-BP is increased by Insulin and decreased by Glucagon)

Question 27

Location of Glucose-6-phophatase

Answer 27

Lumen of the endoplasmic reticulum of LIVER

Question 28

Gluconeogenesis is dependent on this metabolic pathway (because this pathway provides ATP consumed in gluconeogenesis)

Answer 28

Beta-oxidation of fatty acids

Question 29

The two major mitochondrial enzymes that use pyruvate (one is catabolic, one is anabolic)

Answer 29

Pyruvate dehydrogenase and pyruvate carboylase (biotin). BOTH are regulated by the amount of Acetyl CoA

Question 30

Cori cycle is

Answer 30

Lactate from RBC/exercising muscle is converted in the liver to Glucose, and this Glucose is returned back to RBC/muscle for consumption

Question 31

Alanine cycle is

Answer 31

Alanine released from muscle is used for gluconeogenesis (pyruvate) and urea synthesis (amino group)

Question 32

High NADH environment caused by Alcoholism favors formation of

Answer 32

Lactate (from pyruvate), Malate (from OAA), and G3P (from DHAP)

Question 33

Metabolism of alcohol to acetate yields how many NADH

Answer 33

2 (one from alcohol DH and another from acetaldehyde DH)

Question 34

Pathogenesis of alcoholic fatty liver

Answer 34

High NADH > very slow beta-oxidation despite hypoglycemia > FFAs continually released from adipose for supposed gluconeogenesis in liver > due to slow beta-ox, accumulation of FFAs in the liver instead > Presence of High G3P (High NADH favors conversion of DHAP to G3P) binds to the accumulated FFAs = triglycerides inappropriately formed in liver

Question 35

Two major functions of Hexose Monophosphate Shunt/Pentose Phosphate Pathway

Answer 35

NADPH production (for oxidative burst), and Ribose-5-P production (for nucleotide synthesis)

Question 36

Rate-limiting enzyme in PPP/HMS

Answer 36

G-6-P Dehydrogenase (G6P to 6-Phosphogluconate), induced by Insulin

Question 37

The only Thiamine enzyme in RBCs, responsible for interconversion of the pentoses in PPP

Answer 37

Transketolase

Question 38

Substrate responsible for maintaining a supply of reduced Glutathione; reduces oxidized glutathione via Glutathione Reductase

Answer 38

NADPH

Question 39

Heinz bodies result from

Answer 39

Hemoglobin denaturation (due to peroxide accumulation in G6PD)

Question 40

G6PD patients are not susceptible against what parasite/disease (believed to be an evolutionary adaptation in endemic countries)

Answer 40

Plasmodium / Malaria

Question 41

Genetic deficiency in NADPH oxidase in the PMNs. Negative nitroblue tetrazolium test.

Answer 41

Chronic granulomatous disease (CGD), susceptibility to catalase-positive organisms, S. aureus, Kleb, E.coli, Candida, Aspergillus

Question 42

Glycogenolysis happens in the

Answer 42

Cytoplasm

Question 43

Most common genetic cause of hemolytic anemia

Answer 43

G6PD Deficiency