Carbohydrate Metabolism

Question 1

GLUT1

Answer 1

Ubiquitous but high in RBCs and Brain, Km 1mM

Question 2

GLUT2

Answer 2

Liver and Pancreas, Km 10mM

Question 3

GLUT3

Answer 3

Neurons, Km 1mM

Question 4

GLUT4

Answer 4

INSULIN DEPENDENT, skeletal muscle, adipose tissue, and heart, Km 5mM. Insulin signaling causes fusion of vesicles with plasma membrane and enables glucose uptake.

Question 5

Net Yield of Glycolysis

Answer 5

2 ATP, 2 NADH, and 2 pyruvate

Question 6

Irreversible Steps of Glycolysis

Answer 6

Hexokinase/Glucokinase, Phosphofructokinase 1, Pyruvate Kinase

Question 7

Steps that require ATP for Glycolysis

Answer 7

Glucose -> Glucose-6-Phosphate

Fructose-6-Phosphate -> Fructose-1,6-bisphosphate

Question 8

Steps that generate NADH for glycolysis

Answer 8

Glyceraldehyde 3-phosphate + NAD+ -> 1,3-bisphosphoglycerate + NADH X 2 via G3P dehydrogenase

Question 9

Steps that generate ATP for Glycolysis

Answer 9

1,3 bisphosphoglycerate -> 3 phosphoglycerate + ATP X 2

Phosphoenolpyruvate -> Pyruvate X 2

Question 10

Rate Limiting Enzyme of Glycolysis and explain

Answer 10

Phosphofructose Kinase 1, Insulin activates Protein phosphatase to dephosphorylate PFK-2. Activated PFK-2 can then convert F6P to F-2,6-BP, which can then activate PFK1 to convert F6P to F-1,6-BP.

Question 11

Regulation of Pyruvate Kinase

Answer 11

Insulin activates protein phosphatases that dephosphorylates PK to activate it. Also activated by F-1,6-BP and insulin and is inhibited by ATP, Alanine, and glucagon. High glucagon and high cAMP activate protein kinase A, that phosphorylated PK to inactivate it.

Question 12

RBCs and Glycolysis disorders

Answer 12

Since RBCs lack mitochondria, glycolysis is only mechanism for producing ATP. Failure of glycolysis results in ATP deficiency and leads to destruction of RBCs aka hemolytic anemia.

Question 13

Brain and Glucose relationship

Answer 13

Glucose is one of the only fuel molecule that can cross blood brain barrier. During starvation, brain cells obtain glucose from liver via gluconeogenesis. The brain can also utilize ketone bodies for fuel during excessive starvation.

Question 14

Carbohydrate metabolism in fed vs fasting state

Answer 14

Fed state: abundant glucose, release of insulin causes glucose uptake by hexokinase/glucokinase and prodction of glycogen and decreased gluconeogenesis. Fasting state: low glucose, release of glucagon and epinephrine. increase on gluconeogenesis and glyocogenolysis.

Question 15

Diabetes

Answer 15

Characterized by hyperglycemia. Type 1: severe insulin deficiency due to loss of pancreatic beta cells from autoimmune destruction.
Type 2: insulin resistance that progresses to loss of beta cells function

Question 16

Hemolytic Anemia

Answer 16

Results from premature destruction of RBCs from causes such as defects in glycolytic enzymes such as phosphoglucose isomerase, triosephosphate isomerase, and pyruvate kinase (most common).

Question 17

GSD VII

Answer 17

Tarui disease, deficiency in PFK-1 results in exercise-induced muscle cramps, hemolytic anemia, etc.

Question 18

Whole body needs of glucose daily?
Daily glucose requirement for brain?
Glucose present in bodily fluids?
Glucose readily available from glycogen?

Answer 18

160 g/day
120 g/day
20 g
190 g

Question 19

Where does gluconeogenesis occur?

Answer 19

Liver, kidney, and small intestine

Question 20

Irreversible steps of gluconeogenesis? Activators and inhibitors of each enzyme

Answer 20

Pyruvate -> OAA (Malate OAA shuttle) via pyruvate carboxylase (in mitochondria). Acetyl CoA activates and ADP inhibits.
OAA -> PEP via PEP carboxykinase. Activated by cortisol, glucagon, and thyroxine.
F-1,6,BP -> F6P via F-1,6-bisphosphatase (rate limiting step). Glucagon activates PKA, which phosphorylates PFK2 to inhibit it and stimulates FBPase2 to convert F26BP back to F6P.
Glucose 6P -> Glucose 6 phosphatase.

Question 21

Cori Cycle

Answer 21

Links the lactate produced from anaerobic glycolysis in RBC and exercising muscle to gluconeogenesis in liver

Question 22

Precursors of Gluconeogenesis, sources, and point of entry for each

Answer 22

Glycerol, lipid degradation, and DHAP
Propionate, degradation of odd-numbered FA, TCA cycle
Alanine, protein degradation, pyruvate
AA, protein degradation, TCA cycle intermediates

Question 23

Disorders of Gluconeogenesis

Answer 23

F1,6BP deficiency developed from mutation in this enzyme. Presents in infancy or early childhood

Question 24

GSD1a

Answer 24

Von Gierke Disease (autosomal recessive): Deficiency in G6P, patients exhibit marked fasting hypoglycemis, lactic acid

Question 25

Fructose uptake is via what transporter?

Galactose/Glucose uptake via what?

Answer 25

GLUT 5

SGLT1

Question 26

Fanconi-Bickel Syndrome

Answer 26

Inherited deficiency of GLUT2 in the liver, pancreatic beta cells, and PCT. Unable to take up glucose, fructose, and galactose.

Question 27

Sorbitol accumulation defect

Answer 27

Glucose is reduced to sorbitol by aldose reductase.
Sorbitol oxidized to fructose by sorbitol dehydrogenase
Cells that lack sorbitol dehydrogenase can accumulate sorbitol, which triggers water influx and cause swelling. Manifests as retinopathy and cataracts.

Question 28

Fructose entry points into glycolysis

Answer 28

Fructose can be converted to F6P and enter straight away of it can be converted to F1P and then glyceraldehyde, which can go to G3P and DHAP. High fructose corn syrup is bad because fructose can bypass PFK1

Question 29

Galactosemia

Answer 29

Deficiency in glucose 1P uridyltransferase (GALT), leads to accumulation of galactitol.
Deficiency in galactokinase, can lead to cataracts in early infancy.

Question 30

Oxidative steps of PPP

Answer 30

G6P -> Ribulose 5 P and creates 2 NADPH molecules. Rate limiting step is G6P dehydrogenase. G6PD deficiency can cause hemolytic anemia and NADPH is important for phagocytic cells for antioxidant power of glutathione reductase.

Question 31

Non oxidative Phase of PPP

Answer 31

Generates Ribose-5P , G3P, and fructose 6P

Question 32

Which cells require a high demand of ribose 5P?

Which cells require a high demand for NADH?

Answer 32

Rapidly dividing cells need ribulose 5P for RNA synthesis

Phagocytic cells require PPP due to NADPH for antioxidants.

Question 33

Structure of glycogen

Answer 33

Glucose molecules linked together via a(1,4)-glycosidic bond and branch points formed via a-1,6 glycosidic bonds. Non reducing ends have free OH group at C4 and reducing ends are connected to glycogenin.

Question 34

Where is glycogen stored?

Difference between liver and muscle glycogen?

Answer 34

Glycogen stored in liver, muscle, and other tissues and stored as granules.
Liver Glycogen - regulates blood glucose levels
Muscle glycogen - provides reservoir of fuel for physical activity.

Question 35

Rate limiting step for Glycogenesis?

Answer 35

Glycogen synthase, which catalyzes the transfer of glucose from UDP-glucose to non-reducing end via a-1,4 glycosidic bond.

Question 36

Branching enzyme of Glycogenesis?

Answer 36

When glycogen reaches around 11 residues, glucosyl (4:6) transferase reaches monomers a-1,6 bond.

Question 37

Rate limiting step for Glycogenolysis?

Answer 37

Chain shortening done by glycogen phosphorylase (GP), which reduces glucose-1-P from the non-reducing ends of glycogen. Uses pyridoxal phosphate (Vitamin B6) as cofactor.

Question 38

Debranching transfer enzyme for glycogenolysis?

Answer 38

transferase (4:4) activity to transfer a block of 3 of the remaining 4 glucose to the non reducing end forming an a-1,4-bond. Then it cleaves the a-1,6 bond of the single remaining glucose.

Question 39

GSD II

Answer 39

Pompe disease, deficiency in enzyme a-1,6 glucosidase (acid maltase) -> won’t be able to release terminal glucose and break down of glycogen would not be possible.

Question 40

Activated forms of Glycogen synthase and Glycogen phosphorylase? Inactive form?

Answer 40

When both are P = GS is inactive and GP is active

When both are deP = GS is active and GP is inactive

Question 41

Glucagon does NOT act on what?

Answer 41

Muscle

Question 42

4 key proteins involved in regulation of insulin?

Answer 42

GLUT4, PKB, PP1, and GSK3

Question 43

Type 2 Diabetes

Answer 43

reduced sensitivity to insulin

Blood glucose criteria : >126 mg/dl fasting or >199 mg/dl fed

Question 44

Keys enzymes and second messengers affected by glucagon?

Answer 44

G Protein, AC and cAMP, PKA, PP1, PK

Question 45

GSD 0
GSD II
GSD IV
GSD V
GSD VI

Answer 45

0 = -, glycogen synthase, glycogenesis: chain elongation
II= Pompe disease, acid maltase, lysosomal glycogenolysis: release of glucose
IV = Andersen disease, glucosyl (4:6) transferase, Glycogenesis: chain branchinh
V: McArdle disease: muscle glycogen phosphorylase, Glycogenolysis: Glc 1-p release
VI: Hers disease: liver glycogemn phosphporylase, Glycogenolysis: Glc 1-p release