T02 - Carbohydrate Metabolism I

Question 1

Most dietary carbohydrates are in what form?

Answer 1

starch

Question 2

Starch comes in what three forms?

Answer 2

amylose; amylopectin (from plants); glycogen (from animals)

Question 3

Distinguish between amylose, amylopectin, and glycogen.

Answer 3

all are polymers of glucose but have different chemical linkages and branching patterns

Question 4

Describe the carbohydrate composition of an average/normal diet.

Answer 4

50% polysaccharides; 40% disaccharides; 10% monosaccharides

Question 5

What is cellulose?

Answer 5

an undigestable carbohydrate

Question 6

Where does carbohydrate digestion begin?

Answer 6

in the mouth, with amylase in the saliva

Question 7

Where does most carbohydrate digestion occur?

Answer 7

in the small intestine

Question 8

What is the major luminal enzyme for carbohydrate digestion in the small intestine?

Answer 8

amylase secreted from pancreas

Question 9

What are the three possible carbohydrate products following amylase action?

Answer 9

glucose; galactose; fructose

Question 10

(T/F) The epithelium of the GI tract can absorb mono-, di-, or polysaccharides.

Answer 10

False. It can only absorb monosaccharides, which means that disaccharides have to be further hydrolyzed.

Question 11

Polysaccharides must be hydrolyzed into monosaccharides in order to be absorbed by the epithelium of the GI tract. What happens if a polysaccharide can’t be broken down further?

Answer 11

remain in the GI tract where they exert osmotic force, preventing proper absorption of salt and water, and likely leading to diarrhea

Question 12

A critically important feature of absorption of substances across the epithelium is the requirement for

Answer 12

the epithelial cells to be polarized cells

Question 13

Describe the basic architecture of the system that transports monosaccharides across the GI epithelium.

Answer 13

two-step process involving sequential actions of apical membrane protein and basolateral membrane protein

Question 14

How are the monosaccharides glucose and galactose transported across the GI epithelium?

Answer 14

transported across apical surface by sodium-glucose-galactose transporter 1 (SGLT1) protein

transported across basolateral surface by GLUT2 through facilitated diffusion

Question 15

Describe the properties of the sodium-glucose-galactose transporter 1 (SGLT1) protein.

Answer 15

intrinsic apical membrane protein that couples active transport of either molecule with transport of Na⁺ ion

Question 16

The sodium-glucose-galactose transporter 1 (SGLT1) protein is an example of what kind of transport system?

Answer 16

SGLT1 is an example of a secondary active transport system (couples movement of one molecule, Na⁺, down its gradient to push another, glucose & galactose, against its gradient)

Question 17

How is the monosaccharide fructose transported across the GI epithelium?

Answer 17

absorbed by GLUT5, a distinct apical membrane protein, through facilitated diffusion

transported across basolateral surface by GLUT2 through facilitated diffusion

Question 18

What is the primary difference between facilitated diffusion and secondary active transport?

Answer 18

in facilitated diffusion, substances can only move down their gradients, but in secondary active transport, substances can be moved against their gradients if coupled to another molecule moving down its gradient

Question 19

What are the two classes of glucose transporters in mammalian cells?

Answer 19

Na⁺-dependent cotransporter

facilitated glucose transporter

Question 20

What are the high affinity glucose transporters?

Answer 20

GLUT-1 and GLUT-3 (low K_m, 1 mM)

Question 21

The GLUT-1 transporter is primarily found in (3)

Answer 21

erythrocytes [blood]

blood/brain barrier

cancerous cells

Question 22

What is the significance of the GLUT-3 transporter?

Answer 22

GLUT-3 transporter allows brain to have constant glucose levels, even when blood [glucose] fluctuates

Question 23

What is the low affinity glucose transporter?

Answer 23

GLUT2 (low affinity, K_m 17 mM)

Question 24

What does it mean for the GLUT2 transporter to be “high capacity?” How is this phenomenon important in terms of hormonal regulation?

Answer 24

rate of glucose import into liver and pancreatic beta cells is proportional to concentration of glucose in blood

allows insulin-producing pancreatic beta cells to “sense” blood levels and produce insulin accordingly

Question 25

How is the high K_m of the GLUT2 transporter important in hypoglycemic conditions?

Answer 25

high K_m for glucose (low affinity) means that when blood glucose is low, it's not imported into the liver and is instead preserved for more important organs like the brain

Question 26

Which tissues require insulin for glucose transport? Which tissues do **not** require insulin for glucose transport?

Answer 26

insulin required in **muscle** and **fat** tissue insulin not used in **liver** and **brain**

Question 27

What is the GLUT4 transporter?

Answer 27

insulin-dependent glucose transporter in muscle/fat tissue that translocates from cytosol to plasma membrane in response to insulin administration and facilitates uptake of glucose

Question 28

(T/F) Glucose can be stored as fat.

Answer 28

True. It can be stored as fat in adipose tissue, with the help of the GLUT4 transporter.

Question 29

Describe the K_m of the hexokinases (I-III) for glucose.

Answer 29

low K_m (0.01-0.05 mM), therefore high affinity

Question 30

Describe the distribution of the hexokinases (I-III) in the body.

Answer 30

wide tissue distribution

Question 31

What inhibits the hexokinases (I-III)?

Answer 31

glucose-6-phosphate (G6P) allosterically inhibits the hexokinases

Question 32

What is another name for hexokinase IV?

Answer 32

glucokinase

Question 33

Describe the K_m of glucokinase/hexokinase IV.

Answer 33

high K_m (10mM), so low affinity

Question 34

Describe the distribution of glucokinase/hexokinase IV.

Answer 34

limited tissue distribution, primarily found in liver, islets and pituitary

Question 35

(T/F) Glucose-6-phosphate is an inhibitor of all hexokinases.

Answer 35

**False.** G6P inhibits hexokinases I-III, but does _not_ inhibit hexokinase IV.

Question 36

The GLUT2 transporter is found in what tissues?

Answer 36

liver, pancreatic islets

Question 37

Write out the chemical equation for glycolysis.

Answer 37

Question 38

Draw out the steps of the glycolytic pathway. Identify the enzymes and cofactors associated with each step.

Answer 38

Question 39

What converts pyruvate to lactate? What are the associated cofactors?

Answer 39

lactate dehydrogenase catalyzes pyruvate → lactate (a reduction) associated: NADH → NAD⁺

Question 40

How can galactose be acquired?

Answer 40

synthesized from glucose obtained from diet (component of lactose)

Question 41

How is galactose transported across the apical surface from the lumen to the cell?

Answer 41

by a sodium-linked transporter (analogous to the Na/glucose co-transporter)

Question 42

What three enzymes are required for galactose utilization?

Answer 42

galactokinase uridylyl transferase UDP-galactose-4-epimerase

Question 43

Describe the role of galactokinase in galactose utilization.

Answer 43

phosphorylates carbon 1 of galactose in an ATP-consuming step

Question 44

How do galactokinase and hexokinase differ?

Answer 44

galactokinase phosphorylates carbon 1 of galactose, whereas hexokinase phosphorylates carbon 6 of glucose

Question 45

Describe the role of uridylyl transferase in galactose metabolism.

Answer 45

uridylyl transferase transfers UDP group from glucose to galactose-1-P to form glucose-1-P, which can then be used in glycolysis

Question 46

Describe the role of UDP-galactose-4-epimerase in galactose metabolism.

Answer 46

interconverts UDP-glucose and UDP-galactose in an NAD⁺-dependent reaction

Question 47

What explains why galactose is not essential in the diet?

Answer 47

UDP-galactose-4-epimerase can readily/easily interconvert UDP-glucose and UDP-galactose

Question 48

Draw out a diagram that illustrates galactose metabolism.

Answer 48

Question 49

Hereditary deficiencies for galactose metabolism mean that galactose and galactose-1-P accumulate in blood and tissues. How do cells respond to this accumulation, and what are the clinical consequences?

Answer 49

aldolase reductase reduces galactose → **galactitol** galactitol accumulate and cause damage to lens of eye (cataracts)

Question 50

Fructose is absorbed and metabolized by what tissue?

Answer 50

liver

Question 51

(T/F) Fructose is regulated by insulin.

Answer 51

**False**. In fact, excess fructose consumption has been hypothesized to cause insulin resistance.

Question 52

Why is fructose metabolism considered to be so "dangerous?"

Answer 52

pathway of fructose metabolism in liver _bypasses PFK_ (conversion of F-6-P into F-1,6-bP), a key regulatory step of glycolysis

Question 53

Draw a diagram outlining fructose metabolism in muscle.

Answer 53

Question 54

Draw a diagram outlining fructose metabolism in the liver.

Answer 54

Question 55

What is essential fructosuria?

Answer 55

uncommon autosomal recessive disorder involving fructose kinase deficiency

Question 56

What are the symptoms/pathological effects of essential fructosuria?

Answer 56

no pathological effects because kidney is capable of excreting excess fructose efficiently

Question 57

What causes hereditary fructose intolerance?

Answer 57

caused by deficiency in fructose-1-phosphate aldolase

Question 58

What are the symptoms of hereditary fructose intolerance? (3)

Answer 58

nausea vomiting failure to grow

Question 59

Ingestion of fructose in patients with hereditary fructose intolerance results in

Answer 59

severe hypoglycemia, linked to depletion of ATP and P_i

Question 60

What is the primary fuel source of RBCs?

Answer 60

glucose

Question 61

Which two tissues are responsible for gluconeogenesis?

Answer 61

liver kidney

Question 62

Redraw the pathway of glycolysis, showing the three distinct enzymes used for gluconeogenesis.

Answer 62

Question 63

Describe the allosteric effects of fructose-2,6-bisphosphate.

Answer 63

allosteric activator of PFK inhibitor of fructose-1,6-bisphosphatase

Question 64

Where is glucose-6-phosphatase located in the cell?

Answer 64

lumen of ER

Question 65

Glucose-6-phosphatase is ordinarily non-specific. What gives it specificity for G6P?

Answer 65

specificity conferred by G6P translocase in ER membrane

Question 66

What is the Cori cycle?

Answer 66

conversion of glucose to 3-carbon metabolites in extrahepatic tissues, and then regeneration of glucose from these metabolites in the liver

Question 67

Draw a diagram of the Cori cycle.

Answer 67

Question 68

What is the pathway for gluconeogenesis from fatty acids? Draw out the associated pathway.

Answer 68

Question 69

What two monosaccharides make up maltose?

Answer 69

maltose = glucose + glucose

Question 70

What two monosaccharides make up sucrose?

Answer 70

sucrose = glucose + fructose

Question 71

What two monosaccharides make up lactose?

Answer 71

lactose = glucose + galactose

Question 72

How is G6P shunted into the PPP?

Answer 72

converted to 6-PG, before going into PPP

Question 73

How is G6P shunted into glycogenesis or glycogenolysis?

Answer 73

first converted to G1P before being interconverted between those two cycles

Question 74

Which molecule is considered to be at the "center" of glucose utilization?

Answer 74

G6P

Question 75

Which molecule negatively regulates hexokinase?

Answer 75

glucose-6-phosphate (i.e. its own product)

Question 76

Which molecule serves as the major decision point for entry into glycolysis?

Answer 76

fructose-6-phosphate

Question 77

Which enzyme traps glucose in the cell?

Answer 77

hexokinase

Question 78

Which enzyme activates glucose for cleavage?

Answer 78

phosphofructokinase

Question 79

Which enzyme actually splits glucose?

Answer 79

aldolase

Question 80

Which enzymes harvest the energy of glucose through oxidoreduction and phosphorylation? (5)

Answer 80

G3P hydrogenase phosphoglycerate kinase phosphoglycerate mutase enolase pyruvate kinase

Question 81

What is an alternative fate for dihydroxyacetone phosphate?

Answer 81

can feed into fat

Question 82

Write out the net chemicalequation for glycolysis.

Answer 82

glucose + 2 ADP + 2 P_i → 2 pyruvate + 2 ATP + 2 NADH + 2 H₂O

Question 83

What are the four possible metabolic fates of pyruvate?

Answer 83

alanine (via transamination) oxaloacetate (via carboxylation) acetyl CoA (via oxidative decarboxylation) lactate (via reduction)

Question 84

Draw a diagram illustrating the fermentation of pyruvate in anaerobic conditions.

Answer 84

Question 85

What is the function of the pyruvate dehydrogenase (PDH) enzyme?

Answer 85

converts pyruvate into acetyl CoA

Question 86

Glucose *can* be synthesized from most amino acids. Is this process efficient?

Answer 86

**No**. Amino acids are not an efficient source to produce glucose.

Question 87

Among the fatty acids, which molecule is most efficient for glucose production?

Answer 87

odd-chain fatty acids

Question 88

Describe the regulatory effects of pyruvate kinase.

Answer 88

controls glycolysis vs. gluconeogenesis to prevent futile cycle

Question 89

Describe the regulatory effects of phosphofructokinase.

Answer 89

regulates amount of energy produced

Question 90

Glucokinase/hexokinase IV is regulated by

Answer 90

positively regulated by insulin

Question 91

Hexokinase (I-III) is regulated by

Answer 91

negatively regulated by G6P

Question 92

Describe the location of glucokinase in normoglycemic and hyperglycemic conditions.

Answer 92

normal conditions = glucokinase sequestered in nucleus by GK-RP hyperglycemic = dissociated from GK-RP and released into cytoplasm

Question 93

Which molecules negatively regulate phosphofructokinase? (3)

Answer 93

ATP (too much energy already, stop making pyruvate) citrate (too much energy already, stop making pyruvate) H+ (too much lactate, stop making pyruvate)

Question 94

What are the two possible states of pyruvate kinase?

Answer 94

phosphorylated inactive form dephosphorylated active form

Question 95

What molecule allosterically activates pyruvate kinase?

Answer 95

fructose-1,6-bisphosphate

Question 96

What molecules allosterically inhibit pyruvate kinase? (2)

Answer 96

ATP alanine

Question 97

Describe the activity of pyruvate kinase in hypo- and hyperglycemic conditions.

Answer 97

hypoglycemic = pyrvuate kinase inactive (phosphorylated by protein kinase A) hyperglycemic = pyruvate kinase active (dephosphorylated by phosphoprotein phosphatase)

Question 98

Where in the cell is the pyruvate carboxylase enzyme located?

Answer 98

mitochondria

Question 99

PEP carboxykinase is activated by

Answer 99

CREB, a hormonal regulated transcription factor

Question 100

What enzyme serves as the rate limiting step of gluconeogenesis?

Answer 100

fructose-1,6-bisphosphatase

Question 101

What molecule activates fructose-1,6-bisphosphatase?

Answer 101

citrate

Question 102

Write out the pathway of PFK-2/FBPase-2 activity in fasting conditions.

Answer 102

Fasting → glucagon → ↑ cAMP → ↑ PKA → active FBPase-2 → ↓ Fructose-2,6-BP → inactive PFK-1 → gluconeogenesis

Question 103

Write out the pathway of PFK-2/FBPase-2 activity in fed conditions.

Answer 103

Fed → insulin → dephosphorylation → active PFK-2 → ↑ Fructose-2,6-BP → active PFK-1 → glycolysis

Question 104

Which two amino acids cannot serve as substrates for glucose production?

Answer 104

lysine leucine

Question 105

Summarize the key (i.e. rate-determining) enzyme of glycolysis and its associated regulators.

Answer 105

PFK-1 activated by AMP and F-2,6-bP inhibited by ATP, H⁺, citrate

Question 106

Summarize the key (i.e. rate-determining) enzyme of gluconeogenesis and its associated regulators.

Answer 106

F-1,6-bPase activated by F-1,6-bP and citrate inhibited by AMP and F-2,6-bP