Metabolism I

Question 1

What are converted to high energy ATPs to provide energy for cells and tissues?

Answer 1

• glucose
• FA
• AA

Question 2

Sources of ATP

Answer 2

• Adenylate kinase
• Creatine phosphokinase/phosphocreatine (CPK)
• Anaerobic metabolism
• Aerobic metabolism

Question 3

Glycolysis

Answer 3

breakdown of 1 molecule of glucose (6C) into 2 molecules of pyruvate (3C)

Question 4

Where does glycolysis occur?

Answer 4

Cytoplasm

Question 5

How many steps are there in glycolysis?

Answer 5

10 steps

Question 6

Major points in glycolysis

Answer 6

glucose –> C6P –> pyruvate –> acetyl CoA

Question 7

Three enzymes of glycolysis

Answer 7

• hexokinase (HK)
• PFK
• PK

Question 8

Where does pyruvate go after glycolysis

Answer 8

• Lactate (PDH pathway)

- acetyl CoA –> TCA cycle (PDH pathway)

Question 9

How many stages is glycolysis broken into?

Answer 9

3

Question 10

Where does the formation of acetyl CoA occur?

Answer 10

mitochondria

Question 11

What enzyme is responsible for pyruvate conversion to acetyl CoA?

Answer 11

Pyruvate dehydrogenase complex

Question 12

How many ATP are generated when converting pyruvate into acetyl CoA?

Answer 12

2 ATP

Question 13

Where does the Kreb’s cycle occur?

Answer 13

Mitochondria

Question 14

What does the Kreb’s cycle depend on?

Answer 14

availability of substrates and cofactors

Question 15

How many ATP molecules are produced from glucose by aerobic respiration?

Answer 15

36 ATP

Question 16

What is the net energy of ATP from glycolysis?

Answer 16

2 ATP

Question 17

What is the net energy of ATP from Kreb’s cycle

Answer 17

32 ATP

Question 18

What regulates glycolysis?

Answer 18

• Hexokinase

- Glucokinase

Question 19

How many isoforms of hexokinase are present?

Answer 19

4

I, II, III and IV

Question 20

What is HK IV called?

Answer 20

glucokinase

Question 21

Where are HK I - III found?

Answer 21

in most tissues

Question 22

HK I - III Km

Answer 22

Low Km for glucose relative to its concentration in blood

Question 23

What is HK I - III inhibited by?

Answer 23

Strongly inhibited by G6P

Question 24

Where is HK IV found?

Answer 24

liver and pancreas

Question 25

HK IV and Km

Answer 25

high KM for glucose

Question 26

HK IV inhibition

Answer 26

less sensitive to inhibition by G6P

Question 27

What is glucokinase regulated by?

Answer 27

- F6P | - fructose

Question 28

GK inhibitory protein

Answer 28

- GK-RP | - sequesters GK as an inactive complex in nucleus

Question 29

Where is GK-RP found?

Answer 29

nucleus of liver cells

Question 30

What promotes the binding of GK to GK-RP?

Answer 30

F6P

Question 31

What inhibits GK?

Answer 31

F6P

Question 32

How is F6P inhibition of GK overcome?

Answer 32

by large increase in glucose concentration

Question 33

Fructose and GK

Answer 33

- fruits - vegetables - high fructose corn syrup

Question 34

What does fructose get converted to?

Answer 34

F1P

Question 35

What activates GK?

Answer 35

F1P

Question 36

Role of F1P

Answer 36

- promotes hepatic glucose utilization | - partly responsible for adverse effects of fructose consumption (lipogenesis, hypertriglyceridemia etc)

Question 37

GK as an enzyme

Answer 37

inducible

Question 38

What stimulates GK transcription?

Answer 38

Insulin

Question 39

What can a mutation in GK lead to?

Answer 39

a form of MODY

Question 40

What does PFK1 catalyze?

Answer 40

the first committed step in glycolysis

Question 41

What are the negative effectors of PFK1?

Answer 41

ATP Low pH Citrate

Question 42

What are the positive effectors of PFK1?

Answer 42

AMP (cAMP) | F2,6BP

Question 43

What inhibits PFK1?

Answer 43

ATP (negative allosteric effector)

Question 44

What promotes PFK1 activity?

Answer 44

AMP (positive allosteric effector)

Question 45

What does F1,6 BP'ase catalyze?

Answer 45

an irreversible reaction opposite to that catalyzed by PFK1

Question 46

What doe PFK1 and F1-6BP'ase together catalyze?

Answer 46

futile cycle

Question 47

What inhibits F1,6 P'ase?

Answer 47

AMP

Question 48

What does the inhibition of F1,6 P'ase lead to?

Answer 48

- increased F1, 6BP | - glycolytic flux

Question 49

What is PFK1 regulated by?

Answer 49

- intracellular pH - citrate - H + ions

Question 50

What is PFK1 not regulated by?

Answer 50

Lactic acid (the end product of glycolysis)

Question 51

What do some tissues prefer as fuels instead of glucose?

Answer 51

FA and ketone bodies

Question 52

Why do some tissues prefer FA and ketone bodies over glucose?

Answer 52

to spare glucose for use by organs which specifically require glucose for energy (brain)

Question 53

What does citrate inhibit?

Answer 53

PFK1 | - thus glucose utilization

Question 54

Where does citrate accumulate?

Answer 54

in cytosol

Question 55

What inhibits glycolysis?

Answer 55

Glycogen | Epinephrine

Question 56

What is a positive allosteric effector of PFK1?

Answer 56

F2,6P

Question 57

What happens if there if no F2, 6P?

Answer 57

glycolysis cannot occur in liver

Question 58

What triggers adenylate cyclase through cAMP?

Answer 58

binding of glucagon to its receptor triggers

Question 59

What does adenylate cyclase through cAMP cause?

Answer 59

decrease in F2, 6P

Question 60

What does a decrease in F2, 6P lead to?

Answer 60

- reduces PFK1 - activates F1, 6BPase - inhibit glycolysis

Question 61

F1, 6P and glycolysis

Answer 61

intermediate via PFK1

Question 62

F2, 6P and glycolysis

Answer 62

side product via PFK2

Question 63

What does F2,6BPase oppose?

Answer 63

PFK2 bi-functional enzyme - same protein

Question 64

What inactivates kinase?

Answer 64

Phosphorylation

Question 65

What activates phosphatase activity?

Answer 65

phosphorylation

Question 66

What activates kinase?

Answer 66

dephosphorylation

Question 67

What inactivates phosphatase activity?

Answer 67

dephosphorylation

Question 68

What regulates glycolysis?

Answer 68

- PK

Question 69

What inhibits PK?

Answer 69

physiological concentration of ATP

Question 70

What activates PK?

Answer 70

F1, 6BP

Question 71

Is PK active or inactive in the phosphorylated state?

Answer 71

inactive

Question 72

Is PK active or inactive in the dephosphorylated state?

Answer 72

active

Question 73

What causes a change in activity of PK?

Answer 73

covalent modification by PKA

Question 74

What is PK induced by?

Answer 74

- high carbohydrate intake - high insulin levels - in liver

Question 75

Glycogen synthase

Answer 75

- converts glucose to glycogen - insulin promotes glycogen synthesis - fed state

Question 76

Glycogen phosphorylase

Answer 76

- breakdown glycogen to glucose - glucagon promotes glycogen breakdown - fasted state

Question 77

When is glycogen synthase active?

Answer 77

fed state

Question 78

When is glycogen phosphorylase active?

Answer 78

fasted state

Question 79

Gluconeogenesis

Answer 79

formation of new sugar

Question 80

When is gluconeogeneis activated?

Answer 80

- fasting condition | - during exercise

Question 81

What promotes gluconeogenesis?

Answer 81

Glucagon to protect against hypoglycemia

Question 82

What does gluconeogenesis provide glucose for?

Answer 82

brain muscles erythrocytes

Question 83

Where does gluconeogenesis take place?

Answer 83

- mainly in liver | - small extent renal cortex

Question 84

What are the precursors for gluconeogensis?

Answer 84

- pyruvate - lactate - glycerol - certain AA (alanine, aspartate)

Question 85

When is the Cori cycle active?

Answer 85

after exercise

Question 86

Cori cycle

Answer 86

muscles get glucose from stored glycogen

Question 87

What is glucose converted to in the Cori cycle?

Answer 87

lactic acid

Question 88

What happens to the lactic acid in the Cori

Answer 88

redirected to liver for gluconeogensis

Question 89

Where is the glucose released in the Cori cycle?

Answer 89

into blood

Question 90

Where is glucose taken up in the Cori cycle?

Answer 90

- muscle | - used for energy and stored as glycogen