Metabolism I Flashcards

1
Q

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

A
  • glucose
  • FA
  • AA
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2
Q

Sources of ATP

A
  • Adenylate kinase
  • Creatine phosphokinase/phosphocreatine (CPK)
  • Anaerobic metabolism
  • Aerobic metabolism
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3
Q

Glycolysis

A

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

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4
Q

Where does glycolysis occur?

A

Cytoplasm

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5
Q

How many steps are there in glycolysis?

A

10 steps

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6
Q

Major points in glycolysis

A

glucose –> C6P –> pyruvate –> acetyl CoA

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7
Q

Three enzymes of glycolysis

A
  • hexokinase (HK)
  • PFK
  • PK
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8
Q

Where does pyruvate go after glycolysis

A
  • Lactate (PDH pathway)

- acetyl CoA –> TCA cycle (PDH pathway)

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9
Q

How many stages is glycolysis broken into?

A

3

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10
Q

Where does the formation of acetyl CoA occur?

A

mitochondria

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11
Q

What enzyme is responsible for pyruvate conversion to acetyl CoA?

A

Pyruvate dehydrogenase complex

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12
Q

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

A

2 ATP

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13
Q

Where does the Kreb’s cycle occur?

A

Mitochondria

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14
Q

What does the Kreb’s cycle depend on?

A

availability of substrates and cofactors

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15
Q

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

A

36 ATP

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16
Q

What is the net energy of ATP from glycolysis?

A

2 ATP

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17
Q

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

A

32 ATP

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18
Q

What regulates glycolysis?

A
  • Hexokinase

- Glucokinase

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19
Q

How many isoforms of hexokinase are present?

A

4

I, II, III and IV

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20
Q

What is HK IV called?

A

glucokinase

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21
Q

Where are HK I - III found?

A

in most tissues

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22
Q

HK I - III Km

A

Low Km for glucose relative to its concentration in blood

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23
Q

What is HK I - III inhibited by?

A

Strongly inhibited by G6P

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24
Q

Where is HK IV found?

A

liver and pancreas

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25
HK IV and Km
high KM for glucose
26
HK IV inhibition
less sensitive to inhibition by G6P
27
What is glucokinase regulated by?
- F6P | - fructose
28
GK inhibitory protein
- GK-RP | - sequesters GK as an inactive complex in nucleus
29
Where is GK-RP found?
nucleus of liver cells
30
What promotes the binding of GK to GK-RP?
F6P
31
What inhibits GK?
F6P
32
How is F6P inhibition of GK overcome?
by large increase in glucose concentration
33
Fructose and GK
- fruits - vegetables - high fructose corn syrup
34
What does fructose get converted to?
F1P
35
What activates GK?
F1P
36
Role of F1P
- promotes hepatic glucose utilization | - partly responsible for adverse effects of fructose consumption (lipogenesis, hypertriglyceridemia etc)
37
GK as an enzyme
inducible
38
What stimulates GK transcription?
Insulin
39
What can a mutation in GK lead to?
a form of MODY
40
What does PFK1 catalyze?
the first committed step in glycolysis
41
What are the negative effectors of PFK1?
ATP Low pH Citrate
42
What are the positive effectors of PFK1?
AMP (cAMP) | F2,6BP
43
What inhibits PFK1?
ATP (negative allosteric effector)
44
What promotes PFK1 activity?
AMP (positive allosteric effector)
45
What does F1,6 BP'ase catalyze?
an irreversible reaction opposite to that catalyzed by PFK1
46
What doe PFK1 and F1-6BP'ase together catalyze?
futile cycle
47
What inhibits F1,6 P'ase?
AMP
48
What does the inhibition of F1,6 P'ase lead to?
- increased F1, 6BP | - glycolytic flux
49
What is PFK1 regulated by?
- intracellular pH - citrate - H + ions
50
What is PFK1 not regulated by?
Lactic acid (the end product of glycolysis)
51
What do some tissues prefer as fuels instead of glucose?
FA and ketone bodies
52
Why do some tissues prefer FA and ketone bodies over glucose?
to spare glucose for use by organs which specifically require glucose for energy (brain)
53
What does citrate inhibit?
PFK1 | - thus glucose utilization
54
Where does citrate accumulate?
in cytosol
55
What inhibits glycolysis?
Glycogen | Epinephrine
56
What is a positive allosteric effector of PFK1?
F2,6P
57
What happens if there if no F2, 6P?
glycolysis cannot occur in liver
58
What triggers adenylate cyclase through cAMP?
binding of glucagon to its receptor triggers
59
What does adenylate cyclase through cAMP cause?
decrease in F2, 6P
60
What does a decrease in F2, 6P lead to?
- reduces PFK1 - activates F1, 6BPase - inhibit glycolysis
61
F1, 6P and glycolysis
intermediate via PFK1
62
F2, 6P and glycolysis
side product via PFK2
63
What does F2,6BPase oppose?
PFK2 bi-functional enzyme - same protein
64
What inactivates kinase?
Phosphorylation
65
What activates phosphatase activity?
phosphorylation
66
What activates kinase?
dephosphorylation
67
What inactivates phosphatase activity?
dephosphorylation
68
What regulates glycolysis?
- PK
69
What inhibits PK?
physiological concentration of ATP
70
What activates PK?
F1, 6BP
71
Is PK active or inactive in the phosphorylated state?
inactive
72
Is PK active or inactive in the dephosphorylated state?
active
73
What causes a change in activity of PK?
covalent modification by PKA
74
What is PK induced by?
- high carbohydrate intake - high insulin levels - in liver
75
Glycogen synthase
- converts glucose to glycogen - insulin promotes glycogen synthesis - fed state
76
Glycogen phosphorylase
- breakdown glycogen to glucose - glucagon promotes glycogen breakdown - fasted state
77
When is glycogen synthase active?
fed state
78
When is glycogen phosphorylase active?
fasted state
79
Gluconeogenesis
formation of new sugar
80
When is gluconeogeneis activated?
- fasting condition | - during exercise
81
What promotes gluconeogenesis?
Glucagon to protect against hypoglycemia
82
What does gluconeogenesis provide glucose for?
brain muscles erythrocytes
83
Where does gluconeogenesis take place?
- mainly in liver | - small extent renal cortex
84
What are the precursors for gluconeogensis?
- pyruvate - lactate - glycerol - certain AA (alanine, aspartate)
85
When is the Cori cycle active?
after exercise
86
Cori cycle
muscles get glucose from stored glycogen
87
What is glucose converted to in the Cori cycle?
lactic acid
88
What happens to the lactic acid in the Cori
redirected to liver for gluconeogensis
89
Where is the glucose released in the Cori cycle?
into blood
90
Where is glucose taken up in the Cori cycle?
- muscle | - used for energy and stored as glycogen