Metabolism Part II Flashcards

(81 cards)

1
Q

What are the 4 fates of pyruvate?

A
  1. Acetyl CoA
  2. Oxaloacetate
  3. Alanine
  4. Lactate
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2
Q

What enzyme converts pyruvate to Acetyl CoA

A

Pyruvate Dehydrogenase

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3
Q

What factors regulate pyruvate dehydrogenase?

A
TLC for Nobody
Thiamine pyrophosphate (TPP) - active B1
Lipoic acid
Coenzyme A - B5
FAD - B2
NAD+ - B3
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4
Q

What B vitamins are needed to make Acetyl CoA?

A

B1, B2, B3, B5

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5
Q

What factor does arsenic inhibit

A

Lipoic acid - cofactor for PDH

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6
Q

Arsenic poisoning features

A

Garlic breath, vomiting, rice water stool

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7
Q

What happens in PDH deficiency and what clinical features result

A

Back up of pyruvate that gets converted to other things: Lactate, Alanine.
Lactic acidosis
Neurologic defects

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8
Q

What is treatment of PDH deficiency

A

Increase intake of ketogenic nutrients (high fat, high lysine and leucine) - so can make Acetyl CoA from something else. Ketone bodies can be used for energy instead of glucose.

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9
Q

How is PDH deficiency acquired?

A

Arsenic exposure, B vitamin deficiency (especially B1)

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10
Q

What does TCA enzyme citrate synthase do

A

Makes citrate from Acetyl CoA and oxaloacetate

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11
Q

What does isocitrate dehydrogenase do

A

Converts isocitrate into alpha ketoglutarate

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12
Q

What is the rate limiting enzyme in the TCA cycle

A

Isocitrate dehydrogenase

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13
Q

What does alpha ketoglutarate dehydrogenase do

A

Converts alpha ketoglutarate to succinyl-CoA

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14
Q

Why is alpha ketoglutarate dehydrogenase so regulated

A

Requires same cofactors as PDH complex: TPP, lipoic acid, coenzyme A, NAD, FAD+

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15
Q

How many moles of ATP are produced per NADH in ETC?

A

2.5

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16
Q

How many moles of ATP are produced per FADH2 in ETC?

A

1.5

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17
Q

What effect does Amytal (a barbiturate) have on ETC?

A

Blocks Complex I

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18
Q

What effect does Rotenone have on ETC?

A

Blocks Complex I

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19
Q

What effect does MPP have on ETC?

A

Blocks Complex I

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20
Q

What effect does Antimycin A have on ETC?

A

Blocks Complex III

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21
Q

What effect does CN have on ETC?

A

Blocks Complex IV

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22
Q

What can inhibit complex IV of the ETC?

A

CO, N3-, CN, H2S (hydrogen sulfide)

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23
Q

What can inhibit the ATPase of ETC?

A

Oligomycin A (macrolide antibiotic)

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24
Q

What affect do uncoupling agents have on inner mitochondrial membrane

A

Make it more permeable to H+ ions - generate more heat in the bottom

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25
What is thermogenin
An uncoupling agent for heat in hibernation - found in brown fat
26
What are some uncoupling agents?
Aspirin Thermogenin 2,4-Dinitrophenol
27
What enzymes convert lactate and pyruvate?
Lactate dehydrogenase
28
What happens to lactate in the liver
Lactate (from anaerobic glycolysis in muscles, RBCs) gets converted back to pyruvate via LDH. Pyruvate can be used for gluconeogenesis.
29
How are the alanine cycle and cori cycle similar?
Muscles make something that goes to the liver to be made into glucose
30
Describe steps of alanine cycle
Pyruvate gets converted to alanine in muscle It goes in serum to liver, where it is uptaken, converted back to pyruvate -> glucose
31
Why are alanine and glutamine found in such high concentrations in the blood?
Ala and glutamine are two major carriers of nitrogen from tissues. Liver uses glutamine to make urea.
32
What is generally involved in transamination?
transfer of amino group of an amino acid to alpha ketoglutarate to form glutamate. the remaining deaminated amino acid is a ketoacid (eg pyruvate) that is used in energy metabolism
33
What enzyme catalyzes transamination?
Aminotransferases
34
How are aminotransferases named?
By donor of the amino group (alanine aminotransferase converts alanine to pyruvate and forms glutamate)
35
In addition to substrates, what is required by all aminotransferases?
Pyridoxal phosphate (a derivative of B6)
36
What are the substrates and products of alanine aminotransferase?
Alanine+aKG -> Glutamate + Pyruvate
37
What are the substrates and products of aspartate aminotransferase?
Aspartate+aKG -> Glutamate + oxaloacetate
38
What are the two main carriers of nitrogen in the blood?
Alanine + Glutamine
39
What is NADPH needed for? 4 reasons
Make FA's and Cholesterol Make O2 free radicals Inside RBCs to protect from O2 free radicals Cytochrome p450
40
Most important enzyme of the HMP shunt
G6PD
41
What does G6PD do
Converts G-6-P to Ribulose 5-P and get 2 NADPH
42
What is needed to create oxygen free radicals
Oxygen, NADPH, and NADPH oxidase
43
What converts free radical oxygen to hydrogen peroxide
Superoxide dismutase
44
What does myeloperoxidase do
Converts hydrogen peroxide to hypochlorus acid HOCl
45
What disease results from deficiency of NADPH oxidase
Chronic granulomatous disease - susceptible to catalase positive organisms because neutralize environmental hydrogen peroxide to water
46
What does glutathione peroxidase do
Converts hydrogen peroxide into water, by letting H2O2 react with reduced glutathione (GSH)
47
What is reduced glutathione
An antioxidant required to neutralize H2O2 into water
48
How is glutathione disulfide converted back to reduced glutathione?
Glutathione reductase
49
What does glutathione reductase use as an electron donor
NADPH (to reduce glutathione)
50
What keeps the steady supply of NADPH around in order to continue to reduce glutathione for antioxidation?
G6PD
51
What are some drugs that "oxidize" red blood cells and so are problematic in G6PD deficiency (-> hemolytic anemia)
``` Anti malarial drugs primaquine and chloroquine Nitrofurantoin Dapsone Sulfonamide Isoniazid Naphthalene (moth balls) Fava beans Ibuprofen High dose ASA ```
52
What enzyme is deficient in essential fructosuria
Fructokinase
53
What enzyme is deficient in fructose intolerance
Aldolase B
54
Why is essential fructosuria benign
Fructose doesn't get trapped in cells - have it spilling out into blood and urine
55
What is pathophysiology of fructose intolerance/ aldolase B deficiency?
Cannot correct fasting hypoglycemia - accumulation of fructose 1-P in cells causes decreased available phosphate(using it up), inhibits glycogenolysis and gluconeogenesis.
56
What are clinical symptoms of fructose intolerance
Hypoglycemia Vomiting - after fructose or sucrose Hepatomegaly, jaundice
57
What enzyme is deficient in galactokinase deficiency
Galactokinase - can't convert galactose to galactose-1-p
58
What is pathophysiology and clinical features of galactokinase deficiency
Galactose converts to galactitol which accumulates in the blood and can appear in blood and urine, cause infantile cataracts
59
What enzyme is deficient in classic galactosemia
Absence of galactose-1-phosphate uridyltransferase
60
Pathophysiology of classic galactosemia
Accumulation of toxic substances galactose-1P and galactitol
61
Clinical features of galactosemia
Hepatomegaly, jaundice, FTT, infantile cataracts, intellectual disability
62
What is the treatment for galactosemia
Exclude galactose and lactose from diet
63
Rate limiting step of pentose phosphate pathway
G6PD
64
Which tissues use pentose phosphate pathway
RBCs, Liver, Adrenal cortex, Mammary glands (during lactation)
65
What disease is caused by deficiency of galactokinase
Galactokinase deficiency
66
What disease is caused by deficiency of aldolase B deficiency
Fructose intolerance
67
What disease is caused by deficiency of galactose-1-phosphate uridyltransferase
Classic galactosemia
68
What disease is caused by deficiency of fructokinase
Essential fructosuria
69
What is the primary energy source in a patient who has not eaten in 2 days
Fatty acids
70
Rate limiting enzyme in ketone body synthesis
HMG CoA synthase
71
Why do people get hypoglycemic after drinking alcohol?
NADH produced which shunts pyruvate toward production of lactate, shunts oxaloacetate toward production of malate, so pyruvate and oxaloacetate are not available to undergo gluconeogenesis
72
Hallmark features of Kwashiorkor
``` FLAME Fatty Liver Anemia Malnutrition (protein) Edema Skin lesion, skin and hair depigmentation ```
73
When does gluconeogenesis start in the post-absorptive period?
Starts 4-6 hours after last meal | Full active when glycogen stores are depleted
74
When are glycogen stores depleted
10-18 hours
75
What are the two main ketone bodies made in the liver
Acetoacetate and Beta-hydroxybutyrate are made from fatty acids and amino acids using NADH
76
What causes fruity breath smell in ketosis
Acetoacetate spontaneously becomes acetone
77
What does urine test for ketones test for
Acetoacetate only
78
When do you start making ketones?
When you have so many fatty acids and so much acetyl coA that TCA cycle can't handle it all; Oxaloacetate depleted for gluconeogenesis
79
What metabolic scenario favors synthesis of ketone bodies
When production of acetyl CoA from beta oxidation of FA's exceeds oxidative capacity of the TCA cycle
80
What is marasmus
Total energy malnutrition (deficient in everything)
81
What is refeeding syndrome
Drop in serum Mg, Phosphate, and K+, can lead to arrhythmias and neurologic problems Overall ATP depletion - phosphorylating glucose in cells depletes it.