Metabolic Pathways Flashcards

1
Q

Site of citric acid cycle

A

Mitochondrial matrix

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2
Q

Major roles of CAC

A
  1. Generate ATP by generating reduced carriers for oxidative phosphorylation (NADH and FADH2) and a GTP
  2. Generate metabolic precursors
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3
Q

Substrate of CAC

A

Acetyl-CoA

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4
Q

Where can substrate for CAC come from?

A

From pyruvate (glycolysis), B-oxidation of fatty acids, or ketogenic amino acids

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5
Q

Metabolic product of CAC

A

Oxaloacetate

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6
Q

Key/entry enzyme of CAC

A

Citrate synthase (acetyl-CoA + OAA –> citrate)

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7
Q

What are the other important products of the CAC?

A

3 NADH (formation of α-ketoglutarate, succinyl CoA, and OAA), 1 FADH2 (formation of fumarate), 1 GTP (formation of succinate), 2 CO2 (α-KG and succinyl CoA)

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8
Q

Site of PDH complex

A

Mitochondrial matrix

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9
Q

Major role of PDH complex

A

Links glycolysis to CAC

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10
Q

Substrate for PDH complex

A

Pyruvate

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11
Q

Where does the substrate for PDH complex come from?

A

Mainly glycolysis, also alanine and lactate

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12
Q

Metabolic product of PDH complex

A

Acetyl-CoA

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13
Q

Key/entry enzyme for PDH complex

A

Pyruvate dehydrogenase (PDH) complex

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14
Q

What are the other important products of PDH complex?

A

1 NADH, 1 CO2 (by decarboxylation)

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15
Q

4 B-vitamins involved in PDH complex reaction

A
  1. Riboflavin (B2, FAD)
  2. Niacin (B3, NAD)
  3. Thiamin (B1, TPP)
  4. Pantothenic acid (B5, CoA)
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16
Q

What does deficiency of niacin lead to?

A

Pellagra (4 D’s)

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17
Q

What does deficiency of thiamin lead to?

A

Beri-beri (alcoholics, elderly, and low-income)

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18
Q

Lactic acidosis and PDH complex

A

Decreased complex activity leads to lactate generation

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19
Q

Site of glycolysis

A

Cytosol

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20
Q

Major role of glycolysis

A

Generate ATP (and pyruvate)

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21
Q

Substrate of glycolysis

A

Glucose (and other hexoses)

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22
Q

Metabolic product of glycolysis

A

Pyruvate (–> lactate in anaerobic conditions or RBCs)

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23
Q

Key/entry enzymes of glycolysis

A
  1. Hexokinase (entry)
  2. Phosphofructokinase (key regulator)
  3. Pyruvate kinase (forms ATP)
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24
Q

What does deficiency of pyruvate kinase in glycolysis lead to?

A

Hereditary nonspherocytic hemolytic anemia

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25
What are the other important products of glycolysis?
2 NADH per glucose, 2 net ATP per glucose
26
What happens after glycolysis in aerobic conditions?
Pyruvate --> acetyl-CoA --> CAC
27
What happens after glycolysis in anaerobic conditions?
Pyruvate --> lactate to regenerate NAD+
28
Site of gluconeogenesis
Cytosol (mainly -- also mitochondria)
29
Major role of gluconeogenesis
Generation of blood glucose
30
Substrates of gluconeogenesis
1. Lactate (via pyruvate) 2. Glycerol (from TAG breakdown) 3. Gluconeogenic amino acids, especially glutamine and alanine - -Also ODD chain-length fatty acids (NOT acetyl-CoA)
31
Metabolic product of gluconeogenesis
Glucose
32
Key/entry enzymes in gluconeogenesis
1. Pyruvate carboxylase (pyruvate --> oxaloacetate) 2. PEP carboxykinase (OAA --> phosphoenolpyruvate) - --F1,6-bisphosphatase (F1,6BP --> F6P)*** 3. G-6-phosphatase (G6P --> glucose)
33
Which organ does gluconeogenesis mainly occur in?
Liver (kidney in starvation)
34
Site of glycogenesis
Cytosol
35
Major role of glycogenesis
Storage of glucose or G6P as glycogen
36
Substrate of glycogenesis
G6P (from glycolysis)
37
Metabolic product of glycogenesis
Glycogen
38
Key/entry enzyme of glycogenesis
Glycogen synthase
39
How can glycogenesis be inhibited?
By phosphorylation of enzymes in response to hormones
40
Site of glycogenolysis
Cytosol
41
Major roles of glycogenolysis
1. Supply glucose for ATP generation for contraction (muscle) 2. Maintain blood glucose (liver)
42
Substrate for glycogenolysis
Glycogen
43
Metabolic product of glycogenolysis
G6P or glucose in liver
44
Key/entry enzyme of glycogenolysis
Glycogen phosphorylase (forms G1P with Pi)
45
Site of pentose phosphate pathway
Cytosol
46
Major roles of PPP
1. Form NADPH for biosynthesis | 2. Form ribose-5-P for nucleotide synthesis
47
Substrate of PPP
G6P (from glycolysis)
48
Metabolic products of PPP
Ribose-5-P, fructose-6-P and glyceraldehyde-3-P (glycolysis), 2 NADPH per glucose
49
What are the other important products of PPP?
1 CO2 per glucose
50
Key/entry enzyme of PPP
G6PD (forms NADPH)
51
What dose deficiency of G6PD lead to?
Hemolytic anemia and Heinz bodies in RBCs
52
Site of fatty acid B-oxidation
Mitochondrial matrix
53
Major roles of fatty acid B-oxidation
1. Generate acetyl-CoA for ATP production via CAC and oxidative phosphorylation 2. Generate FADH2 and NADH for ATP generation via oxidative phosphorylation
54
Substrate for fatty acid B-oxidation
Fatty acyl-CoA
55
Metabolic product of fatty acid B-oxidation
Acetyl-CoA
56
What are the other important products of fatty acid B-oxidation?
FADH2 (2 ATP via ox-phos), NADH (3 ATP)
57
How does uptake of long chain fatty acids occur in mitochondria?
Facilitation by carnitine
58
How are fatty acids carried from adipocytes?
By albumin in serum
59
What types of tissues/organs prefer fatty acids?
Red muscle tissue; anything with abundant mitochondria
60
Where does B-oxidation of very long chain fatty acids occur initially?
Peroxisomes
61
What states promote a higher rate of fatty acid B-oxidation?
Fasting/starvation, uncontrolled diabetes, and low carbohydrate diets
62
Site of fatty acid biosynthesis
Cytosol
63
Major role of fatty acid biosynthesis
Make fatty acids, mainly for storage
64
Substrate for fatty acid biosynthesis
Acetyl-CoA (carboxylated to malonyl-CoA)
65
Metabolic product of fatty acid biosynthesis
Saturated fatty acids, mainly C16 palmitate
66
What are other important products of fatty acid biosynthesis?
NADP+ from NADPH (2 NADPH required for every 2C) and CO2 from malonyl-CoA
67
Key/entry enzyme of fatty acid biosynthesis
1. Acetyl-CoA carboxylase (acetyl-CoA + CO2 --> malonyl-CoA) -- REQUIRES ATP 2. Fatty acid synthase complex
68
What needs to occur with the substrate before fatty acid biosynthesis can occur?
Acetyl-CoA groups are formed in mitochondria -- need to be transported to cytosol as citrate and cleaved to acetyl-CoA and OAA
69
What provides the attachment site in synthase complex of fatty acid biosynthesis?
Phosphopantotheine with -SH group, a derivative of pantothenic acid (vitamin B5)
70
Site of ketogenesis
Mitochondria
71
Major role of ketogenesis
Form water-soluble derivatives of fatty acids (ketone bodies) which can serve as important metabolic fuels for many tissues, especially the brain
72
Substrate for ketogenesis
Acetyl-CoA
73
Metabolic products of ketogenesis
3 ketone bodies: 1. Acetoacetate 2. B-hydroxybutyrate 3. Acetone
74
Why would ketogenesis occur?
Spares utilization of glucose and endogenous protein
75
What states promote higher rate of ketogenesis?
Starvation, poorly controlled diabetes (especially type I), and low carbohydrate diets
76
What is the reaction catalyzed by pyruvate carboxylase?
Pyruvate --> OAA
77
What enzymes use biotin?
- -Pyruvate carboxylase | - -Acetyl-CoA carboxylase
78
What processes occur in the well-fed state?
CAC, glycolysis, PDH complex, glycogenenesis, fatty acid biosynthesis
79
What processes occur in fasting state?
Gluconeogenesis, glycogenolysis, fatty acid B-oxidation, ketogenesis