Lactate Metabolism Flashcards

1
Q

What is the only compound lactate can be converted to while actively exercising?

A

pyruvate

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2
Q

which enzyme is responsible for the conversion of lactate to pyruvate and vice versa?

A

Lactate Dehydrogenase (LDH)

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3
Q

Why can’t lactate to pyruvate conversion occur while muscle is active?

A

lack of NAD+

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4
Q

Which type of compounds facilitates Lactate Efflux?

A

Monocarboxylate Transporters (MCT)

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5
Q

Where are MCTs located?

A

Sarcolemma and T-tubule membrane (mitochondrial membrane)

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6
Q

Aside from lactate what else can MCTs transport? give an example

A

other monocarboxylates i.e. pyruvate

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7
Q

Along with lactate what other substances are carried across the membrane by MCTs? Why is this important?

A

H+ ions
helps manage pH, lowers cytosolic H+

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8
Q

Functional activity of MCT1,

A

dependent on a proton gradient, unidirectional transport across plasma membrane

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9
Q

Examples of monocarboxylates transported by MCT1

A

lactate,pyruvate,acetoacetic acid

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10
Q

Pyruvate Dehydrogenase

A

Irreversible decarboxylation of pyruvate to acetyl-CoA

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11
Q

Where is MCT 4 primarily found?

A

Skeletal Muscle
Skin
Vas Deferens

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12
Q

Where is lactate primarily utilized?

A

Heart
Liver
Brain and Kidney to a lesser extent

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13
Q

In which type of skeletal muscle is lactate primarily formed?

A

type IIb

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14
Q

In which type of skeletal muscle is lactate primarily utilized?

A

Type I

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15
Q

In type 1 muscle fibers, what is lactate converted to?

A

Pyruvate

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16
Q

In the heart what is lactate converted to?

A

Pyruvate

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17
Q

Shuttle system responsible for bringing NADH into mitochondira

A

Malate-Aspartate

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18
Q

This type of muscle has few mitochondria

A

Fast Glycolytic Muscle (type IIx)

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19
Q

What is the Cori cycle?

A

lactate (or pyruvate) formed in muscle can circulate to the liver where it can be synthesized to glucose. Glucose formed can then enter circulation and return to muscle

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20
Q

Mitochondrial LDH

A

Lactate dehydrogenase specific to mitochondria

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21
Q

Gluconeogenesis

A

Requires ATP; the synthesis of glucose from compounds that are not carbohydrates (pyruvate, lactate, glycerol, most aa’s)

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22
Q

Why is the amino acid pathway of gluconeogenesis unique?

A

Nitrogen group must first be removed

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23
Q

First step in gluconeogenesis from lactate

A

Conversion of lactate to pyruvate

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24
Q

Glucose synthesis from pyruvate (or lactate) can best be described as what?

A

The reversal of glycolysis

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25
How many reversible reactions are there in glycolysis?
7
26
What are the irreversible glycolytic reactions?
Hexokinase Phosphofructokinase Pyruvate Kinase
27
Why is the PFK reaction not possible in reverse?
The first phosphate group in fructose 1,6 biphosphate must be removed from the first carbon, PFK can't do this
28
Why is the Hexokinase reaction not possible in reverse?
Phosphoryl group needs to be removed from glucose 6 phosphate to form glucose, hexokinase can't do this.
29
Why is it essential to form malate for gluconeogenesis to occur?
Malate can pass through the mitochondrial inner membrane
30
Where does gluconeogenesis occur?
Primarily in the cytosol, however pyruvate must be converted to oxaloacetate in mitochondria.
31
Glycolysis Specific enzymes
Hexokinase Phosphofructo kinase pyruvate kinase
32
Gluconeogenesis specific enzymes
Glucose 6 Phosphatase Fructose 1,6 Biphosphatase Pyruvate carboxylase phosphoenolpyruvate carboxykinase
33
Pyruvate Carboxylase
Irreversible Pyruvate +HCO3 + ATP > oxaloacetate + ADP + Pi + H+
34
Mitochondrial Malate Dehydrogenase
IN MITOCHONDRIA Reversible Oxaloacetate + NADH + H+ <> L-malate + NAD+
35
Cytosolic Malate Dehydrogenase
IN CYTOSOL Irreversible Malte + NAD+ > Oxaloacetate + NADH +H +
36
Phosphoenolpyruvate Carboxykinase
Reversible Oxaloacetate + GTP <> Phosphoenolpyruvate + CO2 + GDP
37
What does low levels of Fructose 1,6 Biphosphate Indicate?
Low levels of glucose
38
Fructose 1,6 Biphosphatase
2nd Bypass Irreversible hydrolysis of Carbon 1 phosphate Fructose 1,6 Biphosphate + H20 > Fructose 6 phosphate + Pi
39
Phosphohexose Isomerase
Irreversible Fructose 6 Phosphate > Glucose 6 Phosphate
40
Glucose 6 Phosphatase
3 rd bypass dephosphorylation of G6P G6P + H2O > Glucose + Pi
41
Main organs in which gluconeogenesis occurs?
Liver and Kidneys
42
Why can't gluconeogenesis occur in muscle tissue?
Muscle tissue lacks Glucose 6 Phosphatase
43
What can lactate and pyruvate be converted to in muscle?
Glycogen
44
What are the potential fates of Glucose 6 phosphate?
Fructose 6 phosphate Glycogen 6 phosphogluconate
45
What is liver glycogen broken down into?
Glucose 6 Phosphate
46
Where do branching enzymes act on glycogen chains?
every 4th glycosyl
47
What is glycogenesis
Synthesis of glycogen the storage form of glucose
48
Where does glycogenesis primarily occur?
Liver (hepatocytes) Muscle cells
49
What is the fate of liver glycogen?
conversion to blood glucose distributed to other tissues
50
What is the fate of muscle glycogen?
broken down via glycolysis to provide ATP for muscle contraction
51
What is the glycogen core made of?
Glycogenin
52
what is the role of the glycogen core?
primer to which first glucose residue is attached catalyst for synthesis of developing glycogen molecule
53
What other metabolic process shares the same first step as glycogenesis?
Glycolysis
54
Glycogen Synthase
Biosynthetic (requires energy) adds additional glycosyl units to glycogen branch
55
With which molecule does glycogenesis officially start?
Glucose 6 Phosphate
56
Why can erythrocytes only form lactate?
no mitochondria
57
Phosphoglucomutase (glycogenesis)
Reversible unique form of phosphoglucomutase Glucose 6 phosphate <> Glucose 1 phosphate
58
UDP Glucose Pyrophosphorylase
RATE LIMITING STEP in glycogenesis Irreversible Glucose 1 Phosphate + UTP > UDP glucose + PPi
59
What happens if Inorganic Pyrophosphate is allowed to accumulate?
the reaction becomes unfavorable
60
Inorganic Pyrophosphatase
Responsible for managing PPi formed during production of UDP Glucose - rapidly hydrolyzes PPi
61
Glycogen Synthase
Forms glycogen from UDP glucose, ONLY FORMS CHAINS extends chains
62
How is glycogenin formed?
protein synthesis
63
Branching Enzyme
Glycosyl (4>6) Tranferase or Amylo (1>4 to (1>6) transglycosylase Branches glycogen chain at every 4th glucosyl detaches segments of existing chain and transports to the interior.
64
What is glycogenolysis
the degradation of glycogen
65
Which enzyme catalyzes the breakdown of glycogen?
Glycogen Phosphorylase (phosphorylase) Glycogen (n units) + Pi > Glycogen (n-1 units) + glucose 1 phosphate
66
Enzyme responsible for breaking down glycogen bonds in chains with 4 or fewer units from branch point?
Debranching Enzyme
67
Reactions catalyzed by debranching enzyme
1. Transport of three (of 4) glucosyl units of a branch to the other end 2. Removal of the final remaining unit by hydrolysis of glycosidic linkage (alpha1 >6)
68
Phosphoglucomutase (glycogenolysis)
Conversion of glucose 1 phosphate to glucose 6 phosphate
69
How many ATP equivalents are produced from the breakdown of G6P from glycogen? Why is this important?
3 - bypassing hexokinase reaction conserves ATP
70
What is the Pentose Phosphate Pathway
Conversion of 6 C Hexose to 5 C Pentose sugar Glucose 6 phosphate > 6 phosphogluconate > Ribose 5 phosphate
71
Where is activity of the pentose phosphate pathway highest? where is it lowest?
Highest in adipose tissue lowest in skeletal muscle
72
Which molecule regulates the first step of the pentose phosphate pathway?
NADPH
73
Enzyme inhibited by NADPH/NADP
Glucose 6 phosphate dehydrogenase
74
What does high levels of NADPH/NADP and NAD/NADH indicate
That biosynthetic and glycolytic reactions can occur at the same time
75
NADPH is involved in the biosynthesis of which molecules?
Fatty acids Cholesterol (steroids)
76
Ribose 5 phosphate is involved in the synthesis of which molecules?
nucleotides (ATP, CoA, NAD, FAD, NADP, RNA, DNA)