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
Q

How many reversible reactions are there in glycolysis?

A

7

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26
Q

What are the irreversible glycolytic reactions?

A

Hexokinase
Phosphofructokinase
Pyruvate Kinase

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27
Q

Why is the PFK reaction not possible in reverse?

A

The first phosphate group in fructose 1,6 biphosphate must be removed from the first carbon, PFK can’t do this

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28
Q

Why is the Hexokinase reaction not possible in reverse?

A

Phosphoryl group needs to be removed from glucose 6 phosphate to form glucose, hexokinase can’t do this.

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29
Q

Why is it essential to form malate for gluconeogenesis to occur?

A

Malate can pass through the mitochondrial inner membrane

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30
Q

Where does gluconeogenesis occur?

A

Primarily in the cytosol, however pyruvate must be converted to oxaloacetate in mitochondria.

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31
Q

Glycolysis Specific enzymes

A

Hexokinase
Phosphofructo kinase
pyruvate kinase

32
Q

Gluconeogenesis specific enzymes

A

Glucose 6 Phosphatase
Fructose 1,6 Biphosphatase
Pyruvate carboxylase
phosphoenolpyruvate carboxykinase

33
Q

Pyruvate Carboxylase

A

Irreversible
Pyruvate +HCO3 + ATP > oxaloacetate + ADP + Pi + H+

34
Q

Mitochondrial Malate Dehydrogenase

A

IN MITOCHONDRIA
Reversible
Oxaloacetate + NADH + H+ <> L-malate + NAD+

35
Q

Cytosolic Malate Dehydrogenase

A

IN CYTOSOL
Irreversible
Malte + NAD+ > Oxaloacetate + NADH +H +

36
Q

Phosphoenolpyruvate Carboxykinase

A

Reversible
Oxaloacetate + GTP <> Phosphoenolpyruvate + CO2 + GDP

37
Q

What does low levels of Fructose 1,6 Biphosphate Indicate?

A

Low levels of glucose

38
Q

Fructose 1,6 Biphosphatase

A

2nd Bypass
Irreversible hydrolysis of Carbon 1 phosphate
Fructose 1,6 Biphosphate + H20 > Fructose 6 phosphate + Pi

39
Q

Phosphohexose Isomerase

A

Irreversible
Fructose 6 Phosphate > Glucose 6 Phosphate

40
Q

Glucose 6 Phosphatase

A

3 rd bypass
dephosphorylation of G6P
G6P + H2O > Glucose + Pi

41
Q

Main organs in which gluconeogenesis occurs?

A

Liver and Kidneys

42
Q

Why can’t gluconeogenesis occur in muscle tissue?

A

Muscle tissue lacks Glucose 6 Phosphatase

43
Q

What can lactate and pyruvate be converted to in muscle?

A

Glycogen

44
Q

What are the potential fates of Glucose 6 phosphate?

A

Fructose 6 phosphate
Glycogen
6 phosphogluconate

45
Q

What is liver glycogen broken down into?

A

Glucose 6 Phosphate

46
Q

Where do branching enzymes act on glycogen chains?

A

every 4th glycosyl

47
Q

What is glycogenesis

A

Synthesis of glycogen the storage form of glucose

48
Q

Where does glycogenesis primarily occur?

A

Liver (hepatocytes)
Muscle cells

49
Q

What is the fate of liver glycogen?

A

conversion to blood glucose distributed to other tissues

50
Q

What is the fate of muscle glycogen?

A

broken down via glycolysis to provide ATP for muscle contraction

51
Q

What is the glycogen core made of?

A

Glycogenin

52
Q

what is the role of the glycogen core?

A

primer to which first glucose residue is attached
catalyst for synthesis of developing glycogen molecule

53
Q

What other metabolic process shares the same first step as glycogenesis?

A

Glycolysis

54
Q

Glycogen Synthase

A

Biosynthetic (requires energy)
adds additional glycosyl units to glycogen branch

55
Q

With which molecule does glycogenesis officially start?

A

Glucose 6 Phosphate

56
Q

Why can erythrocytes only form lactate?

A

no mitochondria

57
Q

Phosphoglucomutase (glycogenesis)

A

Reversible
unique form of phosphoglucomutase
Glucose 6 phosphate <> Glucose 1 phosphate

58
Q

UDP Glucose Pyrophosphorylase

A

RATE LIMITING STEP in glycogenesis
Irreversible
Glucose 1 Phosphate + UTP > UDP glucose + PPi

59
Q

What happens if Inorganic Pyrophosphate is allowed to accumulate?

A

the reaction becomes unfavorable

60
Q

Inorganic Pyrophosphatase

A

Responsible for managing PPi formed during production of UDP Glucose
- rapidly hydrolyzes PPi

61
Q

Glycogen Synthase

A

Forms glycogen from UDP glucose,
ONLY FORMS CHAINS
extends chains

62
Q

How is glycogenin formed?

A

protein synthesis

63
Q

Branching Enzyme

A

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
Q

What is glycogenolysis

A

the degradation of glycogen

65
Q

Which enzyme catalyzes the breakdown of glycogen?

A

Glycogen Phosphorylase (phosphorylase)

Glycogen (n units) + Pi > Glycogen (n-1 units) + glucose 1 phosphate

66
Q

Enzyme responsible for breaking down glycogen bonds in chains with 4 or fewer units from branch point?

A

Debranching Enzyme

67
Q

Reactions catalyzed by debranching enzyme

A
  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
Q

Phosphoglucomutase (glycogenolysis)

A

Conversion of glucose 1 phosphate to glucose 6 phosphate

69
Q

How many ATP equivalents are produced from the breakdown of G6P from glycogen? Why is this important?

A

3 - bypassing hexokinase reaction conserves ATP

70
Q

What is the Pentose Phosphate Pathway

A

Conversion of 6 C Hexose to 5 C Pentose sugar

Glucose 6 phosphate > 6 phosphogluconate > Ribose 5 phosphate

71
Q

Where is activity of the pentose phosphate pathway highest? where is it lowest?

A

Highest in adipose tissue
lowest in skeletal muscle

72
Q

Which molecule regulates the first step of the pentose phosphate pathway?

A

NADPH

73
Q

Enzyme inhibited by NADPH/NADP

A

Glucose 6 phosphate dehydrogenase

74
Q

What does high levels of NADPH/NADP and NAD/NADH indicate

A

That biosynthetic and glycolytic reactions can occur at the same time

75
Q

NADPH is involved in the biosynthesis of which molecules?

A

Fatty acids
Cholesterol (steroids)

76
Q

Ribose 5 phosphate is involved in the synthesis of which molecules?

A

nucleotides (ATP, CoA, NAD, FAD, NADP, RNA, DNA)