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Metabolic Pathways Flashcards

1
Q

GLUT 2 is located in which Tissues?

What is the kM of GLUT 2 transporters?

Are these Insulin responsive?

A
  1. Liver, B-Islet Cells of Pancreas, Kidney, Small Intestine
  2. 12mM
  3. No
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2
Q

What are the 4 processes involved in glucose homeostasis?

A
  1. Dietary carbohydrate intake 2. Hormone action 3. Tissue interrelationships 4. Metabolic pathways
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3
Q

name the pathway these enzymes belong to

A
  1. Glycogenolysis
  2. Glycogenesis
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4
Q

Pyruvate Kinase

  1. Is inhibited by ____ and ______
  2. Is stimulated by _______ in a feed forward mechanism
  3. The activity is also regulated by covalent modulation through (What Hormone) which leads to phosphorylation and subsequent inhibition of pyruvate kinase.
A
  1. ATP & Alanine
  2. Fructose 1,6 bisphosphate
  3. Glucagon
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5
Q

What substrate feeds forward to stimulate Pyruvate Kinase (the last step in glycolysis)

A

Fructose 1,6-bisphosphate is the Allosteric effector

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6
Q

What is the irreversible mitochondrial enzyme which turns Pyruvate into AcetylCoA?

A

Pyruvate dehydrogenase

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7
Q

What do you get if you add an amine group to Pyruvate?

A

Alanine

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8
Q

What two major substrates limit glycolysis?

A

Glucose and NAD+

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9
Q

What are the 3 enzymes involved in the regulatory steps of Glycolysis?

A

Hexokinase, PFK1, Pyruvate Kinase

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10
Q

During Extreme starvation the Brain and nervous system (in humans) can use ______ for up to 30% of its ATP supply.

ATP production from Glucose in the Brain and Nervous system is always utilised anaerobically/Aerobically?

A
  1. Ketone bodies
  2. Aerobically
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11
Q

Which GLUT Transporters are in the brain?

What is their Km?

Are they insulin responsive?

A
  1. GLUT 1 & 3
  2. GLUT 1 = 1mM
    GLUT 3 = <1mM
  3. No
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12
Q

What does the hormone do and what tissues does it do it too? 1) Insulin 2) Glucagon

A

1) insulin tells the muscle and adipose cells that there is excess glucose in the blood, and they are allowed to store it. 2) Glucagon tells the liver there is not enough glucose in the blood, so the liver responds by mobilising glucose stored within itself

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13
Q

Give a Summary of Glycolysis

  • Give the differences in ATP in the investment phase between Glucose and Glycogen
  • How much ATP is made during the payoff phase
  • For a Net gain of how much ATP?
  • How is there enough NAD+ for Glycolysis in anerobic conditions to continue?
A
  1. Glucose uses 2 ATP, Glycogen only uses 1 ATP
  2. 4 ATP is produced in the Payoff Phase
  3. Net gain of 2 ATP if starting with Glucose
  4. NAD+ is used (turned into NADH) up during glycolysis however in anerobic conditions, pyruvate is turned into Lactate and that requires NADH which is in turn turned back into NAD+
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14
Q

What is the name of C18:2?

What is its Omega Number

A

Linoleic Acid

N-6

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15
Q

Where does Glycolysis happen

A

In the soluble cytoplasm (cytosol) of the cell

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16
Q

What does Glutaminase do?

A
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17
Q

What are the two main tissues which are insulin responsive?

A

Muscle Adipose Tissue

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18
Q

How many molecules of ATP does Glycolysis create from one molecule of Glucose

A

2 ATP is produced from each molecule of Glucose. Investment phase uses 2ATP Payoff phase produces 4 ATP

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19
Q

What is the rate limiting step of Glycogenolysis`

A
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20
Q

Acetyl CoA is converted from Pyruvate with the help of which enzyme?

Lactate is converted from Pyruvate with the help of which enzyme?

A
  1. pyruvate dehydrogenase
  2. Lactate Dehydrogenase
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21
Q

Where is Glucokinase found?

And what is it inhibited by?

What is its Km?

Liver Hexokinase is ____ Order where Glucokinase is ____ Order under conditions of high clucose intake.

A
  1. Liver
  2. Glucose-6-Phosphate
  3. 12mM (hexokinase is 20uM)
  4. Hexokinase is Zero Order
    Glucokinase is First Order
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22
Q

Name the 3 important transaminases and what they do.

A
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23
Q

What are the Enzymatic “Key Players” in removing Amino-Nitrogen from Amino Acids?

A
  1. Transamination, all tissues but mainly liver-
    • Alanine Transaminase
    • Aspartate Transaminase
    • Glutamate Transaminase
  2. Direct Deamination-
    • Glutamate dehydrogenase (liver)
    • Glutaminase (Kidney & Liver)
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24
Q

What hormone is involved in inhibition of Pyruvate Kinase (last step of glycolysis)

A

Glucagon (via cAMP dependant protein kinase) Allosteric inhibiting is cause by ATP & Alanine

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25
Q

Name the Obligatory Quartet and their cellular locations

A
  1. Pyruvate Carboxylase (PC, a mitochondrial enzyme)
  2. Phospoenolpyruvate carboxykinase (PEPCK, an inducible enzyme mainly present in the cytosol)
  3. Fructose-1,6 bisphosphatase (F-1,6bisPase) present in the cytosol and which is the major regulatory enzyme determining the overall rate of gluconegenesis
  4. glucose-6-phosphase present in the smooth endoplasmic reticulum which releases the phosphate from G-6-P thereby allowing the glucose to pass across the pass across the plasma membrane tin to the blood
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26
Q

What is Hyperglycaemia

A

Extended elevation >= 10mM As in uncontrolled diabetes can lead to glycosylatio. Of proteins (eg crystalline of lens)

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27
Q

At Homeostasis each GLUT transporter is at what order of kenetics?

A
  • GLUT 1 - Zero Order
  • GLUT 2 - First Order
  • GLUT 3 - Zero Order
  • GLUT 4 - First Order
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28
Q

What are the two pathsways of Protein Degradation?

A
  1. Ubiquitin Proteasome pathway which is non-lysosomal and ATP dependant.
    1. the major route of degradation of muscle protein in mammals that releases Amino Acids
    2. involved in the degradation of crictical regulatory proteins
    3. One of the crictical functions of this pathwayis the rapid degradation of highly abnormal proteinsas may arise by mutations, post synthetic damage, or genetic engineering
    4. Up-regulated during acut wasting desease
  2. Lysosomal Degradation of Enzymes
    1. Major pathway in the liver
    2. Range of cathepsin enzymes (A-F)
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29
Q

What 2 tissues is glycogen stored?

What is the Function of the Function of the Glycogen in each of these stores?

A
  1. Liver (6%of Liver wet weight) and Muscle (1-2%)
  2. Function
    1. Liver - Storage and Export of glucose; maintains blood glucose, Depleted after 12-18 hours fasting. ESSENTIAL FOR GLUCOSE HOMEOSTASIS
    2. Muscle - Fuels glycolysis within muscle only. Depleted through prolonged vigorous exercise. NOT ESSENTIAL FOR GLUCOSE HOMEOSTASIS. Used for high intesity exercise.
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30
Q

What does an enzyme with the name Phosphorylase do?

A

It’s an enzyme which adds phosphate using inorganic phosphate [Pi] as a phosphate donor Eg. Glycogen phosphorylase

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31
Q

What is an Allosteric Effector?

A

Binds to an enzyme at a location other than the active site. This binding may stimulate or inhibit the binding of the enzyme to the substrate. Eg. cAMP

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32
Q

What is the Normal Plasma Glucose level for ruminants?

A

3-4mM

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33
Q

What does Glutamate Dehydrogenase do?

A
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34
Q

In what part of the cell do all the enzymic steps of glycolysis proceed in?

A

In the Cytosol

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35
Q

What does a “Kinase” do And give an example

A

Kinase is an enzyme which cleaves a phosphate from ATP and adds it to the recipient Eg. Protein Kinase

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36
Q

What are the 3 regulatory enzymes of Glycolysis?

A
  • Hexokinase
  • Phosphofructokinase 1 (PFK1)
  • Pyruvate Kinase
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37
Q

What is Hypoglycaemia

A

Less than half the normal plasma glucose levels. Fuel deprivation for the brain etc 2mM is bad 1mM is real bad

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38
Q

Where in the body does Gluconeogenesis occur?

A

Liver and to a lesser extent kidneys.

39
Q

What does an enzyme with the name Phosphatase do?

A

An enzyme that removed phosphate as inorganic phosphate [Pi] Eg. Protein Phosphatase

40
Q

How is Glycogenolysis and Glycogenesis regulated (reciprical regulation)?

41
Q

What is Covalent Modulation

A

Is when either a “Kinase adds” or a “Phosphatase cleaves” a phosphate molecule to/from an enzyme which may stimulate or inhibit the substrate binding to the enzyme

42
Q

What is the rate limiting step in Glycogenesis?

43
Q

In high protiens diets what metabolic pathway would be the major source of blood glucose?

A

Gluconeogenesis

44
Q

What is the major regulation point of Gluconeogenesis?

A

At the enzymic steps between fructose 1,6 Bisphosphate and Fructose 6-Phosphate

45
Q

During starvation what is the basis for long-term glucose homeostasis in all mammalian species?

A

Gluconeogensis

46
Q
  1. What is the ATP cost for each molecule of urea?
  2. Where in the body does the Urea cycle occur?
A
  1. 4ATP
  2. Liver
47
Q

Where in the cell does the Pentose Phosphate Patbhway occur

A

Cytosol of all cells.

48
Q

Non-carbohydrate carbon sources for glucose synthesis

There are four major types of compounds used in the synthesis of glucose via gluconeogenesis, what are they?

A
  1. Lactate (lactic Acid) from muscle
  2. Glycerol from white adipose tissue
  3. amino acids from protein degradation (mainly from muscle)
  4. Propionate from rumen fermentation
49
Q
  1. What are the hormonal regulators of Lysosmal protein degradation
  2. What are the nutritionalreglators of Lysosmal Protein Degradation?
A
  1. Hormonal
    • ++Glucagon
    • – Insulin
      • Glucocorticoids
  2. Nutritional
    • – Asparagine
    • Glutamine
50
Q

How do we turn off cAMP?

A

With Insulin. It turns on Phosphodiesterase which turns off cAMP

51
Q

What is the name of C18:3

What is its Omega Number?

A

Linolenic Acid

N-3

52
Q

Why does Erythrocytes have no capacity to use fats or amino acids?

A

Erythrocytes are GLUT 1 and do not contain mitochondria, therefore are completely dependant on glucose for energy supply.

The production of ATP from Fats and amino acids are done in the mitochondria, and therefor Erythocytes have no capacity to use these.

53
Q

What does Phosphofructokinase (PFK1) do?

A

It cleaves a phosphate from ATP and adds it to Fructose 6-Phosphate turning it into Fructose 1, 6-Bisphosphate during the investment phase of glycolysis. This is the rate limiting step

54
Q

What is the name of C18:1?

What is its Omega Number?

A

Oleic Acid

N-9

55
Q

What is the name of C18:0

A

Stearic Acid

56
Q

1) What is the function of Glycolysis? 2) what is the end product of Glycolysis? 3) What is Glycolysis dependant on?

A

1) Catabolism of carbohydrates as glucose to produce energy in the form of ATP 2) Pyruvate (Keto acid) 3) NAD+ dependant (electron acceptor)

57
Q

What is the enzyme which is the key rate limiting step in Glycolysis?

A

Phosphofructokinase (PFK1)

58
Q

Name 7 tissues dependent on glycolysis

A
  • Brain
  • Erythrocytes
  • Type II skeletal muscells
  • Foetus
  • Renal medulla
  • Retina
  • Skin
59
Q

In ruminants what Volatile Fatty Acid (VFA) is converted into Glucose by what process?

A

Propionate

Gluconeogenesis

60
Q

What is the Allosteric effector that massively speeds up Phosphofructokinase (PFK1)?

A

Fructose 2,6-bisphosphate

61
Q

What enzyme is needed to produce the Allosteric effector (Fructose 2,6-bisphosphate) to speed up glycolysis through the rate limiting step?

A

PFK2 And Fructose 2,6-bisPase slows it down. The rate limiting step is Fructose 6-Phosphate —- Fructose 1,6-Bisphosphate through the use of Phosphofructokinase (PFK1)

62
Q

What does Gluconeogenesis actually mean?

A

Synthesis of new glucose (if read backwards)

63
Q

In what tissues does Gluconeogenesis occur

A

Liver >90%, Kidney <10%

64
Q

PFK1 (Phosphofructokinase 1)

  1. Is inhibited by what 3 allosteric effectors?
  2. What are the positive effectors that stimulate activity?
A
  1. ATP, citrate and H+
  2. AMP and Fructose 2,6-bisphosphate
65
Q

What are the main two functions of the Pentose Phosphate Pathway?

A
  1. an oxidative pathway that produces NADPH for reductive synthesis eg for fatty acid systhesis and steroid hormone systhesis
  2. a non-oxidative pathway that produces ribose 5-phosphate for systhesis of nucleotides
66
Q

What is Glycolysis do?

A

It turns Glucose into Pyruvate

67
Q
  1. What are the 2 Ketogenic Amino acids
  2. What are the 4 Glucogenic/ketogenic Amino Acids
A
  1. Leucine, Lysine
  2. Isoleucine, Phenylalanine, Tryosine, Tryptophan
68
Q

What tissues are GLUT 4 transporters found?

What is their Km?

Are they insulin responsive?

A
  1. Muscle, Heart, Adipose Tissue
  2. 5mM
  3. Yes
69
Q

What is the name of C16:0

A

Palmitic Acid

70
Q
  1. How is glycerol produced?
A
  1. From the breakdown of Triacylglycerols in white adipose tissue
71
Q

When is glycoilysis important for ATP production?

A
  • High carbohydrate intake
  • Stress
  • Exercise
72
Q

In the Urea cycle where is the nitrogen sourced from?

A
  1. Glutamate
  2. Aspartate
  3. Glutamine
73
Q

What is the metabolic importance of the TCA cycle?

A

final pathway for oxidising carbo, lipid & protein

  • major role in gluconeogenesis, transamination, deamination, & lipogenesis (important in liver)
74
Q

What are the direct products of the TCA cycle?

75
Q

What reactants does Oxidative Phosphorylation require and what is its products?

76
Q

The TCA cycle produces NADH and FADH2, via oxidative phosphorylation how much ATP does each provide?

77
Q

What are the 2 types of NADH shuttles?

A
  • Glycerophosphate shuttle
  • Malate/aspartate shuttle
78
Q

Explain the glycerophosphate shuttle

79
Q

Explain the Malate/Aspartate Shuttle

80
Q

What is the total ATP produced Areobically from 1 molecule of Glucose

81
Q

Anaerobic v’s Aerobic respiration ATP production?

How much ATP produced per glucose molecule?

Is Aerobic Respiration faster or slower than Anaerobic and if so how much faster?

82
Q

What is Lipolysis?

A

Conversion of TAG into NEFA’s

83
Q

Name the 3 places Lipolysis happens

A
  1. Adipose Tissue
  2. Capillary Wall
  3. Intracellularly
84
Q

What Enzyme controls Lipolysis in Adipose Tissue?

A

Hormone Sensitive Lipase

85
Q

Enzyme Hormone Sensitive Lipase works on what reagent, and gives what products?

86
Q

How is Hormone Sensetive Lipase Activated?

A

During starvation Glucogon is released, which with the help of Adenyl Cyclase converts ATP to cAMP.

cAMP dependent Protien Kinase then converts Inactive Lipase (using ATP) into active Lipase

87
Q

In the fed state where does Lipolysis happen?

And what is the enzyme?

A

Capillary Walls

Lipoprotein lipase

88
Q

Name the 4 Lipoproteins and their transport function

89
Q

If we oxidise C16:0 what is our total ATP agains/Losses?

90
Q
  1. 1 round of beta oxidation gives what products?
  2. How much ATP is generated for each of these products
  3. Acetyl CoA feeds into the TCA cycle, how much ATP is generated from each of the TCA cycles products from 1 Molecule of Acetyl CoA
A
  1. Beta Oxidation gives
    • 1 x Acetyl CoA
    • 1 x NADH
    • 1 x FADH2
  2. ATP Generated
    • Acetyl CoA = 10ATP
    • NADH = 2.5ATP
    • FADH2 = 1.5ATP
91
Q

What controls Beta Oxidation

92
Q

What isomer (Cis or Trans) do Unsaturated Fatty Acids need to be in for Oxidation?

A

Trans (which needs Isomerase Enzyme to change from cis to trans)

93
Q
  1. How does the Body avoid the toxic effects of too much NEFA?
  2. In what tissues does this occur?
A
  1. Through Hepatic Keytogenisis
  2. Liver Mitacondria, (some in kidney and Rumen Wall)
94
Q

Control of Keytogenisis

VET272 (3 decks)

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