W10 - Nitrate Flashcards

1
Q

What happens when there’s an excess amount of aa?

A

Remove amine group + create CHO + fat.

Amine group (NH3) goes in goes into urea cycle = urea –> excreted.

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2
Q

Other than urea + sweat, what are the other methods of excretion of body proteins?

A

Hair

Skin

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3
Q

How are aa recreated?

A

By attaching amine group back onto CHO or fat skeleton.

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4
Q

What does an aa contain?

A

CHON + R group

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5
Q

What non-essential aa is glucogenic + ketogenic?

A

Tyrosine

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6
Q

List the essential ketogenic aa

A

Leucine

Lysine

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7
Q

List the non-essential ketogenic aa

A

There are none

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8
Q

Where into the TCA cycle can glucogenic + then ketogenic aa enter?

A

Glucogenic via:

  • a-ketoglutarate
  • Succinyl-CoA
  • Fumarate
  • Oxaloacetate
  • Pyruvate which together goes into oxaloacetate.

Ketogenic via:

  • Acetyl-CoA
  • Acetoacetyl-CoA
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9
Q

Which aa can enter TCA cycle via a-ketoglutarate?

A

Glucogenic aa:

  • Arginine
  • Glutamate
  • Glutamine
  • Histidine
  • Proline
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10
Q

From the TCA cycle, if we have taken in excess aa and are NOT in a catabolic situation, what can happen to those aa that have entered via the TCA cycle intermediates?

A

aa can leave the TCA cycle + go back through the glucogenic pathway for phosphoenolpyruvate to glucose.

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11
Q

What does the a-keto acid contain?

A

Carbon

Hydrogen

Oxygen

R group

NO nitrogen. Due to amine group having been removed.

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12
Q

What are the 2 ways in which aa NOT used for synthesis of protein or any other nitrogen containing compounds are metabolised?

A

Transamination

Deamination

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13
Q

What is the most common way to remove N from an aa?

A

Transaminate w/ a-keto acid:

aa + a-keto acid a-keto acid + aa

Move the N from aa to a-keto acid.

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14
Q

Equation for deamination

A

aa –> a-keto acid + NH3

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15
Q

Are transaminases freely or reversible or irreversible ?

A

Freely reversible

But depend on substrate availability.

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16
Q

Where does transamination happen?

A

Most tissue including muscle

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17
Q

Equation for the transamination reaction for alanine

A

Alanine + a-keto glutarate — Pyruvate + Glutamate(aa)

By Alanine aminotransferase

REVERSIBLE

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18
Q

Equation for the transamination reaction of aspartate

A

Aspartate + a-keto glutarate – Oxaloacetate + Glutamate(aa)

By Aspartate aminotransferase

REVERSIBLE as is a transamination reaction.

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19
Q

What is aspartate important for?

A

N excretion as it plays a part in the urea cycle.

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20
Q

Where does oxidative deamination occur?

A

Mit matrix of liver

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21
Q

Name a major aa used in oxidative deamination

What equation shows this?

A

Glutamate

Glutamate + NAD NADH + NH4+ + a-ketoglutarate.

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22
Q

Name the only aa that has 2 nitrogens

A

Glutamine

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23
Q

What must happen for the BCAA to get their a-keto acid?

A

Need to be transaminated by BCAT w/ a-ketoglutarate –> glutamate + their corresponding a-keto acids of the BCAA.

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24
Q

After BCAT has acted on the BCAA, what happens to the glutamate produced?

A

Transaminated to form alanine.

Alanine then leaves muscle + taken up by liver.

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25
Q

Once BCAT has acted on the BCAA to produce their corresponding BCAA a-keto acids, what happens to the a-keto-acids?

A

Undergo dehydrogenation by BCKDH.

In which H group is removed.

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26
Q

GLUCOSE-ALANINE CYCLE

  1. What happens to the glycogen in the muscle?
A

Broken down by glycogenolysis to G-6-P.

G-6-P can go further through glycolysis to create pyruvate.

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27
Q

GLUCOSE-ALANINE CYCLE

  1. Once pyruvate has been created from G-6-P in glycolysis, what happens?
A

Pyruvate can transaminate w/ an aa to form alanine.

Alanine from muscle –> blood –> liver.

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28
Q

GLUCOSE-ALANINE CYCLE

  1. What happens once the alanine has been taken up by the liver?
A

Undergoes transamination w/ a-ketoacid glutarate to form:

Glutamate + pyruvate.

    • Pyruvate –> gluconeogensis = glucose –> blood.
    • Glutamate –> deaminated + NH3(lost through urea or used to make plasma proteins).
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29
Q

Define muscle protein breakdown

A

Degradation of polypeptide chains w/in muscle

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30
Q

Define turnover

A

Constant use + restoration of protein

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31
Q

Chemical symbol for nitric oxide

A

NO

1 Nitrogen, 1 oxygen atom

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32
Q

What is the 1st pathway of the nitric oxide pathway?

Briefly what happens?

A

L-arginine

L-arginine + O2 + NADPH – (Nitric oxide synthase) –> NO + NADP + Citrulline

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33
Q

Where can nitric oxide synthesises be found?

A

Bvs

Brain

Muscles

34
Q

What can happen to nitric oxide once its been produced?

A

Can be converted to nitrite (NO2-).

Then to nitrate (NO3-).

35
Q

How can nitrate be converted to nitrite?

A

By certain bacteria in the oral cavity:

Bacterial nitrate reductases.

36
Q

By what can nitrite be converted to nitric oxide in the body?

A

Deoxyhaemoglobin

Respiratory Enzymes

Carbonic anhydrase

37
Q

Other than the L-arginine - Nitric oxide pathway, what is the other nitric oxide pathway?

A

The Nitrate-Nitrite Nitric oxide pathway

38
Q

What does the L-arginine NO pathway require?

A

O2

Nitric oxide synthase

39
Q

By who was nitric oxide 1st identified as a gas?

A

Scientist Joseph Priestley

1772

40
Q

When can nitric oxide be produced in the atmosphere?

A

From the very high temp of a lightning strike.

41
Q

Who established that relaxation of bv only occurs if endothelial cells are present?

A

Robert Fogel

42
Q

Who determined that nitric oxide from nitroglycerine causes smooth muscle to relax?

A

Ferid Murad

43
Q

In what decade was the biological effect of NO established?

A

1980s

44
Q

What are the 3 NOS isoforms utilised in the human body?

A

NOS1 / nNOS

NOS2 / iNOS

NOS3 / eNOS

45
Q

Endothelial or inducible for iNOS

A

Inducible

46
Q

Endothelial or inducible for eNOS

A

Endothelial

47
Q

What does NOS stand for?

A

Nitric oxide synthase

48
Q

What does NADPH stand for?

A

Nicotinamide adenine dinucleotide phosphate

49
Q

What does nNOS stand for?

A

Neuronal NOS

50
Q

Where does nNOS function?

A

Around neurones + supports the nervous system.

51
Q

In what does iNOS (inducible NOS) play a role?

A

In host defence

52
Q

When can macrophages produce NO?

What does this mean?

A

In response to cytokines.

Therefore important as a toxic defence mol vs. infectious organisms.

53
Q

What happens once NO has been produced?

A

Diff into smooth muscle of bv.

54
Q

What happens once the NO has diffused into smooth muscle of bv?

A

Activates soluble guanylyl cyclase (sGC)

55
Q

What does the activation of soluble guanylyl cyclase (sGC)s result in?

A

Increased cyclic guanosine monophosphate (cGMP)

56
Q

What does cGMP activate?

A

Protein kinase (PKG)

57
Q

What happens as a result of protein kinase being activated by cGMP?

A

⬇️ Ca2+

58
Q

Activation of sGC = ⬆️ cGMP = activating Protein kinase = ⬇️ Ca2+

What are the 4 mechanisms via which this happens?

A

Inhibition of voltage gated channels

Activation of plasma membrane Ca+ ATPase

Inhibition of inositol triphosphate receptors (IP^3R)

Activation of sarcoplasmic calcium ATPase

59
Q

What happens to NO as we age?

A

Becomes impaired

= ⬇️ in endothelial function which can lead to adverse CV events

60
Q

What are the foods highest in nitrate?

A

Green leafy veg

i.e beetroot, spinach, lettuce….

61
Q

What does the nitrate availability of the same vegetables depend on?

A

Time of year

Use of nitrate based fertilisers

Transport conditions

Storage conditions

62
Q

What is generally found in people who consume a nitrate rich diet?

A

Lower bp

63
Q

Other than food, what can another source of nitrate be?

A

H20

64
Q

Describe the nitrate journey through the body after the consumption of a high nitrate drink i.e beetroot juice

A

5% of it is recycled to the saliva.

20% of nitrate in saliva is converted to nitrite by oral commensal bacteria on the tongue.

5% swallowed into stomach + provides for nitric oxide activities.

65
Q

Out of the total 100% nitrate ingested, what % is processed + used in the body and what % is excreted in urine?

A

Body = 25%

Urine = 75%

66
Q

What can NO be produced in the stomach for?

A

Local vasodilation

Mucus formation

Anti-microbial activity

67
Q

What are N-nitrosoamines?

A

Derivatives of secondary amines which have a nitroso (-NO) group attached to nitrogen.

68
Q

How are N-nitrosoamines formed?

A

By the reaction of nitrite w/ secondary amines.

69
Q

Once the 5% nitrate has been swallowed into stomach, what are the local + systemic actions in the forms of?

A

Nitric oxide

N-nitrosoamines

Nitrite

S-nitrosothiols

70
Q

What are S-nitrosothiols?

A

Nitroso group attached to a sulphur atom of a thiol.

71
Q

How long after ingestion is there a peak in the conc. of plasma nitrate in the blood plasma?

A

~1hr

72
Q

Why do we need nitrate to be concentrated in the saliva?

A

Due to the symbiotic relationship with the bacteria in our mouths.

73
Q

What part of the NO pathway is oral bacteria important for?

A

Nitrate-nitrite NO pathway

74
Q

Why has meat got a much higher nitrite content than any whole vegetable?

A

Due to addition of a preservative called sodium nitrite that extends shelf life + enhances flavour.

75
Q

What did the WHO recommend the upper limit of daily nitrate concentration to be?

A

3.7 mg/kg of body mass per day

76
Q

What did the WHO recommend the upper limit of daily nitrite concentration to be?

A

0.07 mg/kg of body mass per day

77
Q

Why do guidelines exist for the consumption of nitrates?

A

Due to research linking nitrate consumption of meat w/ colorectal cancer.

78
Q

What is the process of Nitrosation?

A

Process of converting organic compounds into nitroso derivatives.

79
Q

What can Nitrosation produce?

A

N-aklyl nitrosoamine compounds.

These can cause DNA damage + formation of colon carcinoma.

80
Q

What method is there to assess the endothelial linings ability to produce nitric oxide?

A

Flow mediated dilation

81
Q

What are the 8 steps to flow mediated dilation?

A
  1. Baseline measurement (can be up to 1 min)
  2. Inflate the cuff
  3. Ischaemia happens below the cuff so the vasculature dilates = ⬇️ vascular resistance
  4. Cuff is released after 5 mins
  5. Dramatic ⬆️ in bf
  6. Shear stress
  7. Endothelium releases vasodilators + NO
  8. Healthy artery dilates