W10 - Nitrate Flashcards
What happens when there’s an excess amount of aa?
Remove amine group + create CHO + fat.
Amine group (NH3) goes in goes into urea cycle = urea –> excreted.
Other than urea + sweat, what are the other methods of excretion of body proteins?
Hair
Skin
How are aa recreated?
By attaching amine group back onto CHO or fat skeleton.
What does an aa contain?
CHON + R group
What non-essential aa is glucogenic + ketogenic?
Tyrosine
List the essential ketogenic aa
Leucine
Lysine
List the non-essential ketogenic aa
There are none
Where into the TCA cycle can glucogenic + then ketogenic aa enter?
Glucogenic via:
- a-ketoglutarate
- Succinyl-CoA
- Fumarate
- Oxaloacetate
- Pyruvate which together goes into oxaloacetate.
Ketogenic via:
- Acetyl-CoA
- Acetoacetyl-CoA
Which aa can enter TCA cycle via a-ketoglutarate?
Glucogenic aa:
- Arginine
- Glutamate
- Glutamine
- Histidine
- Proline
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?
aa can leave the TCA cycle + go back through the glucogenic pathway for phosphoenolpyruvate to glucose.
What does the a-keto acid contain?
Carbon
Hydrogen
Oxygen
R group
NO nitrogen. Due to amine group having been removed.
What are the 2 ways in which aa NOT used for synthesis of protein or any other nitrogen containing compounds are metabolised?
Transamination
Deamination
What is the most common way to remove N from an aa?
Transaminate w/ a-keto acid:
aa + a-keto acid a-keto acid + aa
Move the N from aa to a-keto acid.
Equation for deamination
aa –> a-keto acid + NH3
Are transaminases freely or reversible or irreversible ?
Freely reversible
But depend on substrate availability.
Where does transamination happen?
Most tissue including muscle
Equation for the transamination reaction for alanine
Alanine + a-keto glutarate — Pyruvate + Glutamate(aa)
By Alanine aminotransferase
REVERSIBLE
Equation for the transamination reaction of aspartate
Aspartate + a-keto glutarate – Oxaloacetate + Glutamate(aa)
By Aspartate aminotransferase
REVERSIBLE as is a transamination reaction.
What is aspartate important for?
N excretion as it plays a part in the urea cycle.
Where does oxidative deamination occur?
Mit matrix of liver
Name a major aa used in oxidative deamination
What equation shows this?
Glutamate
Glutamate + NAD NADH + NH4+ + a-ketoglutarate.
Name the only aa that has 2 nitrogens
Glutamine
What must happen for the BCAA to get their a-keto acid?
Need to be transaminated by BCAT w/ a-ketoglutarate –> glutamate + their corresponding a-keto acids of the BCAA.
After BCAT has acted on the BCAA, what happens to the glutamate produced?
Transaminated to form alanine.
Alanine then leaves muscle + taken up by liver.
Once BCAT has acted on the BCAA to produce their corresponding BCAA a-keto acids, what happens to the a-keto-acids?
Undergo dehydrogenation by BCKDH.
In which H group is removed.
GLUCOSE-ALANINE CYCLE
- What happens to the glycogen in the muscle?
Broken down by glycogenolysis to G-6-P.
G-6-P can go further through glycolysis to create pyruvate.
GLUCOSE-ALANINE CYCLE
- Once pyruvate has been created from G-6-P in glycolysis, what happens?
Pyruvate can transaminate w/ an aa to form alanine.
Alanine from muscle –> blood –> liver.
GLUCOSE-ALANINE CYCLE
- What happens once the alanine has been taken up by the liver?
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).
Define muscle protein breakdown
Degradation of polypeptide chains w/in muscle
Define turnover
Constant use + restoration of protein
Chemical symbol for nitric oxide
NO
1 Nitrogen, 1 oxygen atom
What is the 1st pathway of the nitric oxide pathway?
Briefly what happens?
L-arginine
L-arginine + O2 + NADPH – (Nitric oxide synthase) –> NO + NADP + Citrulline
Where can nitric oxide synthesises be found?
Bvs
Brain
Muscles
What can happen to nitric oxide once its been produced?
Can be converted to nitrite (NO2-).
Then to nitrate (NO3-).
How can nitrate be converted to nitrite?
By certain bacteria in the oral cavity:
Bacterial nitrate reductases.
By what can nitrite be converted to nitric oxide in the body?
Deoxyhaemoglobin
Respiratory Enzymes
Carbonic anhydrase
Other than the L-arginine - Nitric oxide pathway, what is the other nitric oxide pathway?
The Nitrate-Nitrite Nitric oxide pathway
What does the L-arginine NO pathway require?
O2
Nitric oxide synthase
By who was nitric oxide 1st identified as a gas?
Scientist Joseph Priestley
1772
When can nitric oxide be produced in the atmosphere?
From the very high temp of a lightning strike.
Who established that relaxation of bv only occurs if endothelial cells are present?
Robert Fogel
Who determined that nitric oxide from nitroglycerine causes smooth muscle to relax?
Ferid Murad
In what decade was the biological effect of NO established?
1980s
What are the 3 NOS isoforms utilised in the human body?
NOS1 / nNOS
NOS2 / iNOS
NOS3 / eNOS
Endothelial or inducible for iNOS
Inducible
Endothelial or inducible for eNOS
Endothelial
What does NOS stand for?
Nitric oxide synthase
What does NADPH stand for?
Nicotinamide adenine dinucleotide phosphate
What does nNOS stand for?
Neuronal NOS
Where does nNOS function?
Around neurones + supports the nervous system.
In what does iNOS (inducible NOS) play a role?
In host defence
When can macrophages produce NO?
What does this mean?
In response to cytokines.
Therefore important as a toxic defence mol vs. infectious organisms.
What happens once NO has been produced?
Diff into smooth muscle of bv.
What happens once the NO has diffused into smooth muscle of bv?
Activates soluble guanylyl cyclase (sGC)
What does the activation of soluble guanylyl cyclase (sGC)s result in?
Increased cyclic guanosine monophosphate (cGMP)
What does cGMP activate?
Protein kinase (PKG)
What happens as a result of protein kinase being activated by cGMP?
⬇️ Ca2+
Activation of sGC = ⬆️ cGMP = activating Protein kinase = ⬇️ Ca2+
What are the 4 mechanisms via which this happens?
Inhibition of voltage gated channels
Activation of plasma membrane Ca+ ATPase
Inhibition of inositol triphosphate receptors (IP^3R)
Activation of sarcoplasmic calcium ATPase
What happens to NO as we age?
Becomes impaired
= ⬇️ in endothelial function which can lead to adverse CV events
What are the foods highest in nitrate?
Green leafy veg
i.e beetroot, spinach, lettuce….
What does the nitrate availability of the same vegetables depend on?
Time of year
Use of nitrate based fertilisers
Transport conditions
Storage conditions
What is generally found in people who consume a nitrate rich diet?
Lower bp
Other than food, what can another source of nitrate be?
H20
Describe the nitrate journey through the body after the consumption of a high nitrate drink i.e beetroot juice
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.
Out of the total 100% nitrate ingested, what % is processed + used in the body and what % is excreted in urine?
Body = 25%
Urine = 75%
What can NO be produced in the stomach for?
Local vasodilation
Mucus formation
Anti-microbial activity
What are N-nitrosoamines?
Derivatives of secondary amines which have a nitroso (-NO) group attached to nitrogen.
How are N-nitrosoamines formed?
By the reaction of nitrite w/ secondary amines.
Once the 5% nitrate has been swallowed into stomach, what are the local + systemic actions in the forms of?
Nitric oxide
N-nitrosoamines
Nitrite
S-nitrosothiols
What are S-nitrosothiols?
Nitroso group attached to a sulphur atom of a thiol.
How long after ingestion is there a peak in the conc. of plasma nitrate in the blood plasma?
~1hr
Why do we need nitrate to be concentrated in the saliva?
Due to the symbiotic relationship with the bacteria in our mouths.
What part of the NO pathway is oral bacteria important for?
Nitrate-nitrite NO pathway
Why has meat got a much higher nitrite content than any whole vegetable?
Due to addition of a preservative called sodium nitrite that extends shelf life + enhances flavour.
What did the WHO recommend the upper limit of daily nitrate concentration to be?
3.7 mg/kg of body mass per day
What did the WHO recommend the upper limit of daily nitrite concentration to be?
0.07 mg/kg of body mass per day
Why do guidelines exist for the consumption of nitrates?
Due to research linking nitrate consumption of meat w/ colorectal cancer.
What is the process of Nitrosation?
Process of converting organic compounds into nitroso derivatives.
What can Nitrosation produce?
N-aklyl nitrosoamine compounds.
These can cause DNA damage + formation of colon carcinoma.
What method is there to assess the endothelial linings ability to produce nitric oxide?
Flow mediated dilation
What are the 8 steps to flow mediated dilation?
- Baseline measurement (can be up to 1 min)
- Inflate the cuff
- Ischaemia happens below the cuff so the vasculature dilates = ⬇️ vascular resistance
- Cuff is released after 5 mins
- Dramatic ⬆️ in bf
- Shear stress
- Endothelium releases vasodilators + NO
- Healthy artery dilates
