Nitrogen Metabolism Flashcards
Quantify the inputs and outputs that represent daily nitrogen balance
6kg~ of protein in the body
100g intake (contains 16.5g nitrogen) and 100g lost (100g in, 100g out = nitrogen balance)
4% turnover per day : which means protein are getting broken down into amino acids and then normally those amino acids being used to rebuild new proteins/ proteins are broken down and rebuilt one way or another
muscle is 2% turnover of protein, cells lining our intestines, our gastrointestinal tract = 15% protein turnover (massive turnover of protein)
when do we process amino acids
During normal protein turnover
– The amino acids released from protein turn over is reassembled into protein with function or oxidation of amine group (aa can’t be stored)
* Oxidised in tissue or into bloodstream
During starvation
– insulin stimulates high proteolysis = break down of proteins into aa
When diet is rich in protein
– Surplus amino acids that need to be disposed
Describe the basic principles of amino acid processing
– Liver important : first place amino acids go from intestine
it comes to detoxifying the ammonia in the amen groups.
So the urea cycle is primarily in the liver dealing with the carbon backbones/skeleton, that
is, it will either perform glucon, agenesis, lipogenesis or oxidise
those backbones into CO2 and the CREB cycle.
- Processing of amine groups
* liver works to detoxify ammonia from amine grops = urea synthesis - Conversion of amino acid backbones
* used in Gluconeogenesis, lipogenesis, oxidise backbones into CO2 and Krebs Cycle
* Glucogenic amino acids can be converted into intermediates of the citric acid cycle or gluconeogenesis, leading to the production of glucose or other carbohydrates. Ketogenic amino acids can be converted into ketone bodies or acetyl-CoA, which can be used for energy production via ketogenesis or the citric acid cycle.
Understand the significance of amino acid degradation enzymes having a high Km:
Degradation enzymes that break proteins into aas have very high Km, which means sensitive to changes in [substrate]
= more aa, enzymes will immediately do somthing with it
– Not ‘controlled’
– Only affected by [amino acid]
– So excess amino acids are degraded
When amino acid levels are high, the enzymes are saturated and the pathway is active.
When amino acid levels are low, the enzymes are less active, conserving amino acids for protein synthesis or other metabolic processes.
use of branched and unbranched chain aa after feeding
after feeding :
1. aa enters through the Portal vein (into liver)
contains ~ 20% branched chain amino acids (Leucine, isoleucine, valine)
- Hepatic vein (out of liver)
– mixture that leaves the liver contains 70% branched chain amino acids
* liver has preferentially kept the non-branched chain
amino acids to itself - Arterial circulation
– Same as what went out of the liver - Veins from muscle
– Branched chain amino acids removed (all taken up and used by muscles)
– Muscle uses a lot of branched chain amino acids for energy
processing of aa during starvation
low blood insulin concentration/ Hypoinsulinemia = stimulate proteolysis ( the breakdown
of proteins )
lots of amino acids are released (disproportionately high amounts of alanine & glutamine are released)
not many branched chain amino acids because they fuel muscles
glucose-alanine cycle
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Glucose to Pyruvate in Muscle Cells:
- Glucose is taken up by muscle cells –> pyruvate (= produces ATP)
-
Pyruvate to Alanine:
- In the presence of excess amino acids, pyruvate reacts with an amino group (pyruvate + amine group) from an amino acid (usually glutamate) to form alanine.
-
Alanine Transport to the Liver:
- Alanine is released into the bloodstream and transported to the liver.
-
Alanine Breakdown in the Liver:
- In the liver, alanine is taken up by hepatocytes and undergoes reverse transamination. The amino group of alanine is transferred to α-ketoglutarate, forming glutamate and alanine –> pyruvate.
-
Glucose Regeneration in the Liver:
- The pyruvate generated from alanine breakdown in the liver can enter the gluconeogenesis pathway.
central role of transaminases in the shuffling of amino groups during amino acid processing
an amino acid transfers its amine group to an acceptor (pyruvate, a-ketoglutarate and oxaloacetate) and becomes a-keto acid using amino-transferase
- Pyruvate + amine group = alanine
- 2-oxo glutarate + amine group = glutamate
- Oxaloacetate + amine group = aspartate
amine groups are carried and fed into urea cycle
Summarize the key features of the urea cycle:
The Urea Cycle
– amine groups that are passed onto glutamate/alanine are fed into the urea cycle
- it takes ATP to detoxify that amine group.
–>lead to the release of ammonia (NH3) = converted into urea for excretion from the body.
* ornithine acts like oxaloacetate in the krebs cycle
- Different steps of the urea cycle occur in different cellular compartments. For example, the initial steps occur in the mitochondria, while later steps occur in the cytoplasm. This compartmentation allows for efficient coordination of the reactions and prevents the accumulation of toxic intermediates in the cell.
processing skeletons
carbon skeletons can fuel krebs (ketogenic) or gluconeogenesis (glucogenic)
glucogenic : can fuel glucose formation/ gluconeogenesismake glycolysis intermediate
ketogenic : only make acetyl CoA
Appreciate the reasons why most amino acids need to be in the human diet
amino acids synthesis:
* pathways are linked to Glycolysis/Krebs/Pentose Phosphate Pathway
* we can’t do most of the metabolism.
–> rely on bacteria and other organisms to to do
a lot of this synthesising for us, and we consume all of these amino acids in our diet.
nonessential amino acids
alanine
asparagine
aspartate
glutamate
serine
essential aminoacids
cannot be synthesised by body, from diet
–> you are lacking in one amino acid, you may not be able to make an entire protein
– can’t do protein synthesis
products that need amino acids
- Creatine
– Non-peptide hormones
(adrenalin)
– Nucleotides
purine syntehsis
purines = essential components of DNA, RNA, and ATP.
takes a lot of amino acids and other compounds to come
together just to build one purine.
it takes a lot of different amino acids and a lot of enzymes and a lot of ATP just to build one purine base to put in your DNA
–> very complex process : rely on salvage pathways to recycle and salvage preformed purine bases and nucleosides
Inhibitors of purine synthesis disrupt the production of purine nucleotides, leading to a decrease in cellular ATP and GTP levels.
–> impair critical cellular functions that rely on ATP and GTP, including energy metabolism, DNA replication, and protein synthesis.
–> Since purine nucleotides are essential for DNA synthesis and cell division
= inhibition of purine synthesis can inhibit cell growth and proliferation.
cancer cells (rapidly dividing cells that require billions of purines and pyrimidine bases) where the demand for purines is high.
–> can activate apoptotic pathways, leading to cell death and elimination of damaged or dysfunctional cells.
