Nitrogen Metabolism Flashcards
What are the pairs to know?
Glutamate and alpha ketoglutarate
Alanine and pyruvate
Aspartate and oxaloacetate
How is ammonium transported to the liver from muscle cells?
Through the glutamate-alanine cycle
What is the rate-limiting step of urea synthesis?
Carbamoyl Phosphate Synthetase I (converted of bicarbonate and ammonium to carbamoyl phosphate)
Regulators of CPS I
N-acetylglutamate is an allosteric activator
it is required for CPS I activity, therefore it is an obligate activator
How is N-acetylglutamate formed?
from Acetyl CoA and glutamate by N-acetylglutamate synthase, which is a reaction stimulated by Arginine
Function of Arginase
Cleaves arginine, using water, to create urea and ornithine (to be recycled)
What link the urea cycle and CAC?
Aspartate and Fumarate
Where does the urea cycle occur?
Almost exclusively in the liver, in both the cytosol and mitochondria
What are the precursors of urea?
NH4+, CO2, and aspartate (which donates an amino group)
What are poryphyrins?
Cyclic compounds that bind primarily Fe2+ or Fe3+; the most common is heme which binds a single Fe2+ and it is a prosthetic group for hemoglobin, cytochromes, and some enzymes; all carbon and nitrogen atoms in the structure are derived from glycine and succinyl CoA
What is acute intermittent porphyria?
a heterozygous genetic disease which includes abdominal pain, neuropsychiatric problems, motor weakness; occurs because of starvation or insufficient carbohydrate
What is porphyria cutanea tarda?
disease which causes red urine, strong teeth fluorescence under UV light, skin sensitivity towards light, anemia due to insufficient heme
Name the catelcholamines and what they’re synthesized from
dopamine, norepinephrine, and epinephrine, all synthesized from tyrosine; they all occur in the same pathway, so to synthesize a singular product you will need to inhibit the succeeding steps
What is histamine?
A molecule that mediates the allergic response and is a strong vasodilator; it is synthesized by decarboxylating histidine; also used in gastric acid secretion (allows cAMP to move H pump to the sruface
What is seratonin?
A molecule that mediates pain perception, sleep, temperature, blood pressure, appetite, sense of well-being (converted to melatonin in the brain); melatonin maintains circadian rhythm; it is found in abudnance in intestinal mucosa, and a little in CNS where it is a neurotransmitter; seratonin is synthesized from tryptophan
What is creatine?
A high-energy compound found in muscle; it’s its phosphorylated form (phosphocreatine or creatine phosphate) can be used to replenish ATP levels for a few minutes; it is synthesized from glycine, guanidino group of arginine, and methionine
What are the coenzymes of Glu DH?
NAD or NADP
How do plants and microoranisms assimilate nitrogen?
They combined ammonium to a-KG to make glutamate via glutamate dehydrogenase (and NADPH+H); then, ammonium and glutamate are combined to make glutamine via glutamine synthetase; glutamate synthase replenishes glutamate by transferring an ammonia from glutamine to a-KG as well as reducing a-KG
What do we need to know about glutamine synthetase??
- It is ubiquitous in nature–found in every organism
- It is the primary regulation point in nitrogen metabolism; glutamine is the source of amino in many biosynthetic reactions
- Regulated by 8 allosteric effectors; combined effect of inhibitors AMP, tryptophan, carbamoyl phosphate, CTP, histidine, and glucosamine 6-phosphate are more than additive (synergistic); Gln Synthetase is also regulated by the covalent modification of adenylylation (addition of an AMP)–this inhibits the enzyme and makes it more sensitive to inhibitors; glycine and alanine can also act upon Gln Synthetase to inhibit it
Where does adenylation occur on Gln Synthetase?
Tyrosine residue; ATP is added, and a pyrophosphate is removed
What is the structure of Gln Synthetase?
12 identical subunits, each with a tyrosine for possible adneylylation; the more sites adenylylated means the more sensitive the enzyme is to inhibition
What are the important reactions in amino acid and nucleotide synthesis?
- Transamination reaction via aminotransferase (with coenzyme pyridoxal phosphate, or vitamin b6);
- 1-carbon transfer reactions–enzyme cofactors S-adenosyl methionine (SAM) or tetrahydrofolate aka folic acid vitamin B9);
- transfer of an amino or amide group from glutamine via enzyme glutamine amidotransferase
What does SAM transfer?
One methyl group from methionine
What pathways are all amino acids synthesized from?
Glycolytic, pentose phosphate pathway, and TCA cycle
Remember that amino acids are not always present in equal amounts; they must be synthesized in the correct amounts and the right time for protein synthesis
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What are the non-essential amino acids we need to know?
alanine, aspartate, and asparagine
What are the essential amino acids we need to know?
isoleucine, valine, leucine
What are the types of feedback inhibition?
Product inhibition; sequential inhibition; concerted; and enzyme multiplicity
