BB451 Nitrogen Metabolism

NITROGEN METABOLISM

What chemical denotes atmospheric nitrogen?

N2

Which organisms can turn nitrogen into a usable form? Which cannot?

Bacteria can (through nitrogen fixation). most plants and animals can't

Can you name some cellular molecules made with nitrogen?

amino acids and nucleotides

Can we use atmospheric nitrogen to make these?

NO 

What is the nitrogen cycle?

the series of processes by which nitrogen and its compounds are interconverted in the environment and in living organisms, including nitrogen fixation and decomposition.

What is transamination?

the transfer of an amino group from one molecule to another

What are some non-protein amino acids?

Ornithine

Citrulline

Sacrosine

How is nitrogen excreted? (Several molecules.)

ammonia-fish

Uric acid-birds

urea- most vertebrates and some in invertebrates (smallest, only 2 nitrogen)

Why do you check the pH of your fish tank frequently?

ammonia levels can build up.

How do we humans excrete excess nitrogen?

urea (primary) but also uric acid

How is the glucose-alanine cycle like the Cori Cycle?

both cycles involve the transport of a metabolic byproduct from muscle tissue to the liver, where it is converted back into glucose to be used for energy, except that muscle pyruvate is converted to the amino acid alanine rather than lactate by transamination in the glutamate–pyruvate transamination reaction.

How is glutamate (glutamic acid) central in nitrogen metabolism?

it acts as a primary acceptor of amino groups from other amino acids through transamination reactions, effectively serving as a key "hub" for transferring nitrogen within the body, allowing for the synthesis of other amino acids and the detoxification of ammonia; it is also readily converted to glutamine, which can transport nitrogen to other tissues where it is needed. All products are important to cells.

What is the urea cycle? Where does it occur in the cell? In the body?

• Primarily occurs in liver & kidney (partly in mitochondria, partly in cytoplasm)

• Consists of 4 cycle reactions and 1 feeder reaction

• The net reaction per turn of the cycle is

2 NH 3 + CO 2 + 3 ATP + H2O → urea + 2 ADP + 4 Pi + AMP

(taking 2 ammonia and converting to urea using CO2, energy, and water)

When free ammonium ions are picked up, what is it combined with?

bicarbonate, makes carbamoyl phosphate

What is made next?

carbamoyl phosphate and Ornithine combine to form citrulline

Now what can happen to those products? 

citrulline is transported out of the mitochondria via an antiport that takes in ornithine, then reacts with aspartic acid

What does the enzyme arginase do and why would it act? Or why might it not?

cleaves arginine to make urea and ornithine. would act or not depending on if arginine is needed to make proteins 

If I told you that Orange Colored Cats Always Ask For Awesome Umbrellas, what is this a mnemonic for?

Orange-Ornithine

Colored-Carbamoyl Phosphate

Cats-Citrulline

Always-Aspartate (enters the cycle)

Ask-Argininosuccinate

For-Fumarate (leaves the cycle)

Awesome -Arginine

Umbrellas-Urea (leaves the cycle)

What else do cells use citrulline for?

produces nitric oxide, which is used for cell signaling (vasodilation)

What are two ways citrulline is made?

1. As a byproduct of the urea cycle, 

2. through the breakdown of arginine by the nitric oxide synthase (NOS) enzyme 

What amino acids are in the glutamate family? 

glutamate, arginine, glutamine, proline

What do they derive from?

a-ketoglutarate

Why is their synthesis carefully regulated?

because they are starting materials for a lot of amino acids

What amino acids are in the serine family 

serine, cysteine, glycine, selenocystine

What do they derive from?

3-phosphoglycerate

How does cysteine get its sulfhydryl group?

from methionine

How does serine easily become glycine?

removal of CH2OH group (gets donated to folate)

What about vice versa? What else is needed?

Folate with CH2OH group can give it back

What is special about selenocysteine?

contains selenium, is encoded by stop codon (unique mechanism for incorporation into proteins)

What enzyme that we learned about recently uses selenocysteine?

thioredoxin reductase

What amino acids are in the aspartate family?

made from oxaloacetate

aspartate, asparagine, Lysine, threonine, methionine, 

What amino acids are in the aromatic family?

Tryptophan, phenylalanine, tyrosine

What medically relevant molecules do you recognize that are made from this family?

melatonin, serotonin, thyroid hormones, melanin

What does tryptophan give rise to? Do you recognize these molecules and what they do?

melatonin, serotonin, Niacin (B3, Nicotinamide is derived from it), Auxins (stimulates cell ÷) 

What sugar replacement is made with phenylalanine?

Nutrasweet (aspartame) really bad for people with PKU (high levels result in brain damage)

What is the disease PKU

Deficiency  of the phenylalanine hydroxylase enzyme (phenylalanine builds up)

What molecules are made from tyrosine?

Catecholamines (NT): Dopamine, epinephrine/norepinephrine

How is tyrosine therefore relevant to Parkinson’s Disease?

PD= problems with dopamine synthesis. treated with L-Dopa (dopamine precursor)

Where do thyroid hormones derive? 

tyrosine, contains iodine

How is tyrosine relevant to melanin?

melanin is oxidized and polymerized tyrosine. more polymerization=more absorption=darker color

What amino acids are in the pyruvate family?

alanine, leucine, isoleucine,valine

Which are the branched-chain amino acids?

valine, leucine, and isoleucine

What is maple syrup urine disease?

not being able to metabolize branched-chain amino acids

What amino acid is in the histidine family?

histidine

What is notable about how it is made?

Made from ribose-5-phosphate (also uses PRPP)