MMD Quiz 4/Test 2 (Lectures 6-8)

The structure of an amino acid includes

Amino group

Carboxyl group

Side chain

What part of the amino acid is used in gluconeogenesis?

the carbon skeleton

What happened to the N terminus?

The amino group is transferred to make new amino acids

It is removed from circulation

What is transamination?

The N terminal group from one amino acid can be transferred (forming other amino acids) are formed

Transamination requires specific _________ and can be done on ____ /20 amino acids

enzymes

17/20

What amino acids can NOT be used in transamination?

Serine

Threonine

Lysine

(THREe Serious Liars)

What amino acids usually undergo transamination?

Glutamate (usually in liver)

Alanine (usually in muscle)

For transamination to occur the amino group has to be transferred to a waiting_______

ketoacid

What does the ketoacid become once it is transaminated?

An amino acid

What does the amino acid become when it loses its amino group?

It becomes a ketoacid

Glutamate and alpha KG are considered

amino acid: alpha ketoacid pairs

What can the amino groups be used for?

Make new amino acids or shuttle ammonia around for eventual elimination from the body

Glutamate becomes aminated to become _______

glutamine

What enzyme catalyzes production of glutamine from glutamate?

Glutamine synthetase

Where is glutamine synthetase found?

Liver, CNS, kidneys

What happens when glutamate loses its amino group?

It becomes alpha ketoglutarate

Transaminations can be used to _______ amino acids

synthesize or degrade

Transaminations are catalyzed by a group of enzymes known as ______

transaminases or aminotransferase

What cofactor is required for transamination requirements?

Pyridoxal phosphate (PLP) (derived from Vit B6)

Pyridoxal phosphate is derived from _______

Vitamin B6

Oxidative deamination of glutamate will produce ______

Alpha KG

NADH

NH4+

Via glutamate dehydrogenase

Usually the alpha ketoacid is

alpha kg (usual alpha ketoacid)

How do serine, lysine, threonine release their ammonium ions?

Directly via dehydratases (enzymes) PLP required

Glutamate may go on to be

substrate in generating new AAs

Go be degraded and lose its amino groups in urea cycle

Glutamate is the

main carrier of amino groups or transaminations

Glutaminase converts _______

Glutamine into glutamate

In the fed state, glutamate will

shuttle the amino groups into biosynthetic pathways to generate amino acids

(CREATE NEW AMINO ACIDS = ANABOLIC)

In the starvation state glutamate can

rid itself of ammonia to reform alpha KG to be used in the TCA

Ammonia will then be eliminated via urea cycle

(PROTEIN BREAKDOWN FOR FUEL)

What is another source of ammonia?

The microflora, this is transported to the liver via the portal vein

Alpha KG can scavenge free ammonia to produce _________ via _______ enzyme

Glutamate + NADP+

Dehydrogenase

The reaction of glutamate —> alpha KG +NH4+ (VIA GDH) is an important _____

anapleurotic process (it provides a carbon source for energy production and NADH prod in TCA cycle)

GTP and ATP are ____ allosteric effectors of the formation of glutamate

Positive

(High energy state in the cell favors production of protein)

GDP and ADP are ____ allosteric effectors of the formation of alpha ketoglutarate + NH4+

Positive

(Low energy cell state favors production of A-KG—> you need energy and that feeds TCA)

When the cell ATP level is high there is _______

Decreased conversion of glutamate to alpha KG (and NADP+) and TCA intermediates

When the cell ATP level is low there is a ________

Increased conversion of glutamate to ammonia and oxidizable TCA cycle intermediates

The alpha keto acid of alanine is

pyruvate

The intermediate formed in the conversion of glutamate to glutamine via glutamine sythetase is

gamma glutamyl phosphate

Receives phosphate from ATP

Gamma glutamyl phosphate is converted to glutamine by glutamine synthetase when

An ammonia group displaces the phosphate

_________ is the major transported form of ammonia between the tissues and organs

Glutamine

Why can glutamate not travel to the organs for urea cycle activity?

It is charged

Glutamine is neutral so it can more readily pass through cell membranes

Where does glutamine deliver the ammonia?

Liver

Kidneys

Intestine

In the liver, intestine and kidney, glutamine will

release one mole of ammonia, reforming glutamate in the process (Via glutaminase)

In the liver or intestine, the newly liberated ammonia ion will then

join with bicarbonate to enter the urea cycle

In the kidney, the newly liberated ammonia ion will then

join with H+ to form an ammonium ion that is excreted in the urine directly

Once glutamate is reformed after the first ammonia is removed what may occur?

Oxidized further —> alpha KG for TCA or for more ammonia binding

What is a key difference in ammonia handling between kidney and liver?

Liver uses Bicarb!!

Kidney uses H+ ion to form ammonium which gets excreted into liver

During times of acidosis what happens?

Liver tries to conserve bicarb —> diverts glutamine to the kidney for processing —> ammonia is eliminated without the use of bicarb—> restore body pH

Oxaloacetate is the alpha keto acid of

Aspartate

(conversion via AST)

What is the skeletal muscle transporter of choice?

Alanine

During starvation in skeletal muscle, the amino groups of amino acids will transaminate alpha KG —> Glutamate —> glutamine will then particpate with another transamination reaction:

Pyruvate —> alanine

Alanine xports the ammonia to liver

Once in the liver, what will alanine do?

Transaminate a alpha KG to reform glutamate, generating pyruvate in the process

This pyruvate is then used to make new glucose and deliered back to the blood stream to relieve the starvation state

In the starvation state, will glutamine, alanine, or both be elevated or decreased?

Both will be elevated

Only about _____ of the ammonia is eliminated by the kidney directly excreting ammonium ions. The rest is lost through ____

20%

Urea cycle

In the urea cycle there is the conversion of ammonia to urea, what amino groups does urea contain?

Aspartate and glutamate

What is the rate limiting enzyme of the Urea cycle?

Carbamoyl Phosphate synthetase 1

Ammonia and bicarbonate react to form

Carbamoyl phosphate (requires ATP)

Catalyzed by carbamoyl phosphate synthetase I

Carbamoyl phosphate combines with _________ to form _______ via ornithine transcarbamoylase

ornithine

citrulline

Carbamoyl phosphate combines with ornithine to form citrulline via _________

ornithine transcarbamoylase

Where does the urea cycle occur in?

Liver (mitochondria —> cytoplasm)

Wherre does carbamoyl phosphate synthetase I and ornithine transcarbamylase occur?

The mitochondrial matrix

Citrulline will then _________ and enter the ____

exit the mitochondrial matrix

Cytosol

Citrulline combines with aspartate catalyzed by arginosuccinate synthetase to form

arginosuccinate

Citrulline combines with aspartate catalyzed by

arginosuccinate synthetase to form arginosuccinate

_______ is cleaved off arginosuccinate to form ______— via argininosuccinase

Fumarate

Arginine

Fumarate is cleaved off arginosuccinate to form arginine— via

argininosuccinase

The arginine has the urea at the end of its R group, this is then _______

hydrolyzed off by arginase

Reforming ornithine

Fumarate is used to regenerate ______ by ______

aspartate

entering TCA cycle to form malate —> OAA

Aspartate transaminase

OAA ←→ Aspartate

Carbonic anhydrase is responsible for

the generation of bicarbonate from CO2

A total lack of any urea cycle enzyme is lethal shortly after birth due to

Nitrogen toxicity

Partial urea enzyme deficiencies are called

Urea cycle disorders

Physiological features characteristic of UCD’s (Urea cycle disorder) include

elevations in glutamine and blood ammonia levels

Clinical features of UCDs include (Urea cycle disorder)

encephalopathy, confusion, and cerebral edema (Inc ICP)

What is the main excitatory neurotransmitter of the brain?

Glutamate

(Glutamergic neurons)

What is the glutamate-glutamine cycle?

There is an interaction between cerebral BF, neurons, and protective astrocytes that regulate the metabolism of glutamate, glutamine, and ammonia

Excessive excitation of glutamergic neurons (excess glutamate in the synapse) assoc with

pathophys of stroke and epilepsy

How is glutamate removed from synapse?

Uptake into postsynaptic cell (mod effect)

Synaptic glutamate undergoes reuptake into the presynaptic cell which it was released (greater effect)

Synaptic glutamate is taken up by a third nonneuronal cell known as astrocytes (greatest effect)

What method of glutamate removal from the synapse has the greatest effect?

Synaptic glutamate is taken up by a third nonneuronal cell known as astrocytes

Once the astrocyte takes up glutamate what happens?

Converted back to glutamine which can be held in the astrocyte as a reservoir or be shuttled back to the neuron for reconversion to glutamate

Each time this happens we have one complete glutamate-glutamine cycle occurence

What is the neuroactive version of glut(amine/amate)?

Glutamate is active

Glutamine is not

Glutamine contains

two amino groups

Glutamate contains

one amino group

Inside the astrocyte

glutamate —> glutamine via glutamine synthetase where glutamine is sent back to neurons to reform glutamate

Inside the glutamergic neurons the conversion of glutamine to glutamate is

dependent on the action of phosphate dependent glutaminase (PAG)

Hydrolysis of ATP

During brain depo there is a sudden inc in energy consumption so the shift of ATP to ADP yields a __

Increase in the hydrolysis of glutamine —> glutamate

Fates of brain glutamate include

Use as a neurotransmitter or is deaminated by GDH to form Alpha KG (TCA cycle)

Why is nitrogen so toxic in the brain?

Ammonia will readily cross BBB which is then converted to glutamate from alpha KG via glutamate DH which DEPLETES alpha KG

Disrupting TCA cycle in brain

Damage to cells and neural tissue and cell death

Increased levels of glutamate in response to toxic amounts of nitrogen in the brain will result in _____

depletion of glutamate bc inc —> glutamine

What other neurotransmitter is glutamate a precursor for?

Gamma aminobutyrate (GABBA)

Inhibitory

So, in summary, reductions in brain glutamate (bc of in —> glutamine) will then ____

affect energy production as well as neurotransmission

Another dangerous effect of high ammonia levels results in astrocytes having a high glutamine level will cause ______

cerebral edema and tissue damage due to the osmolytic action of glutamine

In infants with hyperammonemia

Amino acids that can be produced by transamination of alpha ketoacids are considered

Nonessential

Amino acids that can NOT be produced by transamination of alpha ketoacids are considered

essential

Classifications of amino acids include

Ketogenic

Glucogenic

or KeotGlucogenic

Amino acids that yield pyruvate or another TCA cycle intermediate are considered

Glucogenic

How many amino acids are glucogenic strictly ?

14/20

Which amino acids are considered glucogenic?

Alanine, arginine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, proline, serine, histidine, methionine, threonine, valine

Amino acids that yield acetyl CoA or acetoacetate upon catabolic transamination are considered

ketogenic amino acids

Which amino acids are considered strictly ketogenic?

leucine and lysine

What amino acids are considered ketogenic? (produces acetyl CoA or acetoacetate)

Leucine, lysine

Isoleucine, phenylalanine, tyrosine, tryptophan