Biochem Exam 4

lysine ; leucine

only _ and _ are purely ketogenic AA’s

glucogenic

can be catabolized to

• TCA intermediate

• glucose in gluconeogenesis

ketogenesis

pathway that can be catabolyzed to acetyl-CoA

alanine

one of the most abundant AA in blood

(pyruvate analog, ammonia carrier)

glutamate ; alpha ketoglutarate

If making an AA, the universal donor is _ to generate _

nitrogen

PLP goes through this altered enzyme intermediate to hold onto a _ as a transamination is done.

removing nitrogen

First step of catabllozying AA is …

pyruvate ; glutamate

PLP

Alanine becomes _ by giving up it's nitrogen to alpha ketoglutarate to make _.

Using _ cofactor

k

Draw the rxn catalyzed by Carbamoyl Phosphate I

First one was to make bicarbonate attackable, then second phosphate is actual donor.

In rxn catalyzed by Carbamoyl Phosphate I

Only one phosphate on the product, why did it use 2 (ATPs)?

1. Ornithine transcarbamylase

2. Argininosuccinate synthetase

3. Argininosuccinase

4. Arginase

Urea Cycle 4 Enzymes:

Don’t draw any reactions, but recognize/be able to put in order

Ornithine transcarbamylase

_ is the only Urea Cycle reaction in the mitochondria

Lysine

Ornithine is _ with one less carbon

Argininosuccinate synthetase

What adenylates citrulline to allow attack from aspartate?

Argininosuccinate

in urea cycle,

the big molecule u dont wanna memorize

(citrulline + aspartate)

citrullyl-AMP intermediate

urea cycle intermediate between citrulline and argininosuccinate?

bicarbonate in CPS 1

Where did yellow carbon come from?

inorganic ammonia in CPS 1

Where did blue N come from?

aspartate

Where did green N come from?

Argininosuccinase

In the urea cycle,

What breaks down argininosuccinate, generating arginine and releasing fumarate?

Arginase

In the urea cycle,

What breaks down arginine, generating urea and regenerating ornithine?

AA

no storage for _s

acetyl-CoA + glutamate → CoASH + N-acetylglutamate

_{NAG is like a “go” signal: its presence tells the liver, “There’s enough substrate (glutamate and acetyl-CoA) and nitrogen to start the urea cycle.”}

_{CPS1 is inactive without NAG.}

N-acetyl glutamate synthase (NAGS) reaction?

N-acetylglutamate

is an essential and obligatory allosteric regulator of CPSI

arginine

N-acetylglutamate is activated by _

• Glutaminase, Glutamate by oxidative deamination

• Aminotransferase using PLP cofactor

• Bicarbonate

• hydrate and then oxidize
  (fumarate —> malate —> OAA —> aspartate)

Overall Urea Cycle Reaction

• Where did the green ammonia come from (if in the Liver)?

• The red one?

• Carbon in urea came from?

• How can fumarate be converted back into aspartate (step by step)?

• Glutamate

• Alphaketoglutarate

• What alpha AA is this?

• What’s the alpha keto acid?

yea :(

got it?

• glutamate

• pyridoxal phosphate (PLP)

How amino groups are collected: transamination

• The −NH₂ on most amino acids is moved to α-ketoglutarate → _; the original amino acid becomes its α-keto acid (its carbon skeleton).

• Enzyme/cofactor: aminotransferases (a.k.a. transaminases) use _, which forms a Schiff base with the amino acid and stabilizes carbanion intermediates (acts as an “electron sink”). generally reversible

This funnels many different amino-nitrogens into a single pool (glutamate), which is then processed to release ammonia or to carry nitrogen between tissues.

glutamate

universal nitrogen carrier

alpha-ketoglutarate

universal nitrogen acceptor

Glutamate dehydrogenase (GDH)

_ in mitochondria of liver catalyzes oxidative deamination:

glutamate → α-ketoglutarate + NH₄⁺.

ADP ; GTP

GDH can use NAD⁺ or NADP⁺ (in mammals both work).

It’s allosterically regulated (activated by _, inhibited by _): the cell links nitrogen removal to energy status.

transamination

_ interconverts an AA and a α-ketoacid

oxidative deamination

_ of glutamate releases ammonia for disposal

run backwards with alpha-KG as the acceptor and glutamate as product

How is PLP regenerated to restore enzyme?

glutaminase

^{(Glutamine Amidotransferase: a complex of at least 2 subunits:
a glutaminase and a synthase.)}

_ will remove the nitrogen on glutamine —> glutamate

fine

Draw Glutamate DH reaction

Carbamoyl phosphate synthetase I (CPS1)

_ is an enzyme in the mitochondria that catalyzes the first step of the urea cycle, converting ammonia and bicarbonate into carbamoyl phosphate.

_{draw entire reaction}

(ammonia recaptured via) synthesis of carbamoyl phosphate

First nitrogen-acquiring reaction of urea cycle …

• Ornithine transcarbamoylase

• Argininosuccinate synthetase

• Argininosuccinase

• Arginase

Nitrogen from carbamoyl phosphate enters urea cycle.

• Enzyme 1: _ , only rxn in mitochondria

• Enzyme 2: _ , adenylates citrulline to allow attack from Asp

• Enzyme 3: _, generates Arg, releases fumarate

• Enzyme 4: _, generates urea, regnerates ornithine

entry of aspartate (into urea cycle)

second nitrogen-acquiring reaction in urea cycle?

• ala

• asn

• asp

• glu

• ser

Nonessential AA’s?

• H, I

• Leu, Lys

• M, P

• Thr, Trp

• V

essential AA’s?

alanine

pyruvate precursor?

• glutamate

• glutamine

• proline

• arginine

α-Ketoglutarate precursors?

• serine

• glycine

• cysteine

3-phosphoglycerate precursors?

• aspartate

• asparagine

Oxaloacetate precursors?

starving / bad diet

(insufficient AAs)

negative nitrogen balance indicative of?

growth (excess dietary AAs)

positive nitrogen balance indicate of?

acetoacetate

Leucine and Lysine are precursors of …

aspartate (via urea cycle)

fumarate precursor?

α-KG —> glutamate —> proline or arg (via urea cycle!!)

How are Pro and Arg derived from Glutamate?

Draw glutamate to proline (no int steps)

Glu

… from _

MEMORIZE PIC

ok

Draw Asn from Asp from OAA!

and backwards!

inorganic ammonia

N source of glutamine?

glutamine

N source of asparagine?

3-PG of glycolysis

serine derives from …

Homocysteine and Serine (in mammals)

Cysteine derives from _ + _

• Folate is versatile but not potent/powerful

• SAM is not versatile (only transfers methyls) but is very strong

Folate vs SAM?

folate

_ can transfer a carbon in many oxidation states (methyl, methylene, formal-), but is not a good transferase.

it’s a 1-C carrier

N5-methyl THF

Reduction of:
N5,N10-methylene THF —> ____

is irreversible

methionine synthase

N5-methyltetrahydrofolate can only be used by which enzyme?

Met. Synth. can only make methionine out of methionine

(While methionine synthase can convert homocysteine back to methionine, this conversion relies on other nutrients like folate and vitamin B12, and it's the overall balance of incoming dietary methionine and its subsequent use that determines nutritional status.)

Why is methionine an essential amino acid if Methionine Synthase is an enzyme that makes methionine in the body?!

homocysteine ; N5 THF

B12

Methionine Synthase requires _, _,

and _ (MOST IMPORTANT)

Homocysteine

_ is derived from methionine but is also required for Methionine production

B12

Lot of folate in diet/body, but N5 accumulates?
Deficiency in _, leading to failure to convert to Met and produce THF

1. B12-dependent methionine synthase

2. Cysteine synthesis pathway

When homocysteine levels are high, 2 pathways to rid of?

Methionine

(which came from homocysteine, which came from SAM)

Where did cysteine’s sulfur come from?

Methylmalonyl-CoA mutase

Methionine synthase enzyme requires B12. What other enzyme requires B12?

• Clears odd chain FAs
  (methylmalonyl-CoA —> Succinyl-CoA)

• if no B12, buildup —> toxic

• What does methylmalonyl-CoA mutase do?

• Why would it build up?

dehydrogenase

Look at all these _ complexes!

irreversible reduction

5,10methylene-THF —> 5-methyl-THF is _

Folate ; Methionine

_ and _ cycle summary

tyrosine hydroxylase

RLS enzyme of dopamine production?

uses iron intermediate

dopamine

_ is a precursor for norepinephrine and epinephrine

catechol

this is a _ group

L-DOPA

precursor for dopamine called?

biopterin

_ is a cofactor for aromatic AA hydroxylase enzymes

ascorbate

Vitamin C = ?

phenylalanine hydroxylase

fill in blank

PKU

phenylalanine hydroxylase deficiency —> ?

tyramine

decarboxylase tyrosine to get _

biopterin and iron

2 cofactors of tyrosine hydroxylase?

aromatic L amino acid decarboxylase (AADC)

L-DOPA —> dopamine by what enzyme?

serotonin

who dis?

tryptophan

who dis?

PLP

cofactor for transaminations and decarboxylations?

monoamine oxidase

enzyme in first step of oxidative deamination?

FAD required, H₂O₂ produced

inhibitory

GABA is a _ NT

stimulatory

Glutamate is a _ NT

decarboxylation

histidine to histamine is a _

oki

Draw Trp to Serotonin!

MAOI

after serotonin reuptake, can be destroyed by _ --> blood --> kidneys --> urine

monoamine oxidase

_ turns dopamine amine into a carboxylic acid (DOPAC)

increase

blocking MAO with MAOI can _ monoamines

dopamine

norepinephrine

serotonin

name the three monoamines

VGLUT

(vesicular glutamate)

Eat glutamate from diet, use as NT, pack into vesicle using _.

Then depolarization occurs, Ca²⁺ release triggers exocytosis of NTs.

kainate, AMPA, NMDA

glutamate receptors (3) …