nitrogen metabolism

what are amino acids used in (4 things)

protein synthesis

synthesis of important nitrogenous compounds

use of carbon skeletons for fuel in TCA cycle

use of carbon skeletons to make glucose and ketone bodies

use of carbon skeleton requires

excretion of amino nitrogen

(cuz you want the carbon group not the nitrogen group)

the more important fate of amino acids (by mass)

generation of carbon skeletons and N-containing compounds

this is more important than protein synthesis

essential amino acids that cannot be synthesized by humans

MTW HF LIV (R)K

M - methionine

T - threonine

W - tryptophan

H- histidine

F - phenylalanine

L - lysine

I - isoleucine

V - valine

R - arginine

K - lysine

is arginine essential

to develop embryo and fetus but we can synthesize it as adults

so only for embryo and fetus

nonessential amino acids that we can make from glucose

serine

glycine

cysteine

alanine

aspartate

asparagine

glutamate

glutamine

proline

arginine

basically all the others except tyrosine

nonessential amino acid that we make from an essential amino acid

what amino acid makes it

tyrosine

comes from phenylalanine

carbons of cysteine come from ___ but the sulfur comes from ____

glucose

methionine

some plant proteins are deficient in

how to remedy this

amino acids

complement one source of plant protein with another

legumes lack

methionine

grains lack

lysine

beans and rice together (legumes and grains) provide

all the essential amino acids

soybeans are equivalent to _____ in terms of digestible protein value

but they have low ____ content

eggs

low methionine content

every amino acid except lysine (K) and leucine (L) are

which means what

glucogenic

their carbon skeletons contribute to making glucose with gluconeogenesis --> they can be metabolized to pyruvate or TCA cycle intermediate

strictly ketogenic amino acids

lysine and leucine

which amino acids can do both

form ketone bodies and glucogenic

tryptophan

isoleucine

threonine

tyrosine

phenylalanine

WITY F

(wity fugger)

main precursors of gluconeogenesis (4)

this makes up ____ percent

lactate

alanine // glutamine in kidney

glycerol (converts to DHAP through F6P)

90%

"LAG"

main precursor for gluconeogenesis in kidney

glutamine (not alanine)

the other 10% of precursors for gluconeogenesis

other amino acids get metabolized to TCA cycle intermediates

which eventually become oxaloacetate

How does oxaloacetate get to location needed for gluconeogenesis

malate transports it to the cytosol

to generate PEP

what do lysine and leucine get metabolized to

acetyl coA

(not pyruvate or TCA intermediates)

2 long term storage forms of energy in the body

protein and fat

fatty acids only produce ___ they cannot make ___

acetyl coA

glucose (glycerol can)

amino acids make blood glucose during ___

fasting state (12+ hours)

skeletal muscle starts getting degraded to make glucose

the excess ammonium produced when amino acids make glucose during fast gets converted to

urea

when blood glucose is low

acetyl coA in the liver is used to form

(so this is what leucine and lysine and some others make)

acetoacetate and beta-hydroxybutyrate

these are ketone bodies

carbons from acetyl CoA get released as ____ in the TCA cycle

co2

can animals form new glucose from co2 (that is released from TCA)

no

only plants and some prokaryotes can

acid in the stomach

HCl

endoprotease vs exoprotease

cut protein inside the peptide chain

cut from the ends of the chain (N or C terminus)

pepsin

key role

location

cleaves after

endoprotease

FIRST protease

in stomach

Phe, Tyr, Glu, Asp

(F, Y, E, D)

zyomgen of pepsin

how it gets activated

pepsinogen

by acid (H+), by pepsin

trypsin

key role

location

cleaves after

endoprotease

ACTIVATES OTHER ZYMOGENS

intestine

Lys, Arg

(its a basic bish)

zyomgen of trypsin

how it gets activated

trypsinogen

enterokinase

(enteropeptidase)

proteases are born as

zymogens (proenzymes)

3 zymogens trypsin activates

chymotrypsinogen --> chymotrypsin

proelastase --> elastase

procarboxypeptidase --> carboxypeptidases

amino acid transport in the intestinal lumen brush border, gut, and kidney

what proteins do it

specificity is ___

5 specificity groups are

sodium linked carriers

broad specificity

1) system A

2) N

3) X-AG

4) ASC

5) y+L

4 nitrogenous urinary excretory products

(disposed nitrogen to use carbon skeleton)

urea

NH4+

creatinine

uric acid

aminotransferase reactions (transamination) are when

give example

the amino group is transferred

AA1 <--> aKetoacid1

aKetoacid2 <--> AA2

example:

aspartate <-> oxaloacetate

a-ketoglutarate <-> glutamate

what is the cofactor used in aminotransferase reactions

PLP = pyridoxal phosphate (vitamin B6)

what is the universal receiver of amine groups

a-keto acids

(a-ketoglutarate)

characteristics of aminotransferases (3)

freely reversible (the amino can go both ways)

AT for all amino acids

most use glutamate/alpha-ketoglutarate as one pair (glu is the gathering point)

glutamate dehydrogenase reaction

what becomes what

what is used

what is released

Glutamate <-->

α-Ketoglutarate

uses NADP+

releases NADPH and ammonium

Ammonium is ________

how to prevent its accumulation

toxic

UREA CYCLE (makes it less toxic)

key precursors of urea cycle

amino acids (glutamate, aspartate)

a-ketoglutarate from transamination rxns

ammonium (NH4+)

other reactions

3 places ammonium comes from to enter the urea cycle

1. alanine conversion to pyruvate (gluconeogenesis generates NH4)

2. glutamate dehydrogenase (this one makes free ammonium)

3. aspartate formed by amination of oxaloacetate

AGA

amination of oxaloacetate makes

aspartate

N-acetyl glutamate

made up of what 2 things

activated by what

activates what

significance of it

glutamate + acetyl coA

activated by Arginine

it activates CPS-1 which drives the urea cycle

so it is the key enzyme and regulator of the urea cycle

why does arginine activate NAG synthesis

arginine excess means excess of ammonia

so turns on NAG to start urea cycle

what does carbamoyl phosphate synthetase (CPSI) catalyze

turns co2 + ammonium

into

carbamoyl phosphate

these 2 enzymes collaborate to send nitrogen into urea cycle

aminotransferases

glutamate dehydrogenase

urea production increases during

fasting

muscle starts using protein and makes free alanine which becomes pyruvate to make glucose and ammonium in the liver

so that ammonium goes into urea cycle

humans can synthesize carbon skeletons of many amino acids from __

glucose

(the glucogenic ones)

(this leads to free toxic ammonium)

what are the things you need to make NONESSENTIAL amino acids

(3 main things and one enzyme)

glucose

methionine (for sulfur in cysteine)

phenylalanine (for tyrosine)

transaminases

serine synthesized from

3-phosphoglycerate

(3 PG)

2 enzymes that turns

3-phosphoglycerate into serine

serine inhibits this (feedback inhibition)

3-phosphoglycerate dehydrogenase

(3PG DH)

phosphoserine phosphatase

glycine synthesized from (2 things)

mostly from

serine or threonine

mostly serine

proline is synthesized from

glutamate semialdehyde

glutamate gets reduced to it

ornithine synthesized from

glutamate semialdehyde

glutamate semialdehyde is a direct precursor for (2 things)

proline

ornithine

arginine is synthesized from ___

in the ____ cycle

ornithine

becomes Arg in the urea cycle

Cori Cycle analog uses

branched chain amino acids

shuffles them from muscle to liver

branched chain amino acids get ____

where does this happen

where does it not happen

deaminated and metabolized

(for carbon skeleton)

in the muscle and brain

they do NOT get oxidized in the liver

3 branched amino acis

valine

isoleucine

leucine

first 2 steps of metabolism of branched amino acids

1. aminotransferase

2. decarboxylating dehydrogenase

3. stuff happens and then final fates

maple syrup urine disease

defective in

presents after

causes accumulation of

a-keto acid dehydrogenase

after first protein meal - it's a amino acid metabolism disorder

branched chain alpha keto-acids

symptoms of maple syrup urine disease

failure to thrive

feeding difficulties

developmental delay

convulsions

why is it called maple syrup urine disease

sweet odor of branched chain alpha keto acids + byproducts

(sweet urine)

single carbon pool aka __

synthesizes __ and __

folate cycle

synthesis of neurotransmitters and nucleotides depends on this

sources of one carbon units in the folate cycle

serine

glycine

histidine

formaldehyde

formate

tryptophan?

H G S, F F

the one carbon pool in folate cycle includes (3)

THIS IS HOW THE ONE CARBONS CAN EXIST

carried by a ___

formyl <->

methylene <->

methyl

carried by FH4 (tetrahydrofolate)

products of folate cycle/single carbon pool (4)

dTMP

serine

purines

B12 - methyl

what happens in the absence of folate in blood

megaloblastic anemia

because failure of blood cell precursors to make final division

key role of folate

which is needed to

nucleotide synthesis

replicate DNA

low folate in first weeks of pregnancy cause

neural tube defects

--> spina bifida

sources of folate (3)

leafy green veggies (foliage)

orange juice

its required in flour now

nutritional folate gets reduced to ___ inside of us

what enzyme does this

FH4 = tetrahydrofolate

(this is the one that can carry a carbon in the pool)

dihydrofolate reductase (does it twice and releases 2 NAP+)

FH4 carries single carbons in a variety of

list the path

oxidation states

FH4 becomes:

N10-formyl-FH4

N5,N10-methenyl FH4

N5,N10-methylene-FH4

N5-Methyl-FH4

THE LAST STEP GOING FROM METHYLENE FH4 TO METHYL IS NOT REVERSIBLE

primary donor of single carbons

what do they feed into

more abundant than

serine and glycine

feed into N5 N10 METHYLENE FH4

they are more abundant than histidine and tryptophan

(histidine feeds into n5n10 methenyl

tryptophan feeds into n10 formyl)

what is the major acceptor of methyl groups from folate

how does this happen

what does this generate

vitamine B12

methylene gets reduced to methyl which goes to B12

methionine from homocysteine methylase

without vitamin B12 folate will get trapped in this form

methylated form

not enough folate leads to _____

not enough vitamin B12 leads to _____

anemia

ALSO anemia (folate gets TRAPPED SO THERE IS LACK OF FOLATE)

vitamin B12 is required by (2 enzymes of 2 reactions)

methylmalonyl coA mutase

homocysteine methylase

B12 deficiency causes a buildup of _______ (2 reactions its in)

what do these cause

buildup of homocysteine (methionine)

causes heart disease

buildup of methylmalonate (MMCoA)

causes demyelination

what is needed to absorb B12

INTRINSIC FACTOR in stomach

pernicious anemia

treatment

cells that secrete intrinsic factor get destroyed in autoantibodies

B12 injections or sublingual B12 (bloodstream)

other enzymes/factors needed in methionine metabolism to become glucose

folate

B12

SAM

PLP (B6)

SAM 's relationship to methionine

required metabolite of methionine

a methyl group donor

enzyme used in NON-B12 DEPENDENT METABOLISM OF HOMOCYSTEINE

deficiency in this can cause

symptoms

treatment

beta-synthase (CBS)

causes accumulation of homocysteine in blood/urine and increased risk of cardiovascular disease

lens dislocation, pectus excavatum, heart attack

treat with multivitamin (B6) or B12 to increase other path to metabolize it

uses of SAM

norepi --> epi

guanidinoacetate --> creatine

nucleotides --> methylated nucleotides

phosphatidylethanolamine --> phosphatidylcholine

acetylserotonin --> melatonin

IT CREATES METHYLATED PRODUCTS

serotonin and melatonin come from

tryptophan

synthesize of serotonin and melatonin

Trp hydroxylase

BH4 (tetrahydrobiopterin)

5HT becomes serotonin OR metabolized by MAO-A

serotonin gets acetylated

then gets methylated by SAM to make melatonin

SSRI's

selective serotonin reuptake inhibitors

enhance serotonin lifetime in depression, ocd, anxiety

prozac, etc.

catecholamines include _____ which come from

dopa, dopamine, NE, epi

come from phenylalinine/tyrosine

synthesis of catecholamines uses these enzymes (4)

phe hydroxylase

tyr hydroxylase

BH4 -- tetrahydrobiopterin

SAM

where does BH4 (tetrahydrobiopterin) come from

GTP

melanin (pigment) comes from

tyrosine

histamine comes from

histidine

histamine mostly made and released in

sometimes made in (2 places)

what does it do in each place

mast cells - inflammation

stomach - regulates H+

brain - regulates sleep/wake in hypothalamus