Neufeld Proten And Aa Synthesis

Front 1

Protein Malnutrition:
Kwashiorkor syndrome
Famine Edema
Protein energy Malnutriton
In US can occur in

Back 1

- protein deficiency but adequate calories
-edema gives puffy appearance

-Inadequate syntehsis of plasma proteins especially albumin.
-Osmotic pressure not maintained and fluid escapes into tissues
-Water in EC space is increased relative to body weight
-lack protein not calories


-Starvation, lacks calories and proteins as well as other nutrients

-pregnant and lactating women
-eating disorders
-elderly, chronic ill
-chronic alcholoics/substance abusers
-hospital patients
-genetic disorders

Front 2

Essential vs. Non essental

Back 2

-Essential = cannot synthesize
-Non essential = can synthesize via TCA

PVT TIM HALL = Essential

Front 3

how much Protein do we need:
compared to fat/glucose?
can we get all from one source?
protein needs for: infants, children, teens, adults, pregnant, athletes kg/kg and g/day

Back 3

no significant storage pool, need to consume daily

proteins differ in contest of essential AAs and digestilbity, need multiple sources

g/kg: Infants(2.2)>children(1.8-1.25)> atheletes(1.7-1.2)>teen(1.0-.8)> adults male and female(.8)[pregnant/lactating needs 20-30% more]

G/day: Adult Male(56)> Teens(45-55)>female(44)> children(38-20)> infants(20-6.5)

Front 4

Nitrogen Balance Flow diagram

Back 4

Dietary Protein-->digest-->aa:
-(translation)endogenous proteins
-other N compounds
-a-ketoacids: glucose, lipids, energy
-NH3: urea-->excretion

Front 5

Nitrogen Balance
In N balance:
Positive N balance:
Negative N balance:

Back 5

excretion = intake

excretion<intake(growth, pregnaancy, tissue repair)

excretion>intake( malnutrition, starvation, illness, surgery, burns)

Front 6

Pro-enzymes, converted by, active enzyme

pepsinogen
trypsinogen
chymotrypsinogen
pro-carboxypeptidases
pro-elastase

Back 6

pepsinogen-->H+ pepsinogen-->pepsin
trypsinogen-->enteropeptidase-->trypsin
chymotrypsinogen-->trypsin-->chymotrypsin
pro-carboxypeptidases-->trypsin-->carboxypeptidase
pro-elastase-->trypsin-->elastase

Front 7

Problem with cystic fibrosis regarding enzymes?

Back 7

-secretion is imparied, need supplement with pill

Front 8

amino Acid absorption in small intestine is dictated by:

#, located, special, requries?

Back 8

6 brush-border enzymes specific for uptake of amino acids, for class of amino acids, requires energy

Front 9

endogenous proteins back to amino acids is called?

used to?
purpose?
major sites of turn over?
turn over time?

Back 9

Protein turnover

-dispose of damaged proteins and allow cells to respond to different conditions

-conserves resource and reduces need to dispote of waste metabolic products

-proteasomes(cytoplasm) and lysosomes

-1/2 lifes of proteins vary

Front 10

Proteolysis in proteasomes process flow chart

where does UBQ bind?

Back 10

Protein + Ubquintin-->ubiquinylated protein
*ATP

ubiquinylated protein-->proteosome-->peptides
*ATP

ubiquitin returned and not degraded


-UBQ's carboxyl terminus forms an isopeptide bond with the E-amino groups of lysine in proteins.

Front 11

Proteasomes:
speed and specifity?
for?
structure(size, units, shapes)?
how are proteins targeted?
UBQ and degradation require?

Back 11

-fast and specific

-proteins of which must be regulated carefully and for damaged/mutant proteins

-large, mutliunited, cylinder shaped witha central capped at both ends

conjugation via Ubiqutin

ATP

Front 12

Proteolysis in Lysosomes:
speed and specifity?
for?
suited for?

Back 12

-slow and non selective

-plasma membrane proteins and extracellular proteins taken in by endocytosis of phagocytosis

-low pH

Front 13

Other proteolytic systems

Back 13

-numberous other proteases in the cell requried for apoptosis(caspases)

Front 14

Biosynthesis of non-essential amino acids

Back 14

-glucose, lipids, energy-->a-ketoacids-->amino acids

Front 15

Transamination
allows for?
catalyzed by?

Back 15

transfer of a NH2 group from an amino acid to a ketoacid to make another amino acid

transaminases

a-amino acid 1 + a-ketoacid 2 --> a ketoacid 1 + a-amino acid 2

Front 16

a co-factor for reactions of amino acids other than transamination, and transaminases

derived from?

conversion proces

Back 16

pyridoxal phosphate

Vitamin B6

pyridoxine(vitamin B6)-->pyridoxamine-->pyridoxal-->pyridoxal phosphate

Front 17

Key players in amino acid metabolism

Back 17

glutamate

a-ketoglutarate

glutamine

Front 18

Fxn of glutamate dehydrogenase rxn?
*

Back 18

converts glutamate into alpha ketolgutarate or a-ketoglutarate back to glutamate

*
enables either the conversion of a-ketoglutarate-->glutatamine by donating at NH3(glutamate-->a-ketoglutarate as a consequence)
*NAD is reduced

or

the reverse glutamine-->a-ketoglutarate by accepting NH3(also converting a-ketoglutarate(glutamate)--> glutamate as a consequence))
*NADPH is oxidized)

Front 19

synthesis of glutamine
need energy?

Back 19

-Glutamate-->glutamine(glutamine synthetase)
*ATP-->ADP, NH3 expended

yes

Front 20

Hydrolysis of Glutamine
need energy?

Back 20

Glutamine--> glutamate
* H20-->NH2, glutaminase)

no

Front 21

Fxn of glutamine

Back 21

-non toxic form of transport and storage of ammonia-->most abundant amino acid in circulation

Front 22

Synthesis of non-essential amino acids and role of pyridoxal phosphate

Back 22

* = pyridoxal phosphate
glycolysis:
glucose-->P-glycerate-->pyruvate:

Phosphoglycerate-*>Serine-->gly/cys<--met
Pyruvate-->ala

From TCA:

fumarate-->malate-->oxaloacetate:
*->Asp-->Asn
+ Acetyl coA-->Citrate-->a-ketoglutarate:

-->succinate-->fumarate-->malate
-*-> Glu-->Gln+ Pro

Front 23

Synthesis of tyrosine:
derived from ____ via ____
cofactor:
biopterin is syn from __ and is thus not a ___

rxn

Back 23

phenylalanine oxidation

tetrahydrobiopterin

GTP, not a vitamine

Phenylalanine-->Tyrosine
* O2-->H20
*tetrahydrobipterin + NADH-->dihydrobiopterin-->NAD
-DHB reductase

- tetrahydrobipterin essentially donates an Hydrogen by forming a double bond

Front 24

Synthesis of Cysteine
2 steps?
rxns require?
which rxns act where?

is homocystein essential?

what is essentially happening

Back 24

1. Condesation of serine with homocysteine-->cystathionine
* cyastathionine snyhtase
PLP lose H20

2. cleavage of cystathionin-->cysteine + a-ketobutyrate

cystathionase, PLP, H20

condesation/cleavage occurs at different sides of the sulfur atom

-no, not found in proteins
-Sulfur group transfered from homocysteine to serine to form cystein

Front 25

Synthesis of cysteine

Back 25

Front 26

Methionine to homocysteine(SAM)?
SAM's fxn?

Back 26

donor of methyl groups in acell, acceptors include DNA, protein, lipids, NTs

Front 27

SAM:
how is methyl group of methionine activated?
what to transfer of methyl to aceptors give rise to?
donates methyl to?

Back 27

linkage to SAM

SAH

norepinphrine-->epinephrine
acetylserotonin-->melatonin
phosphatidylethanolamine-->phosphatidycholline
guanidinoacetate-->creatinine

Front 28

Regulation of methionine
regenerated to via?

Back 28

transfer of methyl from N5-methyltetrahydrofolate(-->tetrahydrofolate) to homocysteine

cofactors: B12, B6(pyridoxal phosphate), folic acid

Front 29

folic acid:
is reduced to?
which plays a role in?

Back 29

-tetrahydrofolate
-carbon transfer rxns for purine and pyrimidine synthesis for AA metabolism

Front 30

Synthesis of thymidine role in cancer
REFERENCE

Back 30

-dihydrofolate reducatase[-- methotrexate+aminopterin(analogs of folate)

- FU --> Fdump irreversibly inhibits thymidylate synthase(suicide substrate)

Front 31

vitamin B12
synthesized? stored?
what rxns?
requires ___ made by ___ for ___ in ___
transport proteins that carry it to the liver are called?

Back 31

bacteria, stored in liver

1. homocysteine-->methionine(folate involved)
2. methylmalonylcoA-->succinylcoA(folate not involved)

intrinsic factors(glycoprotein), gastric parietal cells, absorption, illeum

transcobalamins

Front 32

Folate vs. Vitamin 12

both needed for?
no B12 leads to?
results in?
reintroducing folate can?

Back 32

-Both need for conversion of homocytsteine to methionine

-folate trapped as N5 methyltetrahydydrofolate

-megaoblastic anemia and neuropathy

-correct anemia but not neuropathy

Front 33

folic Acid supplmentation
-deficiency of folic acid can cause what?
-1998:-->?
-too much folic acid?

Back 33

neural tube defects in pregnant women(spina bifida, anencephaly)

1998: mandate spplementation of grain products-->reduction in spina bifida 20%

mask Vitamin B12 deficiency causing neurologic damage

Front 34

Amino Acid Catabolism:

direct sources of ammonia in liver?

Back 34

-NH3 neurotoxic is convered in liver to urea which is non-toxic and soluble-->excreted

-glutamate
-gluatamine: transported form other tissues
-alanine: transported from muscle for gluconeogensis and converted to pyruvate in liver genreating NH3

Front 35

Urea cycle:
takes place?
converts?
enzymes located ?

Back 35

-liver

-converts NH3 to urea

- 2 in MC, 3 in cytosol

Front 36

Urea cycle 3 facts

Back 36

1. important
2. substrates are running around
3. Ornithine is essential and not consumed in the reaction

Front 37

Urea cycle regulation

Back 37

1. transcription high when protein intake is high

2. Control of first enzyme; arginine activates N-acetyl glutamate synthetase allosterically

Front 38

Urea cycle malfxn
occurs when?
most severe?
mildest?
also seen in?

Back 38

genetic disorders alter fxn of any of the enzymes

neonatal hyperammonemic coma, mental retardation, cerebral palsy

episodic hyperammonemia precipitated by high protein intake/infection

malfxn of urea cycle seen in liver failure(non-genetic)

Front 39

Malfxn of Urea cycle leads to?

2 hypothesis

Back 39

accumulation of ammonia in plasma and tissues(including brain) --> vomiting siezers, somnolence, coma and death

1. Toxicity of glutamine: high levels accumulate in astrocytes which have potent gluatmine synthesate leads to osmotic pressure(swelling and edema)
2. Depletion of a-ketoglutarates: high NH4-->a-ketoglut converted to gluatmate(via glut. dehydrogenase)-->decrease of TCA cycle-->decrease oxidative phosphorylation(neurons dependent)

Front 40

Managements of urea cycle defects

hyperammonemia -->

treatments?

long-term?

Back 40

protein catabolism
hemodialysis
drug to conjugate glutamine

-reduce dietary protein intake
-provide adequate essential amino acids and non-protein calories
-drugs to create alternate paths for N excretion

Front 41

Catabolism of carbon skeletons of amino acids

Back 41

broken down into glycogenic/ketogenic products

glycogenic-->gluconeogeniss-->glucose
ketogenic-->lipid metabolism

-complicated pthways every step leaves possibility for mutation

Front 42

First step in degradation of phenylalanine

what is phenylketonuria?

Back 42

-Synthesis of tyrosine
* requires tetrahydrobipterin cofator, biopterin from GTP

dihydrobiopterin + NADH --> tetrahydrobipterin + NAD
*DHB reductatse

deficiency of phenylalanine hydroxylase which prevents conversion of phenylalanine to tyrosine or
deficiency of dihydrobipterin reductase(DHB reductase) or of biopterin synthesis

Front 43

Phenylkeotnuria management

Back 43

dietary:
-diet low in phenylalanine
-adequate other nutrients(tyrosine)
-diet must be instituted very early; neonatal screening essential
-diet must be maintained as long as possible

Maternal PKU:
-allows PKU women to reproduce
-offspring had multiple birth defects
-hyperphenylalanemia toxic to fetus
-must have stringent control of blood phenylalanine during pregnancy

Front 44

Phenylketonura problems and solutions

Back 44

cannot eliminate phenylalanine from diet,
avoid aspartame: aspartyl-phenylalanyl-methyl ester

Front 45

PKU II and other biopterin deficiencies
NTs affecteD?
treated by?

Back 45

tetrahydrobiopterin(BH4) is a cofactor for reaction in pathways leading to NT synthesis:

tyrosine-->L-DOPA
tryptophan--> 5-hydroxytryptophan(precursor of serotonin)

maybe treated by providing BH4

Front 46

Connecting glycolysis to lipogenesis
regulated by?

Back 46

Acetyl coA-->malonyl CoA
*acetyl CoA carboxylase

-allosteric
-hormonal: insulin
-phosphorylated is inactive
-dephosphorylated is active

Front 47

Fxns and Active forms of:
Glycogen synthase
Glycogen Pase
AcetylCoA carboxylase
Pyruvate kinase
PFK2(bifxnal)

Back 47

Glycogen synthase: deP
Glycogen Pase: P
AcetylCoA carboxylase: deP
Pyruvate kinase: deP
PFK2(bifxnal): phosphatase domain active in P-form, kinase domain active in deP form

Front 48

Opposing actions of Insulin and glucagon/epi:

Back 48

Insulin
+ glucose uptake, glycolysis(liver), glyocgen synthesis, fat synthesis

- gluconeogenesis, glycogen breakdown, lipolysis, ketogenesis

Glucagon/Epi
- insulin
+insulin

Front 49

Type 1 diabetes:

Back 49

-No insulin
-glucagon unopposed
-body keeps putting glucose into the blood, supply:
-ammino acids-->gluconeogensis
-FAs --> ketone bodies

Front 50

Type 2 diabetes:

Back 50

-insulin present but doesn't match glucagon
-milder type 1
-no ketone bodies, though can get ketone bodies if severe enough(eventually looks like type 1)

Front 51

Alternative Fates of glucose in cell

Back 51

G6P-->6 phosphogluconate-->ribose 5-P

also known as pentose phosphate pathway

Front 52

Pentose phosphate pathway
fxn?
rate is controlled by?

Back 52

synthesis of pentose sugars for DNA, RNA, ATP, NADH FAD,

generate NADPH from NADP+ for biosynthetic rxns


-NADP+

Front 53

Roles of NADPH

Back 53

1. Biosynthesis:
-FA
-cholosterol
-NTs
-Nucelotides

Reduced in Presence of NADPH
2. Detox
3. Reduction of oxidzed GSH erythrocytes:
-keeps hemoglobin iron in ferrous state
-stabilizes erythrocyte membrane

Front 54

1st step in pentose phosphate pathway:

need for?
lack of leads to?
effect on malaria?

Back 54

G6P-->6-phosphoglucono-d-lactone+NADPH+ H+ ---> 6 phosphogluconate

*G6Pate dehydrogenase
*lactonase, H20

NADPH genereation

hemolytic anema(heinz bodies), cells cannot maintained reduced gltuathione.

protective against malaria

Front 55

Cancer cells convert pyruvate to lactate even in the presence of O2 why?

Back 55

Need NADPH to make lipids
pentose intermediates to make DNA/RNA.

trade energy loss go get more glucose into pentose phosphate shunt