ONCOGENESIS COMMON ONCOGENES :

BRAF and RAS (colorectal cancer)

steps in carcinogenesis
cDK4 and ERBBZ ( Breast cancer)

PT-3.CA and C- MY C (lung & Bladder cancer and Lymphoma)

•
INIT/AT/ON - normal cells become exposed

rapid irreversible genotoxic

, ,
ONCOGENE ACTIVATION :

<
Mutation -
alterations in coding (ex Point mutation)
.

activates
- PROMOTION -
clonal expansion of initiated cells .
Promoter Insertion
c- MYC gene
proliferation
-
↳
cell

Enhancer Insertion
" " activates promoter region
preneoplastic lesion
-

.
w/ in cell genome ; down or upstream

chronic , epigenetic ,
reversible . Chromosomal Translocation -
joins fragments
of chromosomes

Development of cancer cells due to

-

often seen in myeloid or lymphoid tumors

↳ Ex Philadelphia
:

chromosomes produces BCRIABL Tyrosine kinase

>
Oncogene activation /
.

→
excessive WBC production
BCRIABL Fusion protein gene
> Inactivation of Tumor Suppressor Gene ( TSG) →
marker for chronic myelogenous leukemia CCML)
Gene Amplification expansion copy member
-
in
> Alteration of DNA repair mechanism .

of a gene
↳ Ex . Her 2 Gene at chromosome 17
b
- PROGRESSION -

preneoplastic
> malignant
cell overexpression → Breast cancer
"
clinical cancer
" (Trastuzumab anti Her 2 drug ) - -

t latency period for tumor formation

POINT MUTATION
•
METASTASIS spread of -
cancer cells via :
single Nucleotide substitution -
most common disease -

associated point mutation

> est of tumors i. Invasion
insertion deletion of pair
.

-
or base
and distant
2.
Migration
metastasis NOTE : RAS mutation impair the conversion of GDP → GTP !! !
promotes proliferation
ONCOGENE
or

PROTO
-

' -

cell survival TYPES OF POINT MUTATION :

when nucleotide
Ex . GF , Signal Transduction Proteins , Transcription Factor ,
silent mutation -
same protein
change produces the
Apoptosis Suppressor Gene
Produces a stop codon ; becomes non -

Nonsense Mutation
functioning protein
-

• ONCOGENES -
mutated proto-oncogene missense mutation
- encodes different AA

↳ primary driver of cancer •

Conservative -
different AA , same property
! Non conservative different AA different property
Types
• - -

> Viral Oncogene from persistent viral infection-

Ex Hepa Bdg HPV → cervical cancer

FRAME SHIFT MUTATION
.

> Cellular Oncogene -

activated form of proto-oncogene -
insertion or deletion of nucleotide that shifts the
a
way
Ex . Burkitt lymphoma 2 sequence is read
( RAS gene alteration)
colon cancer ↳ mutation → DNA
sequence read incorrectly → Malfunctioning
protein

classification :
pick up -

signal
>
Signal Transduction Pathway -
then proliferate
IX. Secreted GF ,
cell surface Receptors ,
Intracellular Transducers ,
DNA -

binding Nuclear proteins

When affected cells become

>
Apoptotic pathway
,
.

immortal
EX .
Regulators of the cell cycle
TUMOR SUPPRESSOR GENE → 2 Enabling characteristics :
recessive and highly conservative > Genomic Instability & Mutation
-

> Tumor
Promoting -

Inflammation
Knudson's Two Hit
→
Hypothesis -
cancer cells attract cells of the innate immune system
other hallmarks
↳
requires bi allelic to inactivate both gene that contribute to
acquiring
•
Hereditary Cancer

First Hit : Inherited or somatic; person becomes susceptible 1 .

Sustaining Proliferative Signaling
2nd Tss ↳ most fundamental trait
Second Hit :
Acquired ; inactivates
Normal cells -
careful control in production
•
Sporadic cancer "
cancer cells -
"
masters of their own
destiny
↳ 2 acquired mutations
Platelet-derived GF -
Induction of intima / thickening

Transforming GF -

Regulation of angiogenesis
PROTOTYPE 956s :
VEGF & Insulin like GF -
- Stimulates proliferation
> Retinoblastoma ( RBI) gene
> Tumor P53 (TPb-3) gene Cancer Cell's ways to sustain Proliferative
"

↳
Signaling
"
Guardian of the Genome i

↳ most common
genetic alteration 1 .
Production of GF Ligand
2. Autocrine stimulation
DNA REPAIR GENE 3. Paracrine stimulation of Normal cells

checks and corrects mismatched pairs 4 Increased

-

.
Receptor Expression
-

mutation → microsatellite instability ( Mst )

5. Growth Activation
↳ multiple uncorrected RNAs
Signaling Pathway
↳ Rds / Raf
pathway for survival (regulate cell growth)

single Mismatch pathway (energy metabolism)

> ↳ mTOR

MSHZ Ms 11-6 mismatch

and
recognize
-

MLHI and PMS 2 -

initiate repair RAS PATH WAY

Normal cell ras GAP GTP GDP

hydrolyzes
-
→

> Insertion / Deletion Loop ↳ inactivates Ras

MSHZ and MSH 3 -

recognize error
↳ control w/ in pathway

MLHI and MLH 3 - initiate repair cancer cell - Ras is mutated

↳ cont activation uncontrolled

signaling
→
of
growth
.

HALLMARKS OF CANCER
1.
Sustaining Proliferative Signaling
NOTE : Ras mutations are drivers of Oncogenesis
↳ most
2.
Evading Growth Suppressors difficult to treat

3. Activating Invasion and metastasis

4.
Enabling Replicative Immortality
5.
Inducing Angiogenesis
a- Resisting Cell Death

Immune Destruction Der 't in

Evading
] Epigenetics
7.
Genetics and
8.
Deregulating Cellular Metabolism / Energetics
9. Genomic Instability du mutation
]
10 Tumor
Promoting Inflammation
-
-
 2.
Evading Growth Suppressors 5 .

Inducing Angiogenesis
Due to : Pre -

angiogenic State : PEX . TSP 1-

,
PEDF ( Angiogenic Inhibitors)

Inactivation of -156 VEGF (

Angiogenic stimulator
•

> RB Gene -
Found at G1 checkpoint prior S phase Bevacizumab -
anti -

angiogenic drug
↳
phosphorylated → releases EZF w/c binds to DNA → gene ↳ monoclonal
antibody
trans .

+ cell ↳ binds to VEGF

↳ Dysfunctional : unbound unregulated

progression

RB Gene →
eat
a"
growth 6. Activating Invasion and Metastasis
metastatic cascade -

physical translocation of cancer

conditions cells
>
p53
-
activated by abnormal
↳ cell arrest
cycle
↳ extreme conditions :
apoptosis EPITHELIAL MESENCHYMAL -

TRANSITION
• Evasion Of Contact Inhibition
Activated by: SNAIL , SLUG TWIST 1 , and ZEB
,
42
↳ metastatic Initiation Gene
Normal cell -
WI cell to all adhesion (E-cadherin )
- -

cancer cell -
no cell-to-cell adhesion → tumor at mass → reversible plasticity ( mesenchymal tumor → epithelial )
ce,, tumor cell

corruption TGF p Pathway

• -

of

> Epithelial -

mesenchymal Transition -

migratory and invasive CARCINOGENS

property
Endogenous : ROS , Chronic Inflammation

3. Resisting cell Dedfh Exogenous : Chemical carcinomas . Radiation ,

viruses

Apoptosis -
controlled by p53 and p 21 ; shrinkage
Necrosis -
swelling ; release contents ( inflammatory cytokines) Vinyl Chloride
-

Hepatic Angiosarcomz
nutrient def ↳ rare tumor in the liver
Autophagy -
induced by .

↳
paradox :
protective for cancer cells

↳
favors cancer cell survival

✗ p53 apoptosis -

A BCL 2 cancer cell

anti-apoptotic
-
-

V1 cytochrome C -

apoptosis
caspases
°
Initiator ( 2,9 , 8,10) -
signal production
°
Executioner ( 3,617 ) -

def-ragmenta.tl on

4. Enabling Replicative
Immortality
indefinite replication
-

2 Barriers of Proliferation :
> Replicative senescence -
non -
proliferative, but viable

> crisis cell death after

-

replicative senescence
AMINO AUD CHEMISTRY , POLAR (I love water ! -
Polar Bears ) -

forms salt
orionicbond
bridges

DIGESTION , G ABSORPTION POSITIVE

[ imidazole
NEGATIVE
HIS GLUTAMATE
] carboxylic Acids

/
Nitrogen
ESSENTIAL AMINO ACIDS Elxs can b-
ASPA loniuddt pH 7-
protonated
PHENYLALANINE -
precursor of Tyrosine ARG lower
↳ guanidine
pH value
+ -
tonic Bond

✓ALINE
" "
salt bridge

TRYPTOPHAN -
Indole side chain POLAR , UNCHARGED - contains OH or amide

THREONINE SERINE
] contain OH
]
sites of
primary linkage
ISOLEUCINE THREONINE of sugars to proteins

METHIONINE -

Sulfur for cysteine ASPARAGINE ↳

forming glycoproteins
] contain amides

HISTIDINE -
Imidazole side chain GLUTAMINE
ARGININE -
Semi essential
-

(
can be
synthesized
via a-tmliine )
from
CYSTEINE sulfhydryl group
glutamine
-

(E""NE stabilization of protein structure

] Purely ketogenic
-

sulphydryl snlphydryl disulfide

LYSINE CYSTEINE 1- CYSTEINE > CYSTINE

NON -
POLAR (B•⑨hoB These are
fat lumps)
NON ESSENTIAL AMINO ACIDS ALIPHATIC
- -
open
chain
AROMATIC chain closed -

CYSTEINE From serine; requires sulfur ( from met)

Gly P HE ring

/
Benzene
-
-

ALANINE pyruvate Trdnsamination

-

(Eu TXR -

Phenyl ring w/ OH group

↳ "" * s" - "
A" side "" " T" ' " "" " "
↳
ASPARTATE From CAC -

MET saturated Hcs

TYROSINE From phenylalanine(via hydroxylation)
-

VAL > high hydroFatty

SENNE -

From 3- Phosphoglycerate ( Glycolysis) y ,E index

PRO
NEAA's can be
formed from :

>
Glycerite 3- Phosphate → Serine Cysteine
⇐ METHIONINE
-

does not contain a

sulfhydryl group
-

>
pyruvate →
Alanine Glycine ↳ cannot form disulfide bond w/ another sulfur -

Oxaloacetate Aspartate Asparagine containing AA

[j Threonine
> →
-

transfer methyl group

> ✗ -

ketoglutarate

↳ Glutamate > Glutamine

[, PROLINE -

cyclic iminoaeid
Proline
contains R
pyrrolidine ring
-
-

↳
forms kink → causes abrupt changes in the
direction
BOTH CTUUCOGENIC d. KETOGENIC
PHENYLALANINE
ISOLEUCINE
THREONINE
TRYPTOPHAN
TYROSINE
PURELY KETOGENIC
LEUCINE

LYSINE
Any His Met Cys
RELATED DISEASES ✗ -
Helix -
rod-like structure

PHENYLKETONURIA "
due to
phenyl acetic acid ↳
every 4
"
-
odor -

residues there is H bond

mousy , an -

↳
Phenylalanine hydroxylase (PAH ) ↳ winds R clockwise

↳ Phe Tyr Glycine disrupts the coil

→

proline
]
Hypopigmentation
↳ restricts movement of ✗ helix
↳ lnh Tyrosine hydroxylase
-

.
of
/ due to pyrrolidine imine ]
↳ Tyr → DOPA and melanin group

ALKAPTONURIA - "
f-
black urine disease
when exposed
"
to air
§ -
Sheet -

-
often
polypeptide
contain Tyr
becomes
,

:
Ile , and Val

arrigged
↳
homogentisate 1,2 dioxygenase deficiency parallel

↳ Tyr anti-parallel
phe
]-0 >
Homogentisic
Acid
→
Acetoacetate
Fumarate

TERTIARY -
3D structure

MAPLE SYRUP URINE DISEASE ↳ interaction between R

groups
↳ BCKD deficient biologically active
-

Hydrophobic AA cluster inside ; promote 3D folding

Hypoglycemia enzymatic block gluconeogenic receptors
-
-

severe acidosis -20×0acids Hydrophilic AA -

surface ; contact w/ water

> Prevent food rich in BOAA It -

leucine , L isoleucine , L valine)
-
-

> High calorie diet

Secondary Interactions

150ELECTRIC POINT - H -

Bonding ( bet carbonyl oxygen group.

du amide hydrogen )

its zwitterion Ionic Bonding ( bet oppositely changed groups)

→ AA in
-
2
form
.

↳ Ex -
Lys (t ) and Asp C- 7

p KI t pkz -
Van der Waals Forces - AA residues repel each other

pI
=
Hydrophobic Interaction bet NP AAS
-

- .

2 Ex Aliphatic AA

]
.

sulfur containing AA water molecule

explodes a
-

PROTEIN STRUCTURAL Proline and Glycine

ORGANIZATION -
Disulfide Bonding

Ex
Amino
.
cyst Cys →
cystine
H⑤ met
Acid cyst
Amino
Acid
# Polypeptide chain
ay , +
cystine
]✗ not possible

PRIMARY -
AA sequence ( held by peptide bond) QUATERNARY -
when a. protein has subunit
proteins
Ex .

Hemoglobin
- 2 or more peptide chains
SECONDARY -
Folding or coiling ( via H bond )
-
↳ tetramer ( 2×+2 @ )

-
✗ helix 1 Globular )
- ↳ between carbonyl
e-
B- Sheet ( Fibrous) Oxygen group and
amide hydrogen of '

another
PROTEIN DENATURATION Huntington's Disease aggregation huntingtin from its
-

of
↳ proteins lose their structure mutation

structural Denaturation = Loss of Biological Activity

Factors Affecting Protein Denaturation :

DIGESTION
> PH In the stomach :
autocatalytic
→
>
Temperature Pepsinogen Pepsin
> Acids / Bases Chief cells )

> Pressure HCl -

secreted by gastric parietal cell
> Detergents

> Agitation (when beating the egg) Xp H -

pepsin is not denatured →
endopeptidase
↳ cleaves peptide bonds
↳ carboxyl groups are
PROTEIN FOLDING provided by aromatic
and acidic AA
↳
for protein to function must fold into correct conformation
properly ,

Assist in Protein Folding :

In the Pancreas :
>
chaperones or Heat Shock Proteins Bicarbonate is secreted

↳ utilize their ATPase to provide energy from ATP

↳ neutralizes the stomach acid → MPH
↳ activates
> Disulfide Isomerase proteases

most
Trypsin specific
-

-7 Protein is carbonyl group provided by Lys or

Arg
Error in
Folding
-

polyubiquihdted Chymotrypsin
-
less specific nonpolar

degraded
-

carboxyl group ( from PTT + Len and met)

Imperfect - misfolded protein will require Elastase -

carboxyl group (small tide chains)

(Ala , Gly fer )
protein Ubiquination →
proteasome →
degrade ,

carboxypeptidase A : releases
hydrophobic AAS
PRION DISEASE B releases basic Arts
!
His Lys Arg
-

spreading of misfolded prion proteins

-
normal ✗ helix
-
→ abnormal
p pleated sheet
-
In the Intestinal Cells :

>
Creutzfeldt-Jakob Disease Aminopepsidase
> Gerstmann -
Strausser ScheinKer syndrome
-

>
Fatal Familial Insomnia

> Kuru

>
Alper's syndrome

NEURODEGENERATIVE DISEASES
Alzheimer's Disease -
accumulation of :
amyloid @ peptide
Tau protein
-

pathsgnomonic : amyloid plaque

hallmark
neurofibrillary tangles

Parkinsonson 's Disease mutation of :X

Synuclein (SNC a)
-
- -

pdtho gnomonic Lewy ;

bodies
hallmark
 -

AMINO ACID METABOLISM I CYSTEINE -

by-product of methionine degradation

met 1- ATP > SAM

methyl
Amphibolic Intermediates SAM
→
>
Adenosine
SAH becomes essential when
met is
Glycolysis TCA say
→
>
Homocysteine inaugurate Foritssx
precursor
of
> 3- Phosphoglycerate > ✗ -

ketoglutarate
↳ SH
group (from Sop
met ) cystathionuni
in
,
taurine

PLP I cysteine
7*-2 ketoglutarate
-

serine Glutamine
Homocysteine
-

✗
-

+ serine >
cystathione -

Glycine Glutamate
CBS Ammonium ions
J
-

. Ch N atoms (from serine)

-

Cysteine -

proline Homocysteinutia
•
S group Cfrom met )
>
pyruvate -

Arginine (→ Pyruvate
-
Alanine > Oxaloacetate n → urea

5 →
sulfate
-

Aspartate →
sulfuric Acid ( wire)
-

Asparagine
→ PAPS (sulfate donor)

when is needed :
energy
SERINE -

major sites are liver and

kidneys Hdesulfhydrase
Hzs

1st :

secondary -
OH > keto Group > Keto Acid Homocysteine ¥ ✗ -
ketobutyrate
Ntty
0
2nd : Transamination (from Glutamate) w/ PLP

1, 3rd : → L serine
-
( via Hydrolysis w/ Pi released )
ALANINE
e

or
↳ precursor of Selenocysteine (Found in Glutathione peroxidase)
Mserine= -
Phosphoserine Phosphatase ↳ pyruvate will undergo transamination

Donor :
Glutamate

M I N O R Acceptor : PLP

P " + THE
L Serine
Glycines Transferase > -

Glucose -
Alanine cycle

GLYCINE Alanine predominant AA prom muscles

-

For energy use

-

M A J ° R +1C
.
.
- → N5
-
NIO -

methylene FHY
ÑÑ
- -

serine's
.
.

F ""
>
Glycine
SHT
Cori
cycle
carrier of 1- carbon unit Lactate anaerobic glycolysis in RBC (product)
FHY
-
-

(
skeletal muscles
From
exercising
-

↳ muscle pain
other carriers :
> Starvation :
uses ketone bodies ( alternative )
Biotin -
cofactor in carboxyl dtion
-

1- carbon donor ( coz ]

S-Adenosyl methionine ( SAM)

-
1- carbon carrier cats) AAS from ✗ -

ketoglutarate
-
NE > EPI
amination
rang
acetyl-CoA +
Glucose > ✗ -

ketoglutarate → Glutamate
serine
-

M I N O R
Cvid d-AA oxidase) I 1 1
"P
Threonine Glycine Converted to Gly oxalate
Arginine
>
Glutamine Proline
-

threonine
Aldolase -
cozt Ammonia
(via Glu ( via Ornithine)
-
donated to
Flty aldehyde)
oxidation
Glyoxalate > oxalate
Glyciner
Trdnsayynination
↳ calcium oxalate stones
GLUTAMATE -

precursor of glutathione A-As Related to Oxaloacetate

AST
Glutamic Acid Asparagine
Aspartate [ Glutamate
]→
oxaloacetate s >

cysteine Glutathione → GSH

( reduced Form )
GEEK
Glycine
f potent Antioxidant

CYS Gly , whitening Aspartate -

preferred for Purdnpyr synthesis in urea cycle

Linh tyrosinase)
Glut'd bet -

MO ? Asparagine -
needed by cancer cells in order to proliferate
Glutathione as Antioxidant -
ANTI-CANCER (malignant cell die
In to less toxic:( Oxidation)
Glutathione → potential
It 202
sites
of TYROSINE
Peroxidase production
:
2 GSH GSSG
>
Ubiquinone Phe P¥H→ Tyr
>
complex 2 of ETC
PKU

potent Antioxidant :( Reduction) Per

-
ALA -
em ;a
] microcephaly
mental retardation
Glutathione Transamination
Reductase
Gssg > 2 GSH > Phe →
Pyr
NADPH

/
OXIDIZED → phenyllactate
DECARBOXYLASED → phenyl acetate
GLUTAMINE "
mousy odor
"

Glutamine f Amination )
-

Glutamate sisnthdse Glutamine

>
ATP NHS ↳ Plenty in the brain SX OF PORPHYRIN
succinyl CoA COASH + CO2
ATP → ADP 1- Pi

Ammonia)
g, ,ygn , y 27 Aminolevulinic Acid
Y
-

cmaior mechanism of
handling y ALA synthase
.

Glutamate Synthase Deficiency PLP 1- HI

malformation & Death
↳
severe brain

Good : 61nF Glu ( egg toxic Glycine ✗ ]→ Anemia

•
LTIUDH II
'
Pyridoxine
°
CPS 1

CREATINE
PRO LINE creatine -

from Gly +
Arg ( methylated by 5AM )

Glutamate semialdehyde → unstable Creatine Poy stored

energy ; reversible
→
pyrroline
- -
-

5-
spontaneous carboxylate Creatine ; irreversible ; measured For
creatinine -
creatine 1- Poy
cyclization renal function

↳ reductase

hydroxyprolines collagens PROLINE SEROTONIN

uses vii. c
catabolism

ARGININE -
essential during infancy 1st pathway : MAO (Deamination) →
SAM / methylation )
1st : Intestine 2ndPathway : 5AM ( methylation ) → MAO ( Deamination)
Ornithine ( intermediate cycle)
→ in urea

ASPARTATE major excitatory NTCspinal cord) -

2nd kidneys
:
GLYCINE major inhibitory NT(spinal cord)-

citmlline > Arginine > urea (urine)

④ -
vasodilation Ornithine ( back to mitochondria)
 steps in -13 and Ty synthesis : UREA CYCLE
•
concentration Transamination -

N NHY and Asp

as

• Oxidation Trans deamination - Glu deamination

•
lodi nation -

amino N →✗
-

K→ L Glu
-

•
Coupling
•
Hydrolysis

☒
SYNTHESIS OF :
PURINE BASES
C 4. C5 N7
Glycine
-
,

Glutamine -
N3 , N9

Aspartate - NI

N 10 -
FTHF -
C2 ,
C8

coz -
C6

PYRIMIDINE BASES
Aspartic Acid C5,06
-

Glutamine -
N3

THF
4 Atoms :
NS.N7 NI NIO
Hydrogen , ,

Tx for
Hyperammohernia
Benzoate

Glycine
1-
]→ HIPPURATE

Phenyl acetate

Glutamine
1-
]→ PHENYLACETYL GLUTAMINE
-

ASPARTAME -200 ✗ sweeter

Aspartic Acid
→
in caution to px
w/ PKU

TPhenylaianineFAspartame.gr
AMINO ACID METABOLISM 11 PROLINE

proline → Dehydroproline → Glutamate → Glutamate → ✗ -

keto

AA structure : proline semialdehyde

Glutamate
DHX semialdehyde
Cti carboxyl Group
Type I
DHX
C2 :X Carbon TYPE#
Hyperproiinemia
Hyperprolinemia
C3:R Group

GLYCINE -
Ammonia
'
Carbon Skeleton Catabolism
Glycine ✗ -
coz
Glycine
ketogenic AAS
synthase NSN '° Methyl THE
-

complex
-

> A# ↳A

>
Acetoacetylcsn
]→ Ketone Body Synthesis Glycine Encephalopathy
( Purine du Pyrimidines)

Non ketotic
Hyperglycemia
-

Glucogenic AAS -1 oxalate

Glycine → Glyoxylate
kidney
> TCA intermediates → Pyruvate →
Gluconeogenesis stones

(Asparagine → Aspartate)
ASPARACTINASE -
used to treat lymphocytic ALANINE
leukemias and lymphomas Transaminase
↳ aids in tumor growth
① Alanine
PLP
> Pyruvate
Because Asparagine
↳ precursor : Vit.BG

② ✗ ketoglutarate Glutamate
ARGININE
-
>

↳ Nitrogen
( when it accepts AA from PLP )
atom CCG )
NH3
keto
Arginine > ornithine → semialdehyde > Glu ✗ precursor of Primary
-
.

Bite Acid :

Amino Acceptor :X -

ketoglutarate CYSTEINE > Taurocholate

Donor ?
>
Taurochenodeoxycholate
Amino collector : Glutamate M A J O R

Red -
Mt ° ""
T
Glycine Cystine >
cysteine > eystein supinate > Taurine
5AM CK
\ > Guanidine acetate
Arginine
t
> Creatine -
ATP
Phospho
creatine
-

PAPS ' sulfate 1

"i '
Bisulfite ✓
Ornithine
p sulfinyl
-

pyruvate
Folic Acid Deficiency
-

Gluconeogenesis Pyruvate
HISTIDINE
↳
9F1GLU
Becausethere won't ^

Histidine → Urocanate >

4- imidazolone -5
propionate
-
Proceed w/ ° FA
> Fl GLU )
Histidine Ammonia
itagheconeogenite AA ( produce energy)
µF¥ M makes
I N 0 R -

wax sulfite
""" mint"
Histidinemia
2- Ketoglutarate < Glutamate cysteine ? 3- mercaptopyruvate \ > Pyruvate
1-

Urocanic Aciduria Thiosulfate

• mental Retardation Hzs
•

Delayed speech
RHO DANESE -
incorporates sulfur promthiooysteine
and thiosulfate
> Histidine decarboxylation > Histamine
✓ tries to detoxify cyanide
 THREONINE 2 Most Important Amino trans -

MAJ 0 RC ketogenic)
f-erase Reactions:
Threonine 7 Acetyl-CoA AL -1
Hepatic Diseases

Alanine > Glutamate

↳ source during prolonged starvation
Oxidative
Deamination
M I N O R ( Gilucogenic)
Nonhepdtie Diseases
As,
Threonine > succinyl-CoA > Krebs cycle
Glutamate Aspartate
>

Amino Group
: d-Ketoglutarate
collector

HYDROXY PROLINE >

Pyruvate
-
wound
healing Aspartate -
source
of Nitrogen in
urea
cycle
FUMARATE
Phe > Tyr > P -

Hydroxy phenyl pyruvate

SELENO CYSTEINE
rate-limiting integral component of glutathione peroxidase
-

step
-
GSSG → GSH
Fumarate : makes the d. Tyr GLUCOGENIC
b
Acetoacetate : makes Phe du Tyr KETOGENIC H 202 → H2O
Forms serotonin
and
melatonin

TRYPTOPHAN /
11C Atoms

> 1C Formate
are Initially Converted Into :
¥
> 3C Alanine -
makes Trp GLUCOGENICAA

> 3 Coz

4C
acetyl
> CoA

2-amino -3 -

carboxy muconic
semialdehyde
NAD / Nappt
"

3% -
converted to

97% -
converted to picolinate 4 glutarylcs A
?⃝
 METABOLIC INTEGRATION I

LYSINE
do NOT
THREONINE = undergo
PROLINE TRANS AMINATION

HYDROXY PROLINE

UREA CYCLE
i. Transamination .

Alanine
product
:

major
-

2. Oxidative Deamination
☐ ☐"
- Glutamate > a -

ketoglutarate
NADINADP
? -
→ Ammonia ( will undergo
urea cycle)

3. Deamination liver
-

Ammonia from other tissue 7 Glutamine

( non -
toxic ,

soluble form)
-

Glutamine
⇐" " " " "
Kaluta mate
↳ Ammonia → urea

cycle
METABOLIC STATES
Well Fed - 2- 4 hrs after meal

Early Fasting / Post absorptive -

4- 18 hrs after meal

state
Fasting
but <3 NPO
18 > hrs
days
starvation
> 3 days NPO

Glycogenolys is 24 hrs only

-

Gluconeogenesis -

after 24 hrs