Concepts Of

Concepts of
biochemistry
Biochemistry
up to 24:FED

from 12to 48h:FASTNG

for 2to 46:STARVING

FASTNG:

glucagon
·

GH

qluco-corticoids FED:insulin

epineph.;NE
thyroid + #

ATP &
> CAMP * 5'ANP
>

adenyly cyclase phosphodiesterase

#

protein"Kinase A

phosphorylation of enzymes
FED State >
anabolism catabolism <
FASTING state

" V

insulin glucagon
+ +
✓ "

phosphodiesterase adenylyl cyclase

v u

^^
vi. CAMP CAMP

v u

""
in protein kinase A protein kinase A

v v

dephosphorylated stale phosphorylated state

: anabolic enzymes active in catabolic active in

. are .
:
enzymes are

de phosphorylated state phosphorylated state

"

exception : ATP citrate lyase : anabolic enzyme of FA synth .

active in phosph state

.
 Insulin Glucagon
activates all anabolic pathways activates all catabolic pathways
+ except glycolysis ; link reaction

2 catabolic pathways
( glycolysis ; link reaction )

Anabolic & Catabolic Pathways

KREB 's cycle

TCA CTA ; ETC : always occurring ; not affected by hormones

amphibolic : anabolic + catabolic

ANABOLIC pathways : cytoplasm >
source : HMP pathway : MAJOR

req .
ATP ; NADPH malic enzyme

> . : are ENDERGONIC

CATABOLIC pathways : mitochondria except glycolysis ; glycogenolysis ; gluconeogen .

produce NADH ; FADHZ , enter ETC

ATP is transferred to cytoplasm by < produce ATP

v ADP -1717 translocase

"
used by anabolic react v

i. are EXERGONIC

>

Pathways occuring in cytoplasm + mitochondria

-

always begin in mitochondria > 1st enzyme is always present in mitochondria

gluconeogenesis
-

urea cycle
heme synthesis

Body Fuel
starvation
a

qg
food intake

I 1 1-
late starvation
early fasting :
fasting : :

liver glycogen B- oxdn of FA B- oxdn Of FA

gluconeogen . KB synth .
 Fasting or Starvation state :
pref fuel
. : FATS

adipose tissue breakdown >

release of FA >
enter LIVER

release of acetyl CoA < B- oxidation of FA

3 fates of acetyl CoA : -

TCA cycle
-
KB synth .

activn of 1st step of gluconeogenesis

-

DM : insulin > GLUT-4 ; 8 acetyl CoA > glucose

v v

glucose cannot enter cells fats > carbs

cells assume they are starving

KB synthesis > seen in urine ( as in DKA )

i. DM -
fasting starving

Fuel in different states for different organs :

usually fed : glucose
tasting : FA

exceptions : brain .

fasting > glu starvation : KB

heart .
fed >
FA

liver . starvation > AA

adipose . starvation , FA
 °"°"""""""
brain glu glu KB

heart FA FA KB

muscle glu FA FA ; KB

liver FA AA
glu

adipose Glu FA FA

RBC glee glee glee

fetal heart ; heart failure > glucose > calorific value of FA >
glucose
adult heart > FA

FA : cannot cross BBB

liver AA ; liver cannot KB due to lack of

starvation use
enzyme thiophorase
-
>

fed TCA ; FA synth

Fates of Acetyl-CoA >
: .

fasting : TCA ; activate gluconeogen .

starvation TCA ; KB synth ; activate

: .

gluconeo .
 Acetyl-CoA in Fed & Fasting states
FED State

> acetyl CoA > FA synth .

+
insulin > pyruvate dehydrogenase
^

FASTING state _ pyruvate 01717

-1

" " "

+
B- oxidation of FA > acetyl CoA > pyruvate carboxylase

1
1st step of gluconeogen .

Diabetes Mellitus
DM insulin
fasting / starvation
'

> > anabolic enzymes >

-

hyperglycemia
°
↑↑ B- oxidation of FA
11
↑↑kB synthesis acetone
-

>
KBS : C -
C -
C C -
C -
C -
COO

gluconeogenesis acetoacetate
-

↑ VLDL B. OH butyrate C -
C -
C -
COO

↓ lipoprotein lipase
HYPER -
K+ >
-
due to ↓ insulin . acidosis : actin of HI /Éantiporler
DM > TCA cycle suppression due to :↑↑ utilization of acetyl CoA for KB synth .

017A >
gluconeogen .

B- oxdnof ↓NAD+ availability

"
↑ FA >
↑ utilization of NAD >

Important Structures

C- C- COOH HOOC -
C -
C -
COOH C -
C -
C OHC -
C -
C
11 11 I 1 I 1 I

0 0 OH OH OH OH OH

pyruvate 01717

glycerol glyceraldehyde
C- C- COOH HOOC -
C -
C -
COOH

propionic acid succinic acid

C -
C -
C C -
C -
C -
COOH C -
C -
C -
COOH
11 11 I

0 0 OH
acetone acetoacetate 13-01-1 butyrate

addition of high energy bonds : Poa ; CoA .

> req ATP except with
.
:

-
G3P > 1,3 bis PG .

thiophorase : in KB utilization
G3P adds CoA to acetoacetate
dehydrog .
 Dietetics
ATKIN 'S DIET : ↓ ↓ calorie + ↓↓ carbs NORMAL DIET : GO -70% carbs

20% lipids
KETO DIET : Ht , absent carbs
exogenous : transp by.

<

chylo µ
SEDENTARY LIFE :
50% of carbs .
:
utilized
10 t.com/. to glycogen
:
40 t.com/. to fats endogenous : transp by VLDL
-

> .

carb rich + fat free diet > continues to become obese

lipoprot . increased : VLDL

Specific Dynamic Action (or) Diet Induced Thermogenesis

v

energy req .
to digest + absorb +
transport + metabolic e

PROTEIN > CARBS > FAT

 Enzymes
Enzymes
/

EC ENZYMES MECHANISM -
EXAMPLES

1 Oxidoreductases dehydrogenase ; reductase

2 transferases kinase :
organic 1304 ; phosphorylase : Pi

3 hydrolases add H2O to break bond : phosphatase

4 lyases make / break bond +

motto / ATP : synthase
PEP carboxy kinase ; decarboxylase
5 isomerases

6 ligases make bond + use ATP : synthetase

carboxylase

Oxidoreductases : Dehydrogenase ; Reductase enzyme of

gheconeogen .

dehydrogenases : remove
-
H > accepted by NADP ; FAD ; NAD

NADH : 2.5 ATP

FAD Hz : 1.5 ATP

NADPH : reductive bio synth .

NADPH sources : HMP pathway
malic enzyme : NADP -
malate dehydwg .

cytoplasmic isocitrate dehydrogenase

anabolic pathways use NADPH v

v

cytoplasmic mitochondrial

v v

coenzyme : NADP coenzyme : NAD

NAMING :

dehydrogenase : subs .

getting oxidised

reductase : subs .

getting reduced

^
add ATP
Carboxylation > of CO2 using : LIGASE > Carboxylase

"
carboxylase :
req .
A : AM > req .
Mg
B : B > ( biotin )

C : CO2

" "
when an enzyme uses ATP > req .
Mg Mn as a cofactor : carboxylases
kinases

kinases : use ATP > .

:
req .
Mg
"
except pyruvate kinase :
req .
É >> Mg"
 oxidative simple
De-Carboxylation >
either

OXIDATIVE DECARB .
: uses
dehydrogenase + 5- co enzymes
-
: Boy : thiamine

Bz : riboflavin
Bz : niacin

pantothenic acid is a constituent < Bs : pantothenic

of CoA Lipoic acid

SIMPLE DECARB . : uses decarboxylase

teq.BG : PLP

11

AA >
amine ; AA >
keto acid

" -1

coz COO MHz

1. CO2
,

C -
C -
C -
C -
C -
COOH ,
C -
C -
C -
C -
C
I 1 I 1
decarboxylase ; PLP
MHz MHz MHz MHz

lysine : di -
AA ; 6C cadaverine : di amine ; 5C
-

foul smelling
2. CO2
,

HO -
C -
C -
COOH ,
HO -
C -
C -
N Hz

HH ,
decarboxylase ; PLP

ethanolamine

serine : OH containing
-

3C AA
3. n CO2
HS -
C -
C -
COOH > HS -
C -
C -

MHz
,
decarboxylase ; PLP
MHz
mercapto -
ethanolamine

cysteine : SH containing
-

3C AA

4. -iTÉOz
HOOC -
C -
C -
C -
COOH >
HOOC -
C -
C -
C -

MHz
I

NHZ decarboxylase ; PLP

glutamine : 4C

glutamate : 5C ; dicarboxylic AA

5. MHz MHz NHZ

I 1 I

C- C- COOH C -
C -
COOH C -
C -
COOH
1 I
> >

PA -
OH lase Otllase
'
I 1 OH
PA
OH OH
tyrosine decarboxylase
decarboxylase PLP DOPA PLP

1- V

C C MH C -
C MHz
-
- -

I 1

'
OH
1
61-1 tyramine OH

dopamine
 Rossmann Fold
super 2° structure E alternating 13 strand ✗ helix 13 strand : .
: called 13×13
seen in
enzymes c- dinucleotide co -

enzymes told
( NAD ; FAD ; NADP)

ROSSMANN ENZYMES :

G3P dehydwg .
alcohol dehyd glutathione reductase

phospho glycerodehyd
-
. lactate dehyd . D- AA oxidase

isocitrate dehyd .

Ce
Cell
Organees
organelles
membrane bound Str .

RIBOSOMES : rRNA + protein ; not memb bound .

> not organelles
nuclear membrane > Outer + inner > continuous c- ER

NUCLEOLUS : rich in rRNA

mt DNA ; RNA ; ribosomes synthesise

Mitochondria = Power House > .
:

10% of Mt .
proteins
maintains cytoplasmic Ica"I 20% of ETC

OMM : contains lipid metals enzymes . interment space . : nucleotide metals enzymes .

IMM : ETC mt matrix

.
: Boxdn FA ; TCA ; glutamate dehyd .
 Lysosomes : Digestive organelles >
Contain hydrolases ; pH < 5

LYSOSOMAL STORAGE DISORDERS :

catalase peroxidase
Peroxisomes/Microbodies/Glyoxysomes > ;

neutralising 1-1202 + Oxdn Of VLCFA + ✗ -

oxdn of FA no ATP formed

ZELLWEGER SYND . : peroxisome biogenesis disorder

also called Cerebro .

hepato . renal synd .

 Endoplasmic Reticulum

V V

granular : RER : ribosomes agranular :S ER : no ribosomes

v v

protein synthesis lipid synthesis +

drug detox .
in liver

during cell fractionation RER disrupts G forms

:
µSomes
v

method to separate cell organelles while preserving function

separation of cell
organelles > sucrose density gradient centrifuge

Golgi Apparatus/Dictyosomes/Packing bodies

active in cells exporting proteins
protein packing +
sorting >
0 -

glycosylation : GA ( GOA )
protein 0 -

glycosylation
membrane synth .

of peroxisomes ; lysosomes >

N -

glycosylation : ER

Bonds in Macromolecules
strongest : covalent covalent > ionic > H -
> hydrophobic > Vanderwaal 's

weakest : Vanderwaal 's

strongest covalent : PEPTIDE

 Biomarkers of Cell Organelles

. . .
acid ph -
tase

Yg
- \ -

%Dh]H
SDH

_ DNA
.
.
polymerase
'
. catalase

88g
"
"" "" "" ° "

M
Galactosyltransferase
GGP tase
-

Nci K+ ATPase
-

adenylyl cyclase
'
5- nucleotidase