DEPARTMENT OF BIOCHEMISTRY

HASANUDDIN UNIVERSITY
ROSDIANA NATZIR

Only 3 paticularly metabolites important

representative in intermediate metabolism :
1. piruvate
2, acetyl coA
3. glycerol.

As a connecting link between metabolism of

protein, carbohydrate and lipid.-- through CAC
pathway --->
The cyclic pathway has both catabolism and
anabolism functions.
Waste product are : CO2; NH3 and H2O.NH3
incorporate into urea ----> excreted.

Makes ATP
Makes NADH = nicotinamide adenin
dinucleotide ( reduction ,H=hydrogen)
Makes FADH2 = flavin adenin dinucleotide
(reduction, H=hydrogen).
Requires some carbohydrate to run

Glycolysis in the cytosol

Krebs cycle in mitochondrial matrix
Mitochondrion

Outer membrane very permeable

Space between membranes called intermembrane
space .

Inner membrane (cristae)

Permeable to pyruvate,
Impermeable to fatty acids, NAD.

NAD+ NADH

HSCoA

CO2

H3C
O

H3C
pyruvate dehydrogenase complex

pyruvate

2 per glucose (all of Krebs)

Oxidative decarboxylation
Makes NADH
-33.4kJ

O
SCoA

acetyl CoA

O
TAG's

H3C

SCoA

Kreb's

acetyl CoA

no CHO present

ketone bodies

CO2, ATP, NADH...energy

acetyl CoA
SCoA
H3 C
C

O
O

O
fumarase

C
C
H
O

C
O

C
C

NADH
C
NAD
HC OH
CH2
malate

H2O

dehydrogenase

H2O

citrate synthase

HO

Kreb's Cycle

FAD
O

C
CH2

CH2
C

O
O
succinate

GTP

SCoA

CoASH
GDP

succinyl CoA
synthetase

NADH

C
CH2
CH2
C
CO2
O

succinyl CoA

NAD

alpha ketoglutarate
O
O

C
NADH
C O CO2
CH2
CH2

CoASH

alpha ketoglutarate
dehydrogenase

C
CH O
HC C O
CH2
isocitrate
C

HO

dehydrogenase

aconitase

FADH2

succinate

C
CH2 O
C C O
CH2
citrate
C

oxaloacetate

malate

fumarate
O

C
C O
CH2
C
O

CoASH

NAD

isocitrate dehydrogenase

Oxidative process
3 NADH
FADH2
GTP

X 2 per glucose
6 NADH
2 FADH2
2 GTP

All ultimately turned into ATP (oxidative

phosphorylationlater)

H3C

SCoA

acetyl CoA

C
C O
CH2
C
O

H2O

CoASH
HO

citrate synthase
O

C
CH2
C C
CH2
C
O

oxaloacetate

citrate

O
O

HO

C
CH2 O
C C O
CH2
C
O

citrate

O
HO

aconitase

C
CH
HC C
CH2
C
O

O
O

isocitrate

O
HO

C
CH
HC C
CH2
C
O

O
O

NAD

NADH

CO2

isocitrate

C
C O
CH2
CH2
C

isocitrate dehydrogenase

alpha ketoglutarate

C
C O
CH2
CH2

SCoA

CoASH

CO2

NAD

NADH

C
O

alpha ketoglutarate

alpha ketoglutarate

C
CH2
CH2
C
O

dehydrogenase
succinyl CoA

SCoA

C
CH2
CH2
C
O

succinyl CoA

O
GDP

GTP

C
CH2

CoASH

CH2
succinyl CoA
synthetase

succinate

C
CH2

CH2
C
O
O
succinate

FAD

C
C

FADH2
H

succinyl CoA
dehydrogenase

C
C

fumarate

C
C
H
O

C
C

H2O
H
fumarase

fumarate

O
C
HC OH
CH2
C
O

malate

O
C
HC OH
CH2
C
O

malate

O
NADH

NAD

malate

dehydrogenase

C
C O
CH2
C
O

oxaloacetate

Oxidative process
3 NADH
FADH2
GTP

X 2 per glucose
6 NADH
2 FADH2
2 GTP

All ultimately turned into ATP (oxidative

phosphorylationlater)

Cytosol
Glycolysis
2 NADH
2 ATP

Mitochondrion
Pyruvate dehydrogenase
2 NADH

Krebs
6 NADH
2 FADH2
2 GTP

In mitochondrion:
Each NADH makes 2.5 ATP
Each FADH2 makes 1.5 ATP
GTP makes ATP

So
From in mitochondrion

8 NADH X 2.5 ATP/NADH = 20 ATP

2 FADH2 X 1.5 ATP/FADH2= 3 ATP
2 GTP X 1 ATP / GTP = 2 ATP
TOTAL in mitochondrion
25 ATP

Cytosol
2 ATP
2 NADH

NADH cant get into mitochondrion

In eukaryotes two pathways,

transferred to FADH2
get 1.5 ATP/ FADH2
Or transferred to NADH
Get 2.5 ATP/ NADH
(Not a problem in prokaryotes (why?))

2 NADH X 1.5 ATP

Or 2 NADH X 2.5 ATP
+
Total

= 3 ATP
= 5 ATP

=2 ATP
3+ 2 or 5 + 2 so either 5 or 7

Eukaryotes

Mitochondrial: 25 ATP
Cytosolic:
5 or 7 ATP
Total
30 or 32 ATP/glucose
30 ATP X 7.3kcal X 4.18 kJ = 915 kJ
ATP
If 32 ATP

kcal
=

976 kJ

Prokaryotes
32 ATP X 7.3kcal X 4.18 kJ = 976 kJ
ATP

kcal

Major hormones controlling fuel metabolism in mammals

Insulin
glucose uptake
glycolysis
hydrolysis
glycogen synthesis
glycogenolysis
triacylglycerol synthesis
protein, DNA, RNA synthesis

Glucagon
cAMP
glycogenolysis

inhibit
stimulate

cAMP
triacylglycerol

gluconeogenesis
triacylglycerol hydrolysis
glycogen synthesis

synthesis
gluconeogenesis
lipolysis
protein degredation

Epinephrine

glycolysis

glycogen

Major hormones controlling fuel metabolism in

mammals
Insulin:
> Synthesized in pancreas (islets of Langerhans, cells) in response to
high blood glucose.
> Signals the fed state.
> 5.8 kDa protein, cut from a larger precursor.

Glucagon:
> Synthesized in pancreas (islets of Langerhans, cells) in response to
low blood glucose.
> Signals glucose limitation.
> Primary target liver and adipose tissue.
> 3.5 kDa protein, cut from larger precursor.

Epinephrine: Catecholamine.
When released from presynaptic nerve endings, serves as
neurotransmitter.
When released from adrenal medulla, acts as hormone. Signals
glucose limitation.
Main targets muscle and adapose tissue.
Inhibits insulin secretion and stimulates glucagon secretion.

Thankyou