Intermediary metabolism relationships

(saccharides, lipids, proteins)

1. after feeding (energy intake in a diet)

Intermediary metabolism

oxidation CO2, H2O, urea + ATP

formation of stores glycogen, TAG

Vladimra Kvasnicov

Urea

Intermediary metabolism relationships

(saccharides, lipids, proteins)
2. during fasting

use of energy stores

Glycogen

glycogen glucose

TAG fatty acids

formation of new energy substrates

nonreducing
end

reducing
end

The figures were found (May 2007) at http://www.wellesley.edu/Chemistry/chem227/sugars/oligo/glycogen.jpg

http://students.ou.edu/R/Ben.A.Rodriguez-1/glycogen.gif, http://fig.cox.miami.edu/~cmallery/255/255chem/mcb2.10.triacylglycerol.jpg

gluconeogenesis (glycerol, muscle proteins)

ketogenesis (storage TAG FFA ketone bodies)

The figure was adopted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed.
Wiley-Liss, Inc., New York, 1997. ISBN 0-471-15451-2

Principal metabolic pathways of the

intermediary metabolism:
glycogenesis

glycogenolysis

gluconeogenesis

glycolysis

lipogenesis

lipolysis

synthesis of FA

-oxidation

ketogenesis

ketone bodies degr.

proteosynthesis

proteolysis

urea synthesis

degradation of AA

CITRATE CYCLE, RESPIRATORY CHAIN

The figure was adopted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed.
Wiley-Liss, Inc., New York, 1997. ISBN 0-471-15451-2

Major intermediates

acetyl-CoA
pyruvate
NADH

pyruvate (PDH) i.e. from glucose

amino acids (degrad.) from proteins
fatty acids (-oxidation) from TAG
ketone bodies (degrad.) from FA

aerobic glycolysis
oxidation of lactate (LD)
degradation of some amino acids

pyruvate

acetyl-CoA

acetyl-CoA (PDH)
citrate cycle, RCH CO2, H2O, ATP
synthesis of FA
synthesis of ketone bodies
synthesis of cholesterol
synthesis of glucose !!!

lactate (lactate dehydrogenase)

alanine (alanine aminotransferase)
oxaloacetate (pyruvate carboxylase)
glucose (gluconeogenesis)

aerobic glycolysis
PDH reaction
-oxidation
citrate cycle
oxidation of ethanol

The most important is to answer the

questions:

NADH

HOW?

pyruvate lactate

respiratory chain reoxidation to NAD+

energy storage in ATP
! OXYGEN SUPPLY IS NECESSARY!

WHERE?
WHEN?

compartmentalization of the pathways

starve-feed cycle

regulation of the processes

1. Compartmentalization of mtb pathways

2. Starve-feed cycle
relationships of the metabolic pathways
under various conditions
cooperation of various tissues
see also
http://www2.eur.nl/fgg/ow/coo/bioch/#english
(Metabolic Interrelationships)

The figure is found at http://fig.cox.miami.edu/~cmallery/150/proceuc/c7x7metazoan.jpg (May 2007)

1) Well-fed state
The figure was adopted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed.
Wiley-Liss, Inc., New York, 1997. ISBN 0-471-15451-2

2) Early fasting state

The figure was adopted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed.
Wiley-Liss, Inc., New York, 1997. ISBN 0-471-15451-2

3) Fasting state
The figure was adopted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed.
Wiley-Liss, Inc., New York, 1997. ISBN 0-471-15451-2

4) Early refed state

The figure was adopted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed.
Wiley-Liss, Inc., New York, 1997. ISBN 0-471-15451-2

Changes of liver glycogen content

The figure was adopted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed.
Wiley-Liss, Inc., New York, 1997. ISBN 0-471-15451-2

The figure was adopted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed.
Wiley-Liss, Inc., New York, 1997. ISBN 0-471-15451-2

WELL-FED STATE

FASTING
STATE

hormones

insulin

glucagon,
adrenaline, cortisol

response of
the body

glycemia
lipogenesis
proteosynthesis

glycemia
lipolysis
ketogenesis
proteolysis

from food

from stores
(glycogen)
gluconeogenesis

source of
glucose
fate of
glucose

glycolysis
formation of stores

glycolysis

WELL-FED STATE

FASTING
STATE

source of
fatty acids

from food TAG

from storage TAG

fate of
fatty acids

-oxidation
synthesis of TAG

-oxidation
ketogenesis

source of
amino acids

from food

from muscle
proteins

fate of
amino acids

proteosynthesis
oxidation
lipogenesis

gluconeogenesis

enterocyte:

Gln citrulline blood kidneys

kidneys:

citrulline Arg blood liver

liver:

Arg urea + ornithine

Metabolism of ammonia
- the importance of glutamine synthesis of nucleotides ( nucleic acids)
detoxification of amino N (-NH2 transport)
synthesis of citrulline (used in urea cycle):
intake of proteins in a diet (fed state)

or

degradation of body proteins (starvation)

ornithine increased velocity of the UREA CYCLE

concentration of glutamine

= detoxification of NH3 from degrad. of prot.

3. General Principles of Regulation

catabolic / anabolic processes

last step of each regulation mechanism:

change of a concentration of an active
enzyme (= regulatory or key enzyme)

1.

signal transmission among cells

(signal substances)

2. signal transsduction through the cell membrane

regulatory enzymes

often allosteric enzymes

catalyze higly exergonic reactions
(irreverzible)

low concentration within a cell

II. Regulation on the cell level

1.

I. Regulation on the organism level

compartmentalization of mtb pathways

2. change of enzyme concentration

(on the level of synthesis of new enzyme )
3. change of enzyme activity
(an existing enzyme is activated or
inactivated)

3. influence of enzyme activity:

induction of a gene expression

interconversion of existing enzymes
(phosphorylation / dephosphorylation)

1. Compartmentalization of mtb patways

transport processes between compartments
various enzyme distribution
various distribution of substrates and
products ( transport)
transport of coenzymes
subsequent processes are close to each other

2. Synthesis of new enzyme molecules:

induction by substrate or repression by product
(on the level of transcription)

3. Change of activity of an existing enzyme

a) in relation to an enzyme kinetics

concentration of substrates (<
< Km)

examples:

xenobiotics induction of cyt P450

heme repression of delta-aminolevulate synthase

3. Change of activity of an existing enzyme

availability of coenzymes

consumption of products

pH changes

substrate specificity - different Km

Phosphorylation / dephosphorylation

b) activation or inactivation of the enzyme

some enzymes are active in a phosphorylated

form, some are inactive

phosphorylation:

covalent modification of the enzymes

interconversion: phosphorylation/dephosphorylation)

protein kinases

cleavage of an precursore (proenzyme, zymogen)

macroergic phosphate as a donor of the phosphate

(ATP!)

modulation of activity by modulators (ligands):

feed back inhibition

dephosphorylation

cross regulation

protein phosphatase

feed forward activation

inorganic phosphate is the product!

Reversible covalent
modification:

Modulators of enzyme activity

(activators, inhibitors)

A)
phosphorylation by
a protein kinase
dephosphorylation by
a protein phosphatase
B)
phosphorylated enzyme
is either active or
inactive
(different enzymes are
influenced differently)
The figure is found at: http://stallion.abac.peachnet.edu/sm/kmccrae/BIOL2050/Ch1-13/JpegArt113/05jpeg/05_jpeg_HTML/index.htm (December 2006)

isosteric modulation: competitive inhibition

allosteric modulation:

change of Km or Vmax

T-form (less active) or R-form (more active)

important modulators: ATP / ADP