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FIGURE 22–1 The nitrogen cycle.

BIOSINTESIS ASAM AMINO

Tumbuhan dan bakteri dapat mensintesis 20

asam amino yg umum

Mamalia dapat mensintesis sekitar separuhnya,

yang lainnya diperlukan di dalam diet (asam
amino essential)

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FIGURE 22–9
Overview of amino acid
biosynthesis

The carbon skeleton

precursors derive from three
sources:

• glycolysis (pink),
• the citric acid cycle (blue),
• the pentose phosphate
pathway (purple).

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Diantara asam amino nonesensial,

glutamate dibuat dg aminasi reduktif dari α-ketoglutarate dan mrpk

prekursor glutamine, proline, dan arginine.

Alanine dan aspartate (dan selanjutnya asparagine) dibentuk dari

pyruvate dan oxaloacetate, melalui transaminasi.

Rantai karbon dari serine dibuat dari 3-phosphoglycerate. Serine

adalah precursor glycine; atom karbon-β dari serine dipindahkan ke
tetrahydrofolate.

Pd mikroorganisme, cysteine dihasilkan dari serine dan dari sulfide

yg dibuat dg mereduksi sulfate dari lingkungan.

Mamalia membuat cysteine dari methionine dan serine melalui

serangkaian reaksi yg membutuhkan S-adenosylmethionine dan
cystathionine.

Diantara asam amino essential,

asam amino aromatik (phenylalanine, tyrosine, dan

tryptophan) dibentuk melalui jalur dimana chorismate mrpk titik
cabang kunci (key branch point).

Phosphoribosyl pyrophosphate adalah precursor dari

tryptophan dan histidine.
Jalur sintesis histidine saling behubungan dg jalur sintesis purine.

Tyrosine dpt juga dibuat melalui hidroksilasi phenylalanine (dan

krnnya dianggap esensial).

Jalur utk asam amino essential lainya adalah kompleks.

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Suatu cara bermanfaat untuk mengorganisir jalur2 biosynthetic ini dg

menggolongkannya ke dalam enam kelompok yg berhubungan
dengan prekursor metabolitnya (Tabel 22–1)

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A. Biosintesis Asam Amino Non-essensial

10 Asam Amino Non-essensial :

1. Alanin
2. Aspartat
3. Asparagin
4. Glisin
5. Sistein
6. Glutamat
7. Glutamin
8. Prolin
9. Serin
10. Tirosin

Asam amino
+
transaminasi Asam amino
Asam α-keto
aminotransferases nonesensial
 α-ketoglutarate
or transaminases
 oxaloacetate
 pyruvate

FIGURE 18–4 Enzyme-catalyzed transaminations.

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transaminasi
1. Piruvat Alanin
transaminasi
2. Oksaloasetat Aspartat
transaminasi
3. Aspartat Asparagin
transaminasi
4. α-ketoglutarat Glutamat
transaminasi
5. Glutamat Glutamin

6. Glutamat Prolin

7. 3-fosfogliserat fosfoserin Serin

fosfogliserat

8. Serin + tetrahidrofolat Glisin

kolin + betain

9. Homosistein + Serin Homoserin + Sistein

O2
10. Phe + tetrahidrobiopterin Tirosin +

dihidrobiopterin +

H2O

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B. Biosintesis Asam Amino Essensial

Hewan tingkat tinggi tdk mampu membuat bbrp asam

amino (asam amino esensial)
krn tdk memiliki satu atau dua enzim pd lintasan
sintesisnya

Lintasan biosintesis asam amino esensial :

• lebih panjang
5 s/d 15 tahap
• lebih kompleks

Lintasan biosintesis asam amino nonesensial :

< 5 tahap

5 asam amino esensial bagi hewan disintesis oleh

tanaman dan mikroorganisme dari asam amino yg
nonesensial

Treonin, metionin dan lisin dibentuk dari aspartat

Arginin dan histidin dibentuk dari glutamat

Isoleusin dibentuk dari asam amino esensial treonin

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Lintasan biosintesis asam amino esensial yg paling

kompleks adalah lintas menuju fenilalanin, triptofan dan
histidin, yg memiliki cincin benzen atau heterosiklik

Memerlukan sejumlah tahap reaksi enzimatik

yg kompleks

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Alanine and aspartate (and thus asparagine) are

formed from pyruvate and oxaloacetate, respectively,
by transamination.

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Alanine and aspartate are synthesized from pyruvate

and oxaloacetate, respectively, by transamination from
glutamate.

Asparagine is synthesized by amidation of aspartate, with

glutamine donating the NH4+.
These are nonessential amino acids, and their simple
biosynthetic pathways occur in all organisms.

Methionine, threonine, lysine, isoleucine, valine, and

leucine are essential amino acids. Their biosynthetic
pathways are complex and interconnected (Fig. 22–15).

In some cases, the pathways in bacteria, fungi, and

plants differ significantly.

Hal 846

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The pathway to histidine in all plants and bacteria differs

in several respects from other amino acid biosynthetic
pathways.

Histidine is derived from three precursors (Fig. 22–20):

• PRPP contributes five carbons,
• the purine ring of ATP contributes a nitrogen and a carbon,
• and glutamine supplies the second ring nitrogen.

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Aromatic rings are not readily available in the

environment, even though (walaupun) the
benzene ring is very stable.

The branched pathway to tryptophan, phenylalanine, and tyrosine,

occurring in bacteria, fungi, and plants, is the main biological route of aromatic ring
formation. It proceeds through ring closure of an aliphatic precursor followed by
stepwise addition of double bonds.

The first four steps produce shikimate, a seven-carbon molecule derived from
erythrose 4-phosphate and phosphoenolpyruvate (Fig. 22–16).

Shikimate is converted to chorismate in three steps that include the addition of three
more carbons from another molecule of phosphoenolpyruvate.

Chorismate is the first branch point of the pathway, with one branch leading to
tryptophan, the other to phenylalanine and tyrosine.

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Hal 848

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FIGURE 22–17 Biosynthesis of tryptophan

from chorismate in bacteria and plants.
In E. coli, enzymes catalyzing steps 1 and 2 are
subunits of a single complex.

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Glutamate is formed by reductive amination of α-ketoglutarate and

serves as the precursor of glutamine, proline, and arginine.

Glutamate is the source of amino groups for most

other amino acids, through transamination reactions
(the reverse of the reaction shown in Fig. 18–4).

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The biosynthetic pathways to glutamate and glutamine

are simple, and all or some of the steps occur in
most organisms. The most important pathway for the assimilation
of NH4+ into glutamate requires two reactions.
First, glutamine synthetase catalyzes the reaction of
glutamate and NH4+ to yield glutamine. This reaction
takes place in two steps, with enzyme-bound γ-glutamyl
phosphate as an intermediate (see Fig. 18–8):

Glutamine synthetase is found in all organisms. In addition

to its importance for NH4+ assimilation in bacteria,
it has a central role in amino acid metabolism in
mammals, converting toxic free NH4+ to glutamine for
transport in the blood (Chapter 18).

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FIGURE 18–8 Ammonia transport in the form of

glutamine. Excess ammonia in tissues is added to
glutamate to form glutamine, a process catalyzed by
glutamine synthetase. After transport in the bloodstream,
the glutamine enters the liver and NH4+ is liberated in
mitochondria by the enzyme glutaminase.

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FIGURE 22–10 Biosynthesis of proline and arginine from glutamate

in bacteria. All five carbon atoms of proline arise from glutamate. In
many organisms, glutamate dehydrogenase is unusual in that it uses
either NADH or NADPH as a cofactor. The same may be true of other
enzymes in these pathways. The γ-semialdehyde in the proline pathway
undergoes a rapid, reversible cyclization to Δ1-pyrroline-5-
carboxylate (P5C), with the equilibrium favoring P5C formation.
Cyclization is averted in the ornithine/arginine pathway by acetylation
of the -amino group of glutamate in the first step and removal of the
acetyl group after the transamination. Although some bacteria lack
arginase and thus the complete urea cycle, they can synthesize arginine
from ornithine in steps that parallel the mammalian urea cycle,
with citrulline and argininosuccinate as intermediates (see Fig. 18–10).
Here, and in subsequent figures in this chapter, the reaction arrows
indicate the linear path to the final products, without considering
the reversibility of individual steps. For example, the second step
of the pathway leading to arginine, catalyzed by N-acetylglutamate
dehydrogenase, is chemically similar to the glyceraldehyde 3-phosphate
dehydrogenase reaction in glycolysis (see Fig. 14–7) and is readily
reversible.

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The carbon chain of serine is derived from 3-

phosphoglycerate.

Serine is a precursor of glycine; the β-carbon atom of serine is

transferred to tetrahydrofolate.

In microorganisms, cysteine is produced from serine and from

sulfide produced by the reduction of environmental sulfate.
Mammals produce cysteine from methionine and serine by a
series of reactions requiring S-adenosylmethionine and
cystathionine.

Serine (three carbons) is the

precursor of glycine (two carbons)
through removal of a carbon atom by
serine hydroxymethyltransferase
(Fig. 22–12).

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