It is non-essential & glucogenic amino acid.

Cysteine is present in large quantity in

keratin of hair & nails.

Formation of cysteine is by using the carbon

skeleton contributed by serine & sulfur

originating from methionine.

Homocysteine formed from methionine is a

precursor for the synthesis of cysteine.

Homocysteine condenses with serine to form

cystathionine.

This reaction is catalysed by a PLP-

dependent cystathionine synthase.

The enzyme cystathioninase (PLP-dependent)

cleaves & deaminates cystathionine to

cysteine & α-ketobutyrate.

Methionine

Homocysteine

Cystathionine

Cysteine α-ketobutyrate

Serine

H2OCystathionine β-synthase

Succinyl CoA

γ-Cystathioninase

Homocysteinemiatype-1

Cysteine formation

Homocysteine is an intermediate in the synthesis of

cysteine from methionine.

Elevation in plasma homocysteine (normal <15 pmol/l)

has been implicated in coronary artery disease.

Homocysteine reacts with collagen to produce

reactive free radicals, besides interfering with

collagen cross links.

Homocysteine is also involved in the aggregation of

LDL particle & leads to atherosclerosis.

Cystine & cysteine are interconvertible by an

NAD+ dependent cystine reductase.

Cysteine on decarboxylation produces

mercaptoethanolamine which is involved in

the biosynthesis of coenzyme A from the

vitamin pantothenic acid.

Decarboxylation Cysteine

Decarboxylase, PLP

The enzyme cysteine dioxygenase oxidizes

cysteine to cysteine sulfinate, on further

oxidation, is converted to cysteic acid.

Cysteic acid undergoes decarboxylation to

produce taurine which conjugates with bile

acids.

Cysteic acid can also be degraded to

pyruvate, which is glycogenic.

Formation of taurine from cysteine

1. Cysteine dioxygenase, 2. Decarboxylase

Cysteine sulfinate cleaves off alanine to

produce sulfite which is converted to sulfate

& excreted in urine.

Some amount of sulfate condenses with ATP

to form active sulfate or 3'-

phosphoadenosine 5'-phosphosulfafe (PAPS).

Active sulfate (PAPS) is utilized for the

synthesis of mucopolysaccharides.

Used in detoxification.

Sulfate is also a structural component of

proteins & lipids.

Cysteine can be degraded by desulfhydrase to

liberate sulfur (as H2S), ammonia & pyruvate.

Cysteine is a component of glutathione.

PAPS

Cysteine is required for formation of

Glutathione.

Glutathionine is required for transport of

amino acids.

Glutathione is present in the RBCs.

This is used for inactivation of free radicals

formed inside RBC.

Glutathione helps to detoxify several

compounds.

Glutathione keeps the enzymes in reduced,

active state.

Cysteine residues in polypeptide chains form

disulfide bridges to make active proteins,

e.g. insulin & immunoglobulins.

Cystinuria (cystine-lysinuria):

The most common inherited disease.

It is characterized by increased excretion of

cystine (25-40 times normal).

Elevation in the urinary output of lysine,

arginine & ornithine is also observed.

A specific carrier system exists in kidney

tubules for the reabsorption of amino acids,

namely cysteine, ornithine, arginine & lysine

(COAL to recall).

In cystinuria, this carrier system becomes

defective leading to the excretion of all these

four amino acids in urine.

Cystine is relatively insoluble & increased

concentrations leads to precipitation &

formation of cystine stones in kidney & urinary

tract.

Cystinuria is usually identified in the

laboratory by cyanide nitroprusside test.

The treatment includes restricted ingestion of

dietary cystine & high intake of fluids.

Cystine crystals are deposited in many tissues

& organs of reticuloendothelial system

throughout the body.

These include spleen, lymph nodes, liver,

kidney, bone marrow etc.

A defect in the Iysosomal function.

Cystine accumulates in the lysosomes of

various tissues.

In cystinosis, renal function is impaired.

It is characterized by generalized amino

aciduria.

The affected patients die within 10 years,

mostly due to renal failure.

It is also due to defect in the enzyme cystine

reductase (interconverting enzyme).

Homocystinurias are a group of metabolic

disorders characterized by the accumulation

& increased urinary excretion of

homocysteine & S-adenosylmethionine (SAM).

Plasma concentration of methionine is

increased.

Enzyme defect: Cystathionine synthase.

Accumulation of homocystetne.

It results in various complications-thrombosis,

osteoporosis & mental retardation.

The deficiency of cystathionine is associated

with damage to endothelial cells which might

lead to atherosclerosis.

Two forms of type I homocystinurias

One of them can be corrected with vitamin B6

supplementation (B6 responsive) while the

other does not respond to B6.

The treatment includes consumption of diet

low in methionine & high in cystine.

The patients of homocystinuria have high

levels of homocysteine & usually die of

myocardial infarction, stroke.

Homocystinuria ll:

N5 - N10 - Methylene THF reductase.

Homocystinuria lll:

N5 - N10 - Methyl THF homocysteine methyltransferase.

This is mostly due to impairment in the synthesis of

methylcobalamin.

Homocystinurla lV:

N5 - Methyl THF homocysteine methyl transferase.

This is primarily due to a defect in the intestinal

absorption of vitamin B12.

Textbook of Biochemistry - U Satyanarayana

Textbook of Biochemistry - DM Vasudevan