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LDH isoenzymes:
How are they produced?

LDH: lactate dehydrogenase; EC 1.1.1.27 ; (S)-lactate:NAD oxidoreductase
Reversibly catalyses the reaction (S)-lactate + NAD flecha de equilibrio pyruvate + NADH + H+

Genes

There are two genes that code for subunits composing LDH. In humans, they are named LDHA gene and LDHB gene.

LDHA gene

Located in chromosome 11, locus 11p15.1

LDHB gene

Located in chromosome 12, locus 12p12.1


transcription + translation


transcription + translation
polypeptide chain "A" or "M"
polypeptide chain "B" or "H"

Proteins

Both polypeptides, "A" or "M" and "B" or "H", are very much alike in their structure, but they have some differences in their sequence:

Black background marks amino acid residues that match; ochre background, similar amino acids; white background, residues which are different.

As a consequence, their physicochemical properties are a little different, among them the isoelectric point and the electric charge.

The LDH enzyme is active as a tetramer: it is formed by 4 subunits, which may be either M or H type. It is, hence, possible for them to associate in 5 different combinations:

M4
M3H
M2H2
MH3
H4

which constitute the 5 isoenzymes of LDH.

Depending on one cell expressing in a higher or lower degree each one of the two genes, different relative amounts of the A and B polypeptides will be synthesised, and so the relative abundance of the 5 isoenzymes will be different.

You can try changing the relative expression of the LDHA and LDHB genes (by sliding the control) and observe the result:

higher expression of LDHA
higher expression of LDHB
Amounts of each isoenzyme:
M4
M3H
M2H2
MH3
H4

Examples:

In and the LDHA gene is predominantly expressed, which codes for subunit M.
In the LDHB gene is predominantly expressed, which codes for subunit H.
In both genes LDHA and LDHB are equally expressed.

Angel Herráez. Part of the Biomodel.uah.es website
Animated images were produced with Jmol in Proteopedia (2FM3.pdb)
Sequences were obtained from UniProtKB; alignment was computed at T-Coffee and plotted using BoxShade (ExPASy)