Introduction
GAPDH is an acronym, which in full is “glyceraldehyde-3-phosphate dehydrogenase” (Mozdziak, Dibner and McCoy, 2003, p. 438). Just as it is indicated in the full name of GAPDH, it is an enzyme that is responsible for the catalysis process, which takes place in the sixth step of glycolysis (breakdown of glucose). This, therefore, means that GAPDH speeds up the conversion of glyceraldehyde-3-phosphate during the breakdown of glucose hence a glycolytic enzyme. This catalytic process takes place in the presence of NAD (nicotinamide adenine dinucleotide) and inorganic phosphate. From this description, it can be depicted that GAPDH is an essential enzyme when it comes to the processes/ pathways of glycolysis and gluconeogenesis.
Role in metabolic pathways
In addition to the major roles in metabolic pathways, GAPDH plays other critical roles such as initiating signals during cellular apoptosis and in diabetic retinopathy development among other functions. Recently, GAPDH has been described as a “regulator of cell death” (Barber, R. et al, 2005, p.390). Nevertheless, its contribution to cell death is uncertain, though some researchers have linked it to a proapoptotic function. Research done on GAPDH indicated that it has the potential of having macromolecules bound in cells. It binds with the voltage-dependent anion channel (VDAC) hence encouraging the release of cytochrome C (Cyt C) and apoptotic cell death.
GAPDH acts as a catalyst in the sixth step of glycolysis, which involves the conversion of glyceraldehyde- 3-phosphate into D-glycerate1, 3-biphosphate. In addition, free energy is released and is used in the formation of high-energy compounds ATP (Adenosine triphosphate) and NADH (reduced nicotinamide adenine dinucleotide). For glycolysis to occur “Cellular levels of NAD+ must be replenished for either from the reduction of pyruvate to lactate in anaerobic conditions or by electron transfer from NADH to O2 through the electron transport chain” (Mozdziak, Dibner, and McCoy, 2003, p. 440).
When subjected to oxidative stress, GAPDH undergoes reversible thiolation (-SSF). On the other hand, Oxidants can induce irreversible oxidation of cysteine residues, which “favor intermolecular disulfide bonds and formation of cytosolic aggregates of GAPDH” (Mozdziak, Dibner, and McCoy, 2003, p. 441). This is an insoluble protein and may result in cellular dysfunction or even cell death. NADPH is an antioxidant cofactor used in the inactivation of GAPDH. “The inactivation re-routes temporally the metabolic flux from glycolysis to the Pentose Phosphate Pathway, allowing the cell to generate more NADPH” (Tarze et al, 2007, p.2020).
Other roles in cells
Other roles performed by GAPDH include cytoskeleton and vesicular transport from the endoplasmic reticulum (ER) to the Golgi apparatus. It has been established that GAPDH interacts with tubulin, actin, hence enabling microtubule bundling and actin polymerization. Barber, R. et al. (2005) found out that GAPDH could ignite its transcription. “GAPDH moves between the cytosol and the nucleus and may thus link the metabolic state to gene transcription” (Barber, R. et al, 2005). GAPDH is also involved in the initiation of apoptosis.
Ways in which temperature influences enzymes in fermentation
Enzymes are larger organic catalysts that facilitate chemical reactions among them, fermentation. Enzymes normally work best under certain conditions optimum for their activity. For instance, fermentation occurs best at high temperatures. However, it has been noted that the ideal temperature for most enzymes is that close to the human body temperatures, normally referred to as warm. Enzymes responsible for fermentation participate in the series of reactions involved hence making them faster. As such, enzymes tend to be inactive in cold temperatures.
GAPDH genes in plants
The GAPDH genes in plants include NADP+-dependent enzyme, which is found within their chloroplasts and consists of which is two subunits, GapA and GapB. Recently, plastid GAPDH enzyme (GapCp) was discovered in gymnosperms, ferns, and displays glycolytic NAD+ cosubstrate specificity. This implies that it is also present in angiosperms, liverworts, and mosses “Phylogenetic analyses of the available GapC and GapCp sequences suggest that the gene duplication giving rise to GapCp occurred in ancestral charophyte algae” (Tarze et al, 2007, p.2015).In flowering plants, GapCp plays a specific role in the glycolytic energy production of nongreen plastids.
Isoforms (protein structures)
Short-chain lengths of amino acids are referred to as peptides while the longer chain lengths (with more than 30 amino acids) are known as proteins. Proteins perform various functions, including structural roles (cytoskeleton), as catalysts (enzymes), and a media for transporting ions and molecules across membranes. GAPDH is a type of protein as it contains a chain of 335 amino acids.
GAPDH consists of several Isoforms and each has a specific function. These isoforms include Voltage-gated LTCCs (L-type Ca2+ channels), Myosin, CD40, and Hsp90 isoforms. Voltage-gated LTCCs help in controlling synaptic plasticity in neurons and hence they modulate brain function. Hsp90 isoform is a kind of a heat shock protein and performs functions like apoptosis, cell proliferation, and differentiation. Myosin is known for its role in muscle contraction and its involvement in eukaryotic processes. All eukaryotic cells contain myosin isoforms.
There is a difference between GAPDH genes in plants and animals in that in animals, GAPDH is more of a housekeeping gene and in plants, it is used for energy production and in gene duplication. In plants, it’s located in the chloroplast and animals; it’s concentrated in tissues that require high energy demands especially in the skeletal muscle, left ventricle, and the brain regions (Mozdziak, Dibner & McCoy, 2003).
Conclusion
Information on GAPDH is quite important, as it is an essential enzyme in both plants and animals. As discussed in the essay, GAPDH plays a major role in various metabolic pathways such as cellular respiration, glycolysis, and aerobic and anaerobic pathways.
Reference List
Barber, R. et al. (2005). GAPDH as a housekeeping gene: analysis of GAPDH mRNA expression in a panel of 72 human tissues. Physiological Genomics, 21(3), 389–395.
Mozdziak, P., Dibner, J., and McCoy, W. (2003). Glyceraldehyde-3-phosphate dehydrogenase expression varies with age and nutrition status. Nutrition,19, 438–440.
Tarze, A. et al. (2007). GAPDH, a novel regulator of the pro-apoptotic mitochondrial membrane Permeabilization, Oncogene, 26(18), 2606–2620.