Table of Glycogen Storage Diseases Type: Name

GSD0a von Gierke GSD1a GSD1b GSD1c Pompe GSD2 Cori or Forbes GSD3

Enzyme Affected
glycogen synthase-2 glucose-6-phosphatase microsomal glucose-6phosphate translocase microsomal Pi transporter lysosomal acid -glucosidase also called acid maltase liver and muscle debranching enzyme branching enzyme muscle phosphorylase liver phosphorylase muscle PFK-1 phosphorylase kinase -subunit of PK glucose transporter-2 (GLUT-2)

Primary Organ
liver liver liver liver skeletal and cardiac muscle liver, skeletal and cardiac muscle liver, muscle skeletal muscle liver muscle, RBC's liver, leukocytes, muscle liver

Manifestations
hypoglycemia, early death, hyperketonia hepatomegaly, kidney failure, thrombocyte dysfunction like Ia, also neutropenia, bacterial infections like Ia infantile form = death by 2 juvenile form = myopathy adult form = muscular dystrophy-like infant hepatomegaly, myopathy hepatosplenomegaly, cirrhosis excercise-induced cramps and pain, myoglobinuria hepatomegaly, mild hypoglycemia, hyperlipidemia and ketosis, improvement with age like V, also hemolytic anemia

Andersen GSD4
McArdle GSD5 Hers GSD6 Tarui GSD7 GSD9a GSD9b Fanconi-Bickel hepatorenal glycogenosis

like VI
failure to thrive, hepatomegaly, rickets, proximal renal tubular dysfunction

The malate/aspartate shuttle

The malate/aspartate shuttle is the principal mechanism for the movement of reducing equivalents (in the form of NADH) from the cytoplasm to the mitochondria. The glycolytic pathway is a primary source of NADH. Within the mitochodria the electrons of NADH can be coupled to ATP production during the process of oxidative phosphorylation. The electrons are "carried" into the mitochondria in the form of malate. Cytoplasmic malate dehydrogenase (MDH) reduces oxaloacetate (OAA) to malate while oxidizing NADH to NAD+. Malate then enters the mitochondria where the reverse reaction is carried out by mitochondrial MDH. Movement of mitochondrial OAA to the cytoplasm to maintain this cycle requires it be transaminated to aspartate (Asp, D) with the amino group being donated by glutamate (Glu, E). The Asp then leaves the mitochondria and enters the cytoplasm. The deamination of glutamate generates -ketoglutarate (-KG) which leaves the mitochondria for the cytoplasm. All the participants in the cycle are present in the proper cellular compartment for the shuttle to function due to concentration dependent movement. When the energy level of the cell rises the rate of mitochondrial oxidation of NADH to NAD+ declines and therefore, the shuttle slows. G3PDH is glyceraldehyde-3-phosphate dehydrogenase.

glycerol phosphate shuttle

The glycerol phosphate shuttle is a secondary mechanism for the transport of electrons from cytosolic NADH to mitochondrial carriers of the oxidative phosphorylation pathway. The primary cytoplasmic NADH electron shuttle is the malate-aspartate shuttle. Two enzymes are involved in this shuttle. One is the cytosolic version of the enzyme glycerol-3-phosphate dehydrogenase (glycerol-3-PDH) which has as one substrate, NADH. The second is is the mitochondrial form of the enzyme which has as one of its' substrates, FAD+. The net result is that there is a continual conversion of the glycolytic intermediate, DHAP and glycerol-3-phosphate with the concomitant transfer of the electrons from reduced cytosolic NADH to mitochondrial oxidized FAD+. Since the electrons from mitochondrial FADH2 feed into the oxidative phosphorylation pathway at coenzyme Q (as opposed to NADH-ubiquinone oxidoreductase [complex I]) only 2 moles of ATP will be generated from glycolysis. G3PDH is glyceraldehyde-3-phoshate dehydrogenase.