Liver glycogen storage

Inherited deficiencies in specific enzymes of glycogen metabolism in both liver and muscle are the causes of glycogen storage diseases. 

There are important methodologic considerations which apply to the use of cultured amniotic fluid cells for the detection of biochemical disorders. The first is that the enzymes which can be sampled are those which are usually present in fibroblasts or fibroblast-like cells. Therefore, conditions such as phenylketonuria and glycogen storage disease type I, which are associated with deficiencies of enzymes present only in liver and kidney, are not amenable to this approach. The same also pertains to enzyme deficiencies affecting other specific tissues. 

The most common glycogen storage disease. Type I or von Gierke disease, is a deficiency in glucose 6-phosphatase in which glycogen structures are normal however, the liver is unable to dephosphory-late glucose 6-phosphate, and it remains trapped In the cell. 

However, in some glycogen storage diseases (see p. 128), the amount of glycogen in the liver and/or muscle can be significantly higher. 

The release of glucose from the glycogen stores in the liver is mediated by glucose 6-phosphatase, which is apparently embedded within the membranes of the endoplasmic reticulum. A labile enzyme, it consists of a 357-residue catalytic subrmit,251/252 which may be associated with other subunits that participate in transport.252 253 A deficiency of this enzyme causes the very severe type la glycogen storage disease (see Box 20-D).251 253 Only hepatocytes have significant glucose 6-phosphatase activity. 

The main function of the liver s glucose sensing activities is to provide a switch that directs GNG towards glycogen storage or towards glucose release. Only occasionally, Jgk becomes so large that there is a transient net glucose uptake [37, 38]. 

The biological effect of (-)-HCA stems from the inhibition of extramitochondrial cleavage of citrate to oxaloacetate and acetyl-CoA catalysed by ATPicitrate lyase. This limits the availability of acetyl-CoA units required for fatty acid synthesis and lipogenesis (Sullivan, 1984). The inhibition of ATP cit-rate lyase by (-)-HCA leads to less dietary carbohydrate utilization for the synthesis of fatty acids, resulting in more glycogen storage in the liver and muscles. Many in vitro... 

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