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Flashcards in Week 2 Deck (24):

pathway of glycogenesis

- conversion of glucose to glucose-6-phosphate through hexokinase (glucokinase)--G6p to G1P through posphoglucomutase--G1P to uridine diphosphoglucose-- highly branched, large polymer is then built by linking glucose molecules together by α-1,4-glucoside bonds. The glycogen chain and branches continue to be elongated by the addition of glucose molecules mediated by glycogen synthetases.


pathway of glycogenolysis

-phosphorylases split glucose-1-phosphate from the glycogen until about four glucose residues remain on each branch, leaving a branched oligosaccharide called limit dextrin. This can be further degraded only by the debranching enzyme. In addition to these major pathways, glycogen is also degraded in the lysosomes by acid maltase


regulation of glycogen metabolism in liver

-contains enzymes that synthesize glycogen for storage and ultimately break it down into free glucose
-inherited deficiency of hepatic enzymes that are involved in glycogen degradation leads to decrease in storage of glycogen and reduction in blood glucose concentrations


regulation of glycogen metabolism in skeletal and cardiac muscles

- glycogen is used predominantly as a source of energy during physical activity. ATP is generated by glycolysis, which leads ultimately to the formation of lactate
-If the enzymes that fuel the glycolytic pathway are deficient, glycogen storage occurs in the muscles and is associated with muscular weakness due to impaired energy productio


-clinical presentation

-muscle phosphorylase
-skeletal muscle only; accumulation of glycogen in sarcolemmal location
-painful cramps with strenuous exercise, myoglobinuria, onset in adulthood


-clinical presentation

-accumulation of glycogen in liver
-hepatomegaly, hypoglycemia, hyperlipidemia,


-clinical presentation

-liver phosphorylase
-hepatomegaly and slow growth that improve with age and disappear slowly
-hypoglycemia, hyperlipidemia, hyperketosis


Pompe disease
-clinical presentation

-lysomal glucosidase
-liver: ballooning of lysosomes with glycogen creatin lacy cytoplasmic pattern; heart and skeletal: glycogen within sarcoplasm
-mild hepatomegaly, cardiomegaly, muscle hypotonia, cardiorespiratory failure before age 2


mechanism for elevated serum creatine kinase with muscle dysfunction

-when muscle is damaged, it releases creatine kinase into the blood. Elevated levels of serum creatine kinase could be an indication for Pompe disease.


spectrum and progression of clinical presentation of Pompe disease

- autosomal recessively inherited deficiency of the glycolytic lysosomal enzyme α-glucosidase (formerly known as acid maltase) that cleaves the α-1,4 and α-1,6 glycosidic linkages
- infantile form is a severe generalized myopathy and cardiomyopathy. Patients have cardiomegaly and hepatomegaly and are diffusely hypotonic and weak. The serum CK level is greatly elevated. Death in infancy or early childhood is usual; however, enzyme replacement therapy has improved the outcome.
-late childhood or adult form is a much milder myopathy without cardiac or hepatic enlargement. It might not become clinically expressed until later childhood or early adult life but may be symptomatic as myopathic weakness and hypotonia even in early infancy


process and benefits of using a typical newborn blood spot screening panel

Texas law requires these laboratory tests to help find infants who may have one of the 53 conditions. The test requires a hearing screen and a simple heel stick blood sample collected from newborns shortly after birth and another at one to two weeks of age. If the laboratory test detects an infant with an abnormal result, the NBS Program's Clinical Care Coordination team initiates the process of follow-up with a health care provider for confirmatory testing. If it is determined your child has a condition, treatment will begin immediately.
Early detection of these 53 disorders allows early treatment that can prevent serious complications and the faster treatment begins, the greater chances your child will live a healthy life.



-lipoprotein found in blood that consists of protien, cholesterol, and triglyceride
-carry cholesterol and triglycerides in blood stream
-has more cholesterol



-lipoprotein found in blood that consists of protien, cholesterol, and triglyceride
-carry cholesterol and triglycerides in blood stream
-has more triglyceride


how defects in cholesterol biosynthesis and utilization contribute to the pathogenesis of familial hypercholesterolemia

-change in number of LDL receptors directly affects serum cholesterol levels.
-If liver does not take up LDL particles, serum LDLc levels increase and when LDL is not internalized by hepatocytes, hepatic synthesis of cholesterol is not suppressed which leads to further cholesterol production despite high levels of circulating cholesterol. .


Allelic heterogeneity

different mutations in gene produce same phenotype


Locus heterogeneity

mutations in different genes cause same phenotype



-If LDLR is mutated will not bring in LDL to cell
-LDL receptor gene located on short arm of chromosome 19; autosomal dominant mutation, worse with homo



-is a ligand on LDL that helps it bind to LDLR, if genetic mutation occurs then LDL cannot bind
-autosomal dominant; can be hetero or homo, worse with homo


Five classes of mutations on LDLR

Five classes of mutations:
• Class 1 includes null alleles that result in complete absence of the LDL receptor.
• Class 2 includes defective transport alleles, which disrupt normal folding of receptor and cause either failure in transport to cell surface or successful transport of truncated, mutated receptors.
• Class 3 includes defective binding alleles that affect binding of LDL
• Class 4 includes defective internalization alleles that affect concentration of normal receptors in clathrin-coated pits for internalization by hepatocyte.
• Class 5 includes defective recycling alleles that prevent dissociation of receptor and ligand and interrupt recycling of receptor.


Difference between hetero and homozygous FH

Homo: severely elevated cholesterol levels (total and LDL > 600)
Hetero: Elevated LDL, usually greater than 250



- irregular yellow patch or nodule on the skin, caused by deposition of lipids.
-tendonxanthomas, cutaneous (palms, soles)


Specific labs and genetic tests used to diagnose FH

-Total cholesterol
-cascade screening
-family history of early CVD/MI



selectively and competitively inhibits the hepatic enzyme HMG-CoA reductase. As HMG-CoA reductase is responsible for converting HMG-CoA to mevalonate in the cholesterol biosynthesis pathway, this results in a subsequent decrease in hepatic cholesterol levels. Decreased hepatic cholesterol levels stimulates upregulation of hepatic LDL-C receptors which increases hepatic uptake of LDL-C and reduces serum LDL-C concentrations.



Blood from patient is passed into machine that filters plasma, platelets, and whole blood. Excess LDL will be filtered from plasma