GLUT 3
neurons
Km = 1
basal transport
GLUT 1
most tissues, RBCs, BBB
Km = 5
basal transport
GLUT 2
liver, kidney, pancreatic B cells, & basolateral side of brush border of intestine
Km = 15, low affinity transport
V max = higher
levels induced by insulin - ensures blood glucose equilibrates rapidly across hepatocyte membrane
GLUT 4
muscle, adipose
number + activity influenced by insulin
Km = 5
MAJOR INSULIN RESPONSIVE TRANSPORTER
GLUT 5
apical brush border, sperm, testes (fructose-metabolizing tissues)
specific for FRUCTOSE
SGLT 1
apical brush border, renal tubules, choroid plexus
3 Regulatory Enzymes of Glyolysis
- Hexokinase
- Phosphofructokinase = PFK1
- Pyruvate Kinase = PK
Hexokinase I-III
- broad substrate specifity
- inhibited by G6P
- low Km
- permits phosphorylation & metabolism even when tissue glucose is LOW
- Low Vmax
Hexokinase IV - Glucokinase
- liver and B cells of pancreas
- glucose sensor in B cells, determines threshold for insulin secretion
- insulin-sensitive - upregulates transcription of glucokinase mRNA
- HIGH Km - only when glucose is elevated
- HIGH Vmax
McArdle Disease (GSD 5)
- Autosomal recessive
- Deficiency in skeletal muscle glycogen phosphorylase (liver normal)
- Onset in early adulthood
- Intolerance to exercise, chronic muscle cramps (can’t break down glycogen for energy in muscle )
- Transient myoglobinemia and myoglobinuria following exercise due to rhabdomyolysis, and renal failure with severe myoglobinuria
- Serum glucose regulation is normal
- Benign with progressive muscle weakness and atrophy with fatty replacement
Her’s Disease (6)
Autosomal recessive
Defect in liver glycogen phosphorylase
Mild to moderate hypoglycemia, mild ketosis, and prominent hepatomegaly
Muscle & heart unaffected
Good prognosis
Distinguished from GSD VIII which is X-Linked defect in glycogen phosphorylase kinase
Cori (Forbes) Disease 3
Autosomal recessive
Defect in liver glycogen phosphorylase
Mild to moderate hypoglycemia, mild ketosis, and prominent hepatomegaly
Muscle & heart unaffected
Good prognosis
Distinguished from GSD VIII which is X-Linked defect in glycogen phosphorylase kinase
Pompe Disease 2
Autosomal recessive, rare (5-10,000 US cases)
Lysosomal storage disease resulting from defect in α(1-4) glucosidase
Lysosome takes up glycogen molecules and cannot break them down
Adolescent & Adult Onset
Skeletal myopathy
Serum glucose regulation is normal except in severe liver damage
Infantile Pompe (Classic) 2
Infantile onset (classic Pompe)
Cardiomyopathy and muscle hypotonia are primary presentations with children prostrate and listless
Experimental Enzyme Replacement Therapy for Early Onset Pompe’s disease
ERT relies on a recombinant form of human α(1-4) glucosidase modified with mannose-6-phosphate groups to facilitate phagocytic uptake of the enzyme into the lysosomes
Von Gierke (I)
Glucose-6-Phosphatase deficiency (type Ia)
Glucose-6-Phosphate Translocase deficiency (type Ib)
Glucose export from the liver is regulated in part by subcellular localization. G-6-Phosphatase exists in ER lumen, consequently, cytoplasmic G-6-P must be transported into the lumen by glucose-6-phosphate translocase
Severe hypoglycemia following exercise or short-term fast
Lipidemia results from shunting of excess G6P to triglyceride synthesis
Childhood mortality was common, now good prognosis for surviving to adulthood
Elevated G6P results in progressive liver glycogen deposition due to allosteric inhibition of glycogen phosphorylase
