Thom4/5-Gluconeogenesis, glycoproteins Flashcards
How is fructose metabolized?
- By phosphorylation at the one-position (with fructokinase)
- Then, conversion to intermediates of the glycolytic pathway (with aldolase)
- To F-6-P if [fructose] is very high
- Metabolized primarily in liver, but also in the small intestine and kidneys
What is Essential Fructosuria? :)
- It is a deficiency in fructokinase
- Benign; causes excessive fructose in the urine
What is Hereditary Fructose Intolerance?
- It is a deficiency in Fructose-1-P aldolase activity in aldolase B
- Severe hypoglycemia, liver & kidney damage
- Accumulation of F-1-P & Pi inadequate recycling cause a decrease in ATP & therefore an increase of glycolysis
- No gluconeogenesis because of low ATP
- Treated by limiting sweets
What happens if there is an excessive consumption of fructose?
–> There is sequestering of inorganic phosphate, & so there is inadequate regeneration of ATP
What is the significance of sorbitol in diabetes?
- Fructose can be synthesized from sorbitol (the sugar alcohol of glucose) in the seminal vesicle
- In the lens of the eye, elevated sorbitol levels in diabetes mellitus and galactitol (sugar alcohol of galactose) in galactosemia contribute to cataracts formation
What is classical galactosemia?
- Deficiency of galactose-1-P-uridylyltransferase (GALT)
- Accumulation of galactose-1-P in tissues
- Inhibition of glycogen metabolism and pathways that require UDP sugars
- Galactose in the blood and urine
What is non-classical galactosemia?
- Deficiency of galactokinase results in accumulation of galactose
- Galactose in diet comes from lactose
What are the symptoms in a baby with classical galactosemia?
–> Vomit, weigth loss, jaundice, liver enlargement, and cataracts
–> due to a deficiency of Galactose-1-P uridyltransferase
What are proteoglycans?
- A core protein covalently attached to many long, linear chains of glycosaminoglycans, which contain repeating disaccharide units
- Repeating disaccharides contain hexosamine and a uronic acid
How are proteoglycans synthesized?
1) Attachment of a sugar to a serine or threonine residue of core protein
2) Additional sugar add to non-reducing end (w/ UDP-sugars serving as precursor)
3) excreted from the cells & form EC matrix
What are the properties of glycosaminoglycans/Mucopolysaccharides/Proteoglycans?
–> Protein core with proteoglycan monomers are attached to hyaluronic acid backbone with a link protein
–> Important for normal joints: lubricates joints and surfaces that move along each other, such as cartilage
–>Examples: keratan and dermatan sulfate in cornea, heparin -an anticoagulant, chondroitin sulfate in bone and cartilage, heparan sulfate in skin fibroblasts & aortic wall, hylauronic acid in cell migration
What are some mucopolysaccharides diseases (lysosomal storage diseases)?
- Hurler’s syndrome & Scheie’s: degradation of dermatan & heparan sulfate bc of a-L-Iduronidase deficiency -> mental retardation, corneal clouding, dwarfing
- Sanfilippo’s syndrome: impaired removal of glucosamine residues -> severe nervous system disorders, mental retardation
- Hunter’s syndrome: Iduronate sulfate deficiency -> X-linked -> physical deformity & mental retardation*
- Sly’s syndrome: B-glucuronidase deficiency -> hepatosplenomegaly, physical deformity*
What are glycoproteins?
- Proteins with short chains of carbohydrates, usually branched (composed of glucose, galactose, & their amino derivatives)
- Mannose, L-fucose, & NANA frequently present
- Branched chains may be attached to the amide N of asparagine in the protein OR the O of serine side chain
What are some functions of glycoproteins?
1- Cell surface recognition
2- Cell surface antigenicity
3- Extracellular matrix
4- Mucins
What are the functions of glycolysis other than ATP production?
- > Provides carbon for FA synthesis in the liver
- > Production of glycerol-3-P, (combines with FAs to form triacylglycerols to be secreted in VLDL)
What is the difference between aerobic and anaerobic glycolysis?
1) Aerobic glycolysis: NADH produced goes through oxidative phosphorylation
2) Anaerobic glycolysis: NADH produced is used to convert pyruvate into lactate. NAD is regenerated through this reaction, allowing glycolysis.
What are the 2 bypass reactions in gluconeogenesis?
1) Pyruvate to Phosphoenolpyruvate: requires pyruvate carboxylase & PEP carboxykinase
2) F-1,6-bP to F-6-P: reverse the rate limiting step of glycolysis, hydrolysis catalyzed by F-1,6-bisphosphatase
3) G-6-P is converted to glucose: through the action of glucose-6-phosphatase
What is the Cori cycle?
- The reconversion of lactate to glucose by the liver
- Glucose produced in the liver by gluconeogenesis is converted in RBCs to lactate via glycolysis
- > Lactate returns ot liver & is reconverted to glucose by gluconeogenesis
What is the problem with excessive alcohol on an empty stomach?
–> ALcohol massively increases NADH concentration in liver:
pyruvate –> lactate, ethanol –> acetaldehyde, acetaldehyde—> acetate (all produce NADH)
—-> Intermediates of gluconeogenesis are diverted to other pathways –> decrease in glucose synthesis
What is disulfiram’s action?
- Used as part of a treatment plan for problem drinking
- Creates an unpleasant reaction when drinking alcohol
- Works by inhibiting the reaction of acetaldehyde to acetate by aldehyde dehydrogenase
How is glucose stored?
- As glycogen granules in the liver and in muscle
- It can be rapidly mobilized
What is Von Gierke disease (type I) ?
- Defective G-6-phosphatase or transport system (only in liver, normally releases glucose to blood)
- Affects the liver and kidney
- Increase glycogen storage
- Liver enlargement, hypoglycemia, ketosis, hyperuricemia, hyperlipemia, failure to thrive
What is Pompe disease (type II)?
- Defect in lysosomal a-1,4-glucosidase
- Affects all organs
- M_assive increase in glycogen amoun_t
- Cardiorespiratory failure, death before age 2
What is Cori disease (type III)?
- Defective amylo-1,6-glucosidase (debranching enzyme)
- Affects muscle and liver
- Increased amount of glycogen, short outer branches
- Like type I, but milder