Carbohydrates 4 Flashcards
Glycogen Synthesis Location
Occurs in muscle AND liver tissue–liver stores for whole body, muscle stores for itself–occurs in cytosol of cells
Steps of Glycogen Synthesis
- Glucose –> G-6-P (Hexokinase)
- G-6-P –> G-1-P (Phosphoglucomutase)
- G-1-P activated by binding to UDP (UDP-glucose pyrophosphorylase)
- Addition of glucose subunits to glycogenin (protein primer which gives short glucose chains)
- Once 7-8 glucose units attached glycogen synthase transfers glucose from UDP-glucose to the non-reducing end (alpha 1,4 bonds)
- Branching enzyme then cleaves off short fragment and attaches it to C6 of another chain giving alpha 1,6 bonds
Alpha(1,4) linkages
causes glucose to not be as reactive as free glucose
Glycogen degradation
glucose-phosphate is released from debranched chains of alpha(1,4) linked glucoses; alpha(1,4) glycosidic bonds replaced by a phosphate (glycogen phosphorylase) in order to conserve/utilize high energy from that bond and so it is released from non-reducing end as G-1-P; once degrading chain becomes too short debranching enzyme must further degrade glycogen since glycogen phosphorylase CANNOT work well close to alpha(1,6) linkages
Regulation of Hexokinase in Glycogen Synthesis
Inhibited by end product (G-6-P)
Stimulated by Insulin
Regulation of Glucokinase in Glycogen Synthesis
liver isozyme of hexokinase;
NOT inhibited by G-6-P—different from hexokinase
Stimulated by insulin
Regulation of Glycogen Synthase in Glycogen Synthesis
Inhibited by: Glucagon, Epinephrine
Stimulated by: Insulin
Regulation of Glycogen Phosphorylase in Glycogen Degradation
inhibited by: insulin
stimulated by glucagon and epinephrine
Regulation of Glucose-6-Phosphatase in Glycogen Degradation
inhibited by insulin
stimulated by glucagon and epinephrine
SAME enzyme as in GNG and SAME regulation
Glucagon Receptors
NOT found in muscle cells –only in liver cells
Glucagon Induced Phosphorylation activates and inactivates what?
Activates: Glycogen Phosphorylase
Inactivates: Glycogen Synthase
Insulin Induced Phosphorylation activates and inactivates what?
Activates: Glycogen Synthase
Inactivates: Glycogen Phosphorylase
When Glucagon binds to a receptor
cAMP cascade activated which activates PKA by -P’d
active PKA phosphorylates glycogen phosphorylase so that it may break down glycogen–>G-6-P and it also phosphorylates glycogen synthase (inactivating it)
cAMP cascade also stimulates glucose-6-phosphatase which converts G-6-P to glucose and glucose is released into circulation
When insulin binds to a receptor
Causes 1. glycogen synthase to become active by De-P’ing
2. downregulates GNG
Active Glyogen synthase converts G-6-P to glycogen
Hyperglycemia from hormonal failure to regulate blood glucose levels
if prolonged can damage blood/renal vessels and cause dehydration leading to coma–osmotically draws water out of cells
ex. diabetes
Hypoglycemia
affects brain function
van Gierke Type I
defect in glucose-6-phosphatase; renders kidney and liver unable to export glucose; hypoglycemia and increase liver glycogen stores
Pompe Type II
deficiency of acid maltase (alpha-glucosidase) which is required for degradation of glycogen that slowly accumulates in lysosomes; over time the lysosomes fill w/ glycogen and destroys affected cells; death or cardic/respiratory failure
Cori Disease Type III
Defect in glycogen debranching enzyme; glycogen granules grow large b/c only non-branched, outer layers of deposits are degraded
Type VI or V (V=McArdle Disease)
Type V and VI have different presentations (V in muscle, VI in liver); defect in glycogen phosphorylase; renders muscle unable to use stores, leads to greater than normal store in muscles; during exercise they have intense cramps due to lack of metabolic energy
Alcohol Metabolism (Main Pathway)
Ethanol –> Acetaldehyde (alcohol dehydrogenase; gives NADH)
Acetaldehyde –> Acetate (Acetaldehyde Dehydrogenase; gives NADH)
Acetate –> Acetyl-CoA (Thiokinase)
Acetyl-CoA CANNOT enter CAC because it is inhibited due to build up of NADH that inhibits citrate synthase, isocitrate dehydrogenase and alpha-KG dehydrogenase
instead acetyl-CoA produced will go to FA biosynthesis which can lead to fatty liver disease
Alcohol Metabolism (MEOS Pathway)
Ethanol–>Acetaldehyde (Microsomal Ethanol Oxidizing System); cytochrome p450 system which is induced by heavy alcohol consumption; takes NADPH and O2 –> NADP and 2H2O therefore weakens the cellular antioxidant defense mechanisms
Harmful effects of alcohol metabolism
production of high levels of NADH in cytoplasm reduces the capacity for GNG (watch for hypoglycemia/lactic acidosis) and blocks CAC (watch for ketoacidosis/accumulation of FA’s)
