823984 gluconeo-glycogen-metabolism
Post on 02-Nov-2014
982 Views
Preview:
DESCRIPTION
TRANSCRIPT
www.Examville.comOnline practice tests, live classes, tutoring, study guides
Q&A, premium content and more.
GLYCOGEN GLYCOGEN METABOLISMMETABOLISM
GLUCONEOGENESISGLUCONEOGENESIS
GLUCONEOGENESISGLUCONEOGENESIS synthesis of glucose from noncarbohydrate synthesis of glucose from noncarbohydrate
precursors during longer periods of precursors during longer periods of starvationstarvation a very important pathway since the brain a very important pathway since the brain depends on glucose as its primary fuel depends on glucose as its primary fuel ((120g 120g of of the 160g daily need for glucosethe 160g daily need for glucose)) and RBCs and RBCs use only use only glucose as fuelglucose as fuel amount of glucose in body fluids is 20g and amount of glucose in body fluids is 20g and
the the amount that can be derived from amount that can be derived from glycogen is glycogen is 190g190g major noncarbohydrate sources are major noncarbohydrate sources are lactatelactate, ,
amino acidsamino acids, and , and glycerolglycerol
noncarbohydrate sources need to be first noncarbohydrate sources need to be first converted to either converted to either
pyruvatepyruvate,,oxaloacetate oxaloacetate or or dihydroxyacetone phosphate (DHAP)dihydroxyacetone phosphate (DHAP)
to be converted to glucoseto be converted to glucose major site is the major site is the liverliver with small amount with small amount taking taking
place in the place in the kidneyskidneys gluconeogenesis in the liver and kidneys gluconeogenesis in the liver and kidneys
helps helps maintain the glucose demands of maintain the glucose demands of the the brain and brain and muscles by increasing muscles by increasing blood glucose blood glucose levelslevels
little occurs in the brain, skeletal muscle little occurs in the brain, skeletal muscle or or heart muscleheart muscle
not a reversal of glycolysisnot a reversal of glycolysis
NONCARBOHYDRATE SOURCESNONCARBOHYDRATE SOURCES PyruvatePyruvate is converted to glucose in the is converted to glucose in the
gluconeogenetic pathwaygluconeogenetic pathway
LactateLactate is formed by is formed by active skeletal muscleactive skeletal muscle when when glycolytic rate exceeds oxidative rate; becomes glycolytic rate exceeds oxidative rate; becomes glucose by first converting it to glucose by first converting it to pyruvatepyruvate
Amino acidsAmino acids are derived from are derived from dietary proteinsdietary proteins and and internal protein breakdowninternal protein breakdown during starvationduring starvation; ; becomes glucose by converting them first to either becomes glucose by converting them first to either pyruvate or oxaloacetatepyruvate or oxaloacetate
Glycerol Glycerol is derived from the is derived from the hydrolysis of hydrolysis of triacylglycerols (TAG) or triglyceridestriacylglycerols (TAG) or triglycerides; becomes ; becomes glucose by conversion first to glucose by conversion first to dihydroxyacetone dihydroxyacetone phosphate (DHAP)phosphate (DHAP)
IRREVERSIBLE STEPS of GLYCOLYSISIRREVERSIBLE STEPS of GLYCOLYSISCauses of most of the decrease in free energy Causes of most of the decrease in free energy
in glycolysisin glycolysis
Bypassed steps during gluconeogenesisBypassed steps during gluconeogenesis
Steps catalyzed by the enzymesSteps catalyzed by the enzymesHexokinase Hexokinase
((glucose + ATP glucose + ATP G-6-P + ADP G-6-P + ADP))Phosphofructokinase Phosphofructokinase
((F-6-P + ATP F-6-P + ATP F-1,6-BP + ADP F-1,6-BP + ADP))Pyruvate kinasePyruvate kinase
((PEP + ADP PEP + ADP Pyruvate + ATP Pyruvate + ATP))
NEW STEPS in GLUCOSE FORMATION from PYRUVATE via NEW STEPS in GLUCOSE FORMATION from PYRUVATE via GLUCONEOGENESISGLUCONEOGENESIS
PEP is formed from pyruvate by way of PEP is formed from pyruvate by way of oxaloacetateoxaloacetate
PyruvatePyruvate + CO + CO22 + ATP + HOH ------------ + ATP + HOH ------------ oxaloacetateoxaloacetate + ADP + Pi + 2H + ADP + Pi + 2H++
OxaloacetateOxaloacetate + GTP ------------- + GTP ------------- PEPPEP + GDP + CO + GDP + CO22
F-6-P is formed from F-1,6-BP by hydrolysis of F-6-P is formed from F-1,6-BP by hydrolysis of the phosphate ester at carbon 1, an the phosphate ester at carbon 1, an exergonic exergonic hydrolysishydrolysis
Fructose-1,6-bisphosphateFructose-1,6-bisphosphate + HOH -------------- + HOH -------------- fructose-6-phosphatefructose-6-phosphate + Pi + Pi
Glucose is formed by hydrolysis of G-6-PGlucose is formed by hydrolysis of G-6-P
Glucose-6-phosphate + HOH -------------Glucose-6-phosphate + HOH ------------- glucose + Pi glucose + Pi
Pyruvate carboxylase
PEP carboxykinase
Fructose-1,6-bisphosphatase
Glucose-6-phosphatase
RECIPROCAL REGULATION OF GLYCOLYSIS & RECIPROCAL REGULATION OF GLYCOLYSIS & GLUCONEOGENESISGLUCONEOGENESIS
Glucose
Fructose-6-phosphate
Fructose-1,6-bisphosphate
PEP
Pyruvate
Oxaloacetate
PFK F-1,6-BPase
Several steps
PK
PEP carboxykinase
Pyruvate carboxylase
GLUCONEOGENESIS
F-2,6-BP +
AMP +
ATP -
Citrate -
H+ -
F-2,6-BP -
AMP -
Citrate +
F-1,6-BP +
ATP -
Alanine -AcetylCoA +
ADP -
ADP -
GLYCOGEN GLYCOGEN Readily mobilized storage form of glucoseReadily mobilized storage form of glucose very large, branched polymer of glucose very large, branched polymer of glucose
residues linked via residues linked via αα-1,4 (straight) and -1,4 (straight) and αα--1,6 glycosidic bonds1,6 glycosidic bonds
branching occurs for every 10branching occurs for every 10thth glucose glucose residue of the open helical polymerresidue of the open helical polymer
not as reduced as fatty acids are and not as reduced as fatty acids are and consequently not as energy-richconsequently not as energy-rich
serves as buffer to maintain blood sugar serves as buffer to maintain blood sugar levelslevels
Released glucose from glycogen can provide Released glucose from glycogen can provide energy anaerobically unlike fatty acidsenergy anaerobically unlike fatty acids
Two major sites of glycogen storage are the Two major sites of glycogen storage are the liver (10% by weight) and skeletal muscles (2% liver (10% by weight) and skeletal muscles (2% by weight)by weight)
In the liver, its synthesis and degradation are In the liver, its synthesis and degradation are regulated to maintain normal blood glucoseregulated to maintain normal blood glucose
in the muscles, its synthesis and degradation is in the muscles, its synthesis and degradation is intended to meet the energy needs of the intended to meet the energy needs of the muscle itselfmuscle itself
present in the cytosol as granules (10-40nm)present in the cytosol as granules (10-40nm)
GLYCOGENOLYSISGLYCOGENOLYSIS Consists of three stepsConsists of three steps
1. 1. release of glucose-1-phosphate from release of glucose-1-phosphate from from the nonreducing ends of from the nonreducing ends of glycogen glycogen (phosphorolysis) (phosphorolysis)
2. 2. remodeling of glycogen substrate to remodeling of glycogen substrate to permit further degradation with a permit further degradation with a
transferase transferase and and αα-1,6 -1,6 glucosidaseglucosidase
3. 3. conversion of glucose-1-phosphate conversion of glucose-1-phosphate to glucose-6-phosphate for further to glucose-6-phosphate for further
metabolismmetabolism
Fates of Glucose-6-PhosphateFates of Glucose-6-Phosphate Initial substrate for Initial substrate for glycolysisglycolysis
Can be processed by the Can be processed by the pentose pentose phosphate pathwayphosphate pathway to NADPH and to NADPH and ribose derivativesribose derivatives
Can be Can be converted to free glucoseconverted to free glucose in the in the liver, intestine and kidneys for release into liver, intestine and kidneys for release into the blood streamthe blood stream
GlycogenGlycogen
Glycogen Glycogen n-1n-1
Glucose-1-phosphateGlucose-1-phosphate
Glucose-6-phosphateGlucose-6-phosphate
GlycolysisGlycolysis PPPPPP
PyruvatePyruvate GlucoseGlucose Ribose + Ribose + NADPHNADPH
Lactate Lactate COCO22 + HOH + HOH
Blood for use byBlood for use by other tissuesother tissues
Muscle,Brain
Liver
Glycogen phosphorylase
Glucose-6-phosphatase
Phosphoglucomutase
GLYCOGENESISGLYCOGENESIS Regulated by a complex system and requires a Regulated by a complex system and requires a
primer, primer, glycogeninglycogenin
Requires an Requires an activated form of glucoseactivated form of glucose, the, theUridine diphosphate glucose (UDP-Uridine diphosphate glucose (UDP-
glucose) formed from UTP and glucose) formed from UTP and glucose-1-glucose-1-phosphatephosphate
UDP-glucose is added to the nonreducing UDP-glucose is added to the nonreducing end of end of glycogen glycogen using using glycogen synthaseglycogen synthase, the key , the key
regulatory enzyme in glycogen synthesisregulatory enzyme in glycogen synthesis
Glycogen is then remodeledGlycogen is then remodeled for continued for continued synthesissynthesis
GLYCOGEN BREAKDOWN & SYNTHESIS ARE GLYCOGEN BREAKDOWN & SYNTHESIS ARE RECIPROCALLY REGULATEDRECIPROCALLY REGULATED
Glycogen breakdownGlycogen breakdown Glycogen synthesisGlycogen synthesis Epinephrine
Adenylate cyclase Adenylate cyclase
ATP cAMP
Protein kinase A Protein kinase A
Phosphorylase kinase Phosphorylase kinase
Phosphorylase b Phosphorylase a
Glycogen synthase a Glycogen synthase b
PINK – inactive GREEN - active
GLYCOGEN STORAGE DISEASEGLYCOGEN STORAGE DISEASETYPETYPE DEFECTIVE DEFECTIVE
ENZYMEENZYMEORGAN AFFECTEDORGAN AFFECTED GLYCOGEN IN GLYCOGEN IN
AFFECTED ORGANAFFECTED ORGANCLINICAL FEATURESCLINICAL FEATURES
I (Von Gierke)I (Von Gierke) Glucose-6-Glucose-6-phosphatasephosphatase
Liver & kidneyLiver & kidney Increased amount; Increased amount; normal structurenormal structure
Hepatomegaly, failure to thrive, Hepatomegaly, failure to thrive, hypoglycemia, ketosis, hypoglycemia, ketosis, hyperuricemia, hyperlipidemiahyperuricemia, hyperlipidemia
II (Pompe dse)II (Pompe dse) αα-1,4 glucosidase-1,4 glucosidase All organsAll organs Massive increase in Massive increase in amount; normal amount; normal structurestructure
Cardiorespiratory failure causes Cardiorespiratory failure causes death usually before age 2death usually before age 2
III (Cori dse)III (Cori dse) Amylo-1,6-Amylo-1,6-glucosidase glucosidase (debranching)(debranching)
Muscle & liverMuscle & liver Increased amount; Increased amount; short outer branchesshort outer branches
Like type 1 but milderLike type 1 but milder
IV (Andersen IV (Andersen dse)dse)
Branching enzyme Branching enzyme ((αα-1,4 & 1,6)-1,4 & 1,6)
Liver & spleenLiver & spleen Normal amount; very Normal amount; very long outer brancheslong outer branches
Progressive cirrhosis of the liver; Progressive cirrhosis of the liver; liver failure causes death before liver failure causes death before age 2age 2
V (McArdle dse)V (McArdle dse) PhosphorylasePhosphorylase musclemuscle Moderately Moderately increased amount; increased amount; normal structurenormal structure
Limited ability to perform Limited ability to perform strenuous exercise because of strenuous exercise because of painful muscle cramps. painful muscle cramps. Otherwise patient is normal or Otherwise patient is normal or well-developed.well-developed.
VI (Hers dse)VI (Hers dse) PhosphorylasePhosphorylase liverliver Increased amountIncreased amount Like type 1 but milderLike type 1 but milder
VIIVII PhosphofructokinPhosphofructokinasease
musclemuscle Increased amount; Increased amount; normal structurenormal structure
Like type VLike type V
VIIIVIII Phosphorylase Phosphorylase kinasekinase
liverliver Increased amount; Increased amount; normal structurenormal structure
Mild liver enlargement. Mild Mild liver enlargement. Mild hypoglycemiahypoglycemia
top related