Welcome to Scribd, the world's digital library. Read, publish, and share books and documents. See more
Download
Standard view
Full view
of .
Save to My Library
Look up keyword
Like this
5Activity
0 of .
Results for:
No results containing your search query
P. 1
Integration of Metabolism

Integration of Metabolism

Ratings: (0)|Views: 2,965|Likes:
Published by Dr. KaushaL PateL
Summary of allosteric effectors and hormonal control of key regulatory
enzymes in primary metabolic pathways
Factors that influence release of insulin, glucagon, and epinephrine
Metabolic adaptations and tissue interactions in well-fed, fasting, and
starvation states
Comparison of type 1 and type 2 diabetes mellitus
Comparison of metabolic changes in untreated type 1 diabetes and
starvation
Hepatic metabolism of alcohol and its metabolic consequences; fetal
alcohol syndrome
Summary of allosteric effectors and hormonal control of key regulatory
enzymes in primary metabolic pathways
Factors that influence release of insulin, glucagon, and epinephrine
Metabolic adaptations and tissue interactions in well-fed, fasting, and
starvation states
Comparison of type 1 and type 2 diabetes mellitus
Comparison of metabolic changes in untreated type 1 diabetes and
starvation
Hepatic metabolism of alcohol and its metabolic consequences; fetal
alcohol syndrome

More info:

Categories:Topics, Art & Design
Published by: Dr. KaushaL PateL on Jul 25, 2010
Copyright:Attribution Non-commercial

Availability:

Read on Scribd mobile: iPhone, iPad and Android.
download as PDF, TXT or read online from Scribd
See more
See less

11/16/2012

pdf

text

original

 
9
 Integrationof Metabolism
Target Topics
Summary of allosteric effectors and hormonal control of key regulatoryenzymes in primary metabolic pathwaysFactors that influence release of insulin, glucagon, and epinephrineMetabolic adaptations and tissue interactions in well-fed, fasting, andstarvation statesComparison of type 1 and type 2 diabetes mellitusComparison of metabolic changes in untreated type 1 diabetes andstarvationHepatic metabolism of alcohol and its metabolic consequences; fetalalcohol syndrome
I. Hormonal Regulation of Metabolism
A.
Introduction
1.
Hormones
act by triggering
intracellular signaling path-ways
leading to coordinated
activation and/or deacti-vation of key enzymes
(usually by phosphorylation or de-phosphorylation),
induction and/or repression of enzymesynthesis,
or both.
2.
Three hormones—
insulin, glucagon,
and
epinephrine
play a critical role in
integrating metabolism,
especially en-ergy metabolism, in different tissues (Table 9-1).
Allosteric effectors,
molecules that bind at a site otherthan the active site and activate or inhibit particularenzymes, are also important in
regulation of metabolicpathways
(see Table 9-1).
3.
Insulin
and
glucagon
are the key hormones in the
short-term regulation of blood glucose concentration
undernormal physiologic conditions.
164
 
TABLE 9-1 Allosteric and Hormonal Regulation of Metabolic Pathways
MetabolicPathwayMajor RegulatoryEnzyme(s) Allosteric Effectors*HormonalEffects†
Glycolysis andpyruvateoxidationHexokinaseGlucokinase (liver)Phosphofructoki-nase 1Pyruvate kinasePyruvatedehydrogenaseGlucose 6-P (–)Fructose 2,6-BP, AMP(+); citrate (–)Fructose 1,6-BP (+);ATP, alanine (–)ADP (+); acetyl CoA,NADH, ATP (–)Induced byinsulinGlucagon (
) viadecrease infructose 2,6-BPGlucagon (
)Insulin (
)Citric acid cycle IsocitratedehydrogenaseADP (+); ATP, NADH (–) Glycogenesis GlycogensynthaseGlucose 6-P (+) Insulin (
);glucagon inliver, epi-nephrine inmuscle (
)Induced byinsulinGlycogenolysis GlycogenphosphorylaseCa
2+
(+) in muscle Glucagon in liver,epinephrine inmuscle (
)Gluconeogenesis Fructose-1,6-bisphosphatasePEP carboxykinasePyruvatecarboxylaseCitrate (+); fructose2,6-BP, AMP (–)Acetyl CoA (+)Glucagon (
) viadecrease infructose 2,6-BPAll three enzymesinduced byglucagon andcortisol;repressed byinsulinPentose phos-phate pathwayGlucose-6-phosphatedehydrogenase(G6PD)NADPH () Fatty acidsynthesisAcetyl-CoAcarboxylaseCitrate (+); palmitate (–) Insulin (
);glucagon (
)Induced byinsulinLipolysis Hormone-sensitivelipaseEpinephrine (
);insulin (
)
β
-Oxidation offatty acidsCarnitineacyltransferaseMalonyl CoA () CholesterolsynthesisHMG-CoAreductaseCholesterol () Insulin (
);glucagon (
)Urea cycle Carbamoyl phos-phate synthe-tase I (CPS I)
-Acetylglutamate (+) PyrimidinesynthesisCarbamoyl phos-phate synthe-tase II (CPS II)PRPP, ATP (+); UTP (–) Purine synthesis PRPPamidotransferasePRPP (+); IMP, AMP,GMP (–)Heme synthesis ALA synthase Enzyme synthesisrepressed by heme
*Stimulates (+) or inhibits (
) enzyme activity.
Promotes formation of active form (
) or inactive form (
) of enzyme via phosphorylation/ dephosphorylation.
165
Chapter 9 Integration of Metabolism
 
a.
Insulin
acts to
reduce blood glucose
(hypoglycemiceffect).
b.
Glucagon
acts to
increase blood glucose
(hyperglycemiceffect).
B.
Insulin
is synthesized by pancreatic
cells
as an inactive pre-cursor,
proinsulin.
1.
Proteolytic cleavage
of proinsulin yields
C-peptide
and
active insulin,
consisting of disulfide-linked
A and Bchains.
2.
Secretion of insulin
is regulated by circulating substratesand hormones.
a.
Stimulated
by
increased blood glucose
(most impor-tant)
, increased individual amino acids
(e.g., arginine,leucine), and
gastrointestinal hormones
(e.g.,
secre-tin
), which are released after ingestion of food
b.
Inhibited
by
somatostatin
and
low glucose
3.
Metabolic actions of insulin
are most pronounced in
liver,muscle,
and
adipose tissue.
Overall effect is to
promote storage of excess glucose
asglycogen in liver and muscle and as triacylglycerols inadipose tissue.
4.
Insulin receptor 
is a tetramer whose cytosolic domain has
tyrosine kinase activity
for generating second messen-gers (see Chapter 3).
a.
Insulin binding triggers signaling pathways
thatproduce several cellular responses (post-receptorfunctions).
b.
Increased adipose tissue down-regulates
insulin recep-tor synthesis, while
weight loss up-regulates
receptorsynthesis.
c.
Increased glucose uptake
by muscle and adipose tissueis due to
translocation of GLUT4
receptors to cellsurface.
d.
Activation of energy-storage enzymes
(e.g., glycogensynthase) and
inactivation of energy-mobilizing enzymes
(e.g., glycogen phosphorylase) is due to
dephos-phorylation
of these enzymes.
e.
Increased enzyme synthesis
(e.g., glucokinase,phosphofructokinase) is due to activation of genetranscription.
C.
Glucagon
and
epinephrine
function to
prevent fasting hypoglycemia.
1.
Secretion of glucagon
from pancreatic
cells
is regulatedby circulating substrates and hormones.
a.
Stimulated
by
decreased blood glucose, increasedamino acids,
and
increased epinephrine
b.
Inhibited
by
insulin
2.
Secretion of epinephrine
from the
adrenal medulla
is trig-gered by release of acetylcholine from
preganglionic sym-pathetic nerves
in response to
stress,
prolonged
exercise,
or
trauma.
Insulin causesenzyme dephos-phorylation; gluca-gon causes enzymephosphorylation.
166
Biochemistry

Activity (5)

You've already reviewed this. Edit your review.
1 hundred reads
1 thousand reads
Wesam A. Nasif liked this
klavdaki3823 liked this
ramadan liked this

You're Reading a Free Preview

Download
/*********** DO NOT ALTER ANYTHING BELOW THIS LINE ! ************/ var s_code=s.t();if(s_code)document.write(s_code)//-->