biochem glycogen

glycogenesis

glucose converted in liver into glycogen

glycogenolysis

hepatic glycogen used to maintain blood glucose

gluconeogenesis

shift from glycogenolysis to de novo synthesis of glucose from non carbohydrate compounds

during physical activity, what provides energy

glycogen derived glucose

what is also stored in muscle but isnt available for blood glucose maintenance

glycogen

what is essential during fasting or starvation (where glycogen stores depleted)*

gluconeogenesis*

what is the primary precursor of glucose

amino acids from muscle protein

gluconeogenesis is use of

lactate from glycolysis and glycerol from fat catabolism

what provides energy for gluconeogenesis

mobilization of fatty acids from adipose tissue

what is glycogen

a complex carbohydrate

muscle contains high amount of glycogen, but is it shared amongst other parts of the body or soley used for itself

mainly used for itself, a self reserve of glycogen for the muscle only

glycogen has a ________ linkage at a-1,4 and ________ linkage at a-1,6

linear, branch

glycogen structure look similar to

cauliflower head

in cauliflower head of glycogen whats in the middle

enzymes that are needed for its metabolism surround membrane

synthesize glycogen when we have excesssive glucose levels in the

blood

step 1 of glycogenesis

UDP Glucose is FLAG that tells next enzyme to use itself to build glycogen, this enzyme is glucokinase (same as hexokinase but liver specific)

step 2 of glycogenesis

build linear chain from UDP glucose, using glycogen synthase which is main regulatory enzyme of glycogenesis

step 3 of glycogenesis

create branches from linear chain using branching enzyme, without branching enzyme you would get long straight chain not real glycogen

UDP glucose

activated/flagged form of glucose needed for synthesis

glycogen synthase

main regulatory enzyme in glycogenesis

branching enzyme

essential for cauliflower shape of glycogen

when glycogen synthase is phosphorylated it becomes

inactive and stops glycogen synthesis

andersens disease

when branching enzyme not working properly causing long unbranched chain

glycogenolysis occur when

low blood glucose thus body needs to release glucose from glycogen storage

step 1 of glycogenolysis

break linear chain using glycogen phosphorylase (main regulatory enzyme)

step 2 of glycogenolysis

debranching enzyme (bi functional), once done glycogen phosphorylase break down chain again

role 1 of debranching enzyme

transfer about 4 residues to another chain

role 2 of debranching enzyme

remove single leftover residue at a-1,6 branch

step 3 of glycogenolysis

converting to free glucose (liver specific) using glucose 6 phosphatase, release free glucose into bloodstream

muscle does not have glucose 6 phosphatase enzyme because

it keeps glucose for itself

what happens in glycogenolysis if glucose 6 phosphatase isnt working

glucose cant be released into blood, and glycogen accumulate in liver

mechanism of action for glucagon

cell surface receptors

mechanism of action for cortisol

gene expression

hormonal regulators for glycogenolysis

glucagon, epinephrine, cortisol, insulin

glucagon initiator

hypoglycemia and stress

epinephrine initiator

stress and hypoglycemia

cortisol initiator

chronic stress

insulin initiator

hyperglycemia

what 3 hormones activate glycogenolysis

glucagon, epinephrine, insulin

glucagon step 1 for hormonal control of glucogenolysis

glucagon bind to GPCR receptor on liver cell

glucagon step 2 for hormonal control of glucogenolysis

G protein alpha subunit activate adenylyl cyclase

glucagon step 3 for hormonal control of glucogenolysis

adenylyl cyclase convert ATP to cAMP

glucagon step 4 for hormonal control of glucogenolysis

cAMP activate protein kinase A

glucagon step 5 for hormonal control of glucogenolysis

PKA activate phosphorylase kinase

glucagon step 6 for hormonal control of glucogenolysis

phosphorylase kinase activate glycogen phosphorylase

glucagon step 7 for hormonal control of glucogenolysis

glycogen phosphorylase break down glycogen to glucose 1,P

glucagon step 8 for hormonal control of glucogenolysis

glucose released into blood

PKA does what 2 things at the same time that makes sure glucose goes towards breakdown and not back into glycogen

actvivate glycogen phosphorylase, and phosphorylate & inactivate glycogen synthase (breakdown ON, synthesis OFF)

epinephrine goes through same cascade to glucagon BUT

-uses additional second messengers (IP3 +DAG→ PKC)

-related to stress/fight or flight response

-activate stress related metabolic pathways

insulin has opposite effect in glucogenolysis

-low blood sugar increases breakdown by glucagon/epinephrine

-high blood sugar increases synthesis by insulin

epinephrine in muscle

-muscle rich in glycogen

-muscle lack glucagon R and Glc-6-P

-glycogen muscle → no blood glucose

what is glycogenolysis in muscle activated by

epinephrine

insulin stimulates

glycogenesis, uptake in glucose, synthesis of enzymes

insulin inhibits

glycogenolysis

where does insulin stimulate uptake of glucose

in muscle and adipose tissue

what does insulin stimulate synthesis of enzymes for?

carbohydrate metabolism, storage and conversion of glucose to triglycerides

insulin activates

glycogen synthase

if glycogen synthase is activated what takes place

glycogenesis

what are sources for the carbon skeleton of hepatic gluconeogenesis

alanine, lactate, glycerol, fatty acids

gluconeogenesis is complete reverse of glycolysis (T/F)

F

in gluconeogenesis most steps are reversible (T/F)

T

what does glyconeogenesis need to bypass the 3 irreversible steps of glycolysis

4 unique enzymes

what are the 4 unique enzymes needed to bypass 3 glycolysis steps for gluconeogenesis

pyruvate carboxylase, PEPCK, fructose 1,6 bisphosphatase, glucose 6 phosphataase

what does pyruvate carboxylase and PEPCK bypass in glycolysis for gluconeogenesis

pyruvate kianse

what does fructose 1,6 bisphosphatase bypass in glycolysis for gluconeogenesis

phosphofructokinase-1 (PFK-1)

what does glucose 6 phosphatase bypass in glycolysis for gluconeogenesis

hexokinase/glucokinase

what is the regulatory point of gluconeogenesis

fructose 1,6 bisphosphatase

high fructose 1,6 bisphosphatase in gluconeogenesis causes

activate PFK-1 → glycolysis ON → gluconeogenesis OFF

low fructose 1,6 bisphosphatase in gluconeogenesis causes

activate F1,6 bisphosphatase → gluconeogenesis ON → glycolysis OFF

glucagon in response to low blood sugar

activates gluconeogenesis

insulin in response to high blood sugar

inhibits gluconeogenesis

gluconeogenesis and glycolysis are

reciprocally regulated, one inactive when other is active (vice versa)

hypoglycemia

glucagon present, glycogen depleted

-favors gluconeogenesis

-regulating molecule: fru2,6-bisphosphate

type 1 diabetes (10%)

unable to produce insulin

type 2 diabetes (90%)

secrete insulin but resistant

gestational diabetes

glucose intolerance diagnosed in pregnancy

obesity in type 1

uncommon

obesity in type 2

common

ketoacidosis in type 1

yes

ketoacidosis in type 2

possible (major stress)

onset of type 1

under 20 years age

onset of type 2

over 40 years age

insulin synthesis type 1

absent (destruction of B cells)

insulin synthesis type 2

preserved

Von Gierke’s

defect in Glucose-6-phosphatase

defect in Glucose-6-phosphatase

Liver can’t release free glucose, so you get severe fasting hypoglycemia and an enlarged liver full of glycogen leading to Von Gierke’s disease

Cori’s

defect in Debranching enzyme

defect in Debranching enzyme

Glycogenolysis stops at branch points, so abnormal, short-branched glycogen accumulates leading to Cori’s disease

Andersen’s

defect in branching enzyme

defect in branching enzyme

Glycogen is built with too few branches, so it’s abnormal and poorly soluble, damaging liver and other tissues leading to Andersen’s disease