Carbohydrate Metabolism II - Biochem - Final Exam

What is the order of preference fuel usage?

1. carbohydrate

2. fats

3. proteins

What are the characteristics of fats for fuel?

-stored in large amounts in small volume

-fatty acids

-cannot be metabolized anaerobically

What is the major storage form of carbohydrates?

glycogen

What are the amounts of liver glycogen in percentage of tissue weight and body content?

5-10% and 100-150 g

What are the amounts of muscle glycogen in percentage of tissue weight and body content?

1-2% and 250-400 g

What are the amounts of extracellular glucose in percentage of tissue weight and body content?

0.1% and 10 g

What is muscle glycogen for?

readily available source of glucose for glycolysis within the muscle (only useful for muscle)

When do liver glycogen stores increase?

fed state

What happens after 12-18 hours of fasting?

complete depletion of liver glycogen

What does the liver glycogen do?

release glucose in fasting state to maintain blood glucose levels to support basal function of tissues

What is the purpose of extensive branching?

-enhance solubility

-accelerate synthesis

-increase sites for degradation

What does branching do?

increases the number of non reducing sites meaning new glucose can be added or released rapidly by enzymes

Where does glycogen synthesis occur?

cytosol

Glycogenesis

synthesis of glycogen

What is needed for the initation of glycogen synthesis?

preexisting piece of glycogen or primer called glycogenin

What is glycogenin?

protein with autocatalytic activity capable of synthesizing glycogen

How many steps are in glycogenesis?

4

What is the first step of glycogenesis?

glucose to glucose 6-PO4 to glucose 1-PO4

What are the additional compounds needed for step one of glycogenesis?

ATP, glucokinase in the liver, hexokinase in the muscle for conversion to glucose 6-P and phosphoglucomutase for conversion to glucose 1-P

What is the second step of glycogenesis?

formation of UDP-glucose

What are the additional compounds needed for step 2 of glycogenesis?

UDP-glucose pyrophosphorylase and UTP to PPi

What is the third step of glycogenesis?

addition of glucoses for glycogen chain elongation to make alpha 1 - 4 linkages

What additional compounds are needed for step 3 of glycogenesis?

glycogen synthase

What is the fourth step of glycogenesis?

formation of branches to extend glycogen structure by branching enzyme to make alpha 1 - 6 linkages

What additional compound is needed for step 4 of glycogenesis?

4 - 6 transferase

What kind of bond is created in step 3 of glycogenesis?

alpha 1 - 4 glycosidic bond between UDP-glucose and another glucose residue

How is glycogen elongated?

addition of 8-10 glucoses on non-reducing end

What is the branching step in step 4 of glycogenesis?

detachment of fragment (5-6 glucose) by branching enzyme from non reducing end of alpha 1 - 4 and linking it to another glucose in the chain or neighboring chain by alpha 1 - 6

Where does glycogen degradation occur?

cytosol

What is the primary end product of glycogen degradation?

glucose 1-P and free glucose from each alpha 1-6 linkage

How many steps are in glycogen degradation?

3

What is step one of glycogen degradation?

shortening of glycogen chains and release of glucose 1-P by glycogen phosphorylase

What is step two of glycogen degradation?

-removal and transfer of branches by debranching enzyme 4:4 transferase from limit dextrin

-hydrolysis of alpha 1 -6 linkages by debranching enzyme alpha 1 - 6 glucosidase

What is step three of glycogen degradation?

conversion of glucose 1-P to glucose 6-P by phosphoglucomutase

What is the purpose of glycogen breakdown in liver?

to use during fasting to increase glucose levels

What is the purpose of glycogen breakdown in muscle?

meet the energy needs of the muscle but does not contribute to blood glucose levels because it lacks the enzyme glucose 6-P necessary for the conversion

How is glycogen synthesis and breakdown regulated?

by allosteric regulation of glycogen synthase and glycogen phosphorylase

How do the regulator molecules change in fasting in the liver?

glucagon increases and insulin decreases

What is the tissue response of the fasting state?

glycogen degradation increases and glycogen synthesis decreases

How do the regulator molecules change after a carbohydrate meal in the liver?

glucagon decreases and glucose and insulin increase

What is the tissue response after a carbohydrate meal in the liver?

glycogen degradation decreases and glycogen synthesis increases

How do the regulator molecules change during exercise and stress in the liver?

epinephrine increases

What is the tissue response to exercise and stress in the liver?

glycogen degradation increases and glycogen synthesis decreases

How do the regulator molecules change in fasting in the muscle?

insulin decreases

What is the tissue response to fasting in the muscle?

glycogen synthesis and glucose transport decreases

How do the regulator molecules change after a carbohydrate meal?

insulin increases

What is the tissue response after a carbohydrate meal in the muscle?

glycogen synthesis and glucose transport increases

How do the regulator molecules change during exercise and stress in the muscle?

epinephrine rises

What is the tissue response during exercise and stress in the muscle?

glycogen degradation and glycolysis increase and glycogen synthesis decreases

What does insulin activate?

protein phosphatase, then glycogen synthase (takes off the phosphate to make it active) to increase glycogenesis

What does glucagon activate?

protein kinase to activate glycogen phosphorylase by adding a phosphate to activate glycogenolysis

How are glycogen storage disorders characterized?

deposition of an abnormal type of glycogen due to imparied synthesis or abnormal quantity of glycogen due to impaired degradation due to defective enzymes

Glycogen synthase deficiency is type...

type 0

What happens in glycogen synthase deficiency?

elongation of glycogen does not occur and a hypoglycemic state occurs which leads to hyperketonemia and early death

What are the other names for glucose 6-P deficiency?

Von Gierke's disease or type I

What happens in glucose 6-Posphatase deficiency?

glycogen accumulates as it cannot degrade which leads to severe fasting hypoglycemia as it cannot be released into the blood

What does glucose 6-Posphatase deficiency effect?

liver and kidney (megaly), progessive renal disease and fatty liver, hyperlipidemia, hyperlacticacidemia, growth retardation and delayed puberty

What is not effected by glucose 6-phosphatase defiency?

muscle tissue

How do you treat glucose 6-phosphotase deficency?

administration of uncooked starch

What are other names of lysosomal alpha 1 -4 and alpha 1 -6 glucosidase deficiency?

Pompe's Disease and type II

Why does Pompe's disease occur?

inborn lysosomal enzyme defect in liver, heart and muscle which accumulate glycogen in lysosomes

What is the result of Pompe's disease?

massive cardiomegaly due to heart muscle thickening and death from heart failure by age 2

What is the treatment of Pompe's disease?

enzyme replacement therapy

What are other names of limit dextrinosis, debranching enzyme deficiency?

Forbe's or Cori's disease, type III

What happens in debranching enzyme deficiency?

accumulation of characteristic branched glycogen limit dextrin, fasting hypoglycemia and hepatomegaly in infancy

What are the other names of branching enzyme 4 - 6 transferase deficiency?

Amylopectinosis - Andersen's disease, type IV

What happens in branching enzyme 4 - 6 transferase deficiency?

accumulation of glycogen with limited branches, hepatosplenomegaly and death from heart/liver failure in first year of life

What are the other names of skeletal muscle glycogen phosphorylase deficiency?

McArdle's syndrome or type V

What happens in McArdle's syndrome?

muscle glycogen is abnormally high and there is a poor exercise tolerance leading to weakness and cramping. there is no rise in blood lactate during exercise and it can cause myoglobinemia and myoglobinuria

What is not effected by McArdle's syndrome?

liver

Gluconeogenesis

process of synthesizing glucose using compounds other than carbohydrates

What is gluconeogenesis a reversal of?

glycolysis

When does the body turn to gluconeogenesis for energy?

-prolonged fasting

-starvation

-diet with insufficient carbohydrates

What can happen from failure of gluconeogensis?

it can be fatal as brain and RBC need glucose and without it can lead to coma and death

What are the major tissues involved in gluconeogenesis?

liver and kidney

What are the main non-carbohydrate compounds used for conversion to glucose?

1. lactate

2. glycerol

3. propionate

4. glucogenic amino acids

What produces lactate?

exercising skeletal muscle and RBC by anaerobic glycolysis

What is the fate of lactate in the liver?

reconverted to pyruvate with lactate dehydrogenase and NAD+ to be utilized for glucose

What produces glycerol?

fat hydrolysis

What is the fate of glycerol in the liver?

converted to dihydroxy acetone phosphate with NAD+ and glycerol PO4 dehydrogenase

What produces glucogenic amino acids?

tissue breakdown during fasting

What do glucogenic amino acids provide?

carbon skeleton gives pyruvate or one of the intermediates of TCA

What is the fate of odd chain fatty acids?

create propionate from beta oxidation

What is the exception to the steps of the gluconeogenic pathway?

same as glycolysis besides 3 steps

What are the three steps that are different in gluconeogenic pathway?

glucose to glu 6-P with hexokinase

fructose 6-P to fructose 1,6 di-P with PFK-1

phosphoenol pyruvate to pyruvate with pyruvate kinase

What is bypass step 1?

two stages

-conversion of pyruvate to oxaloacetate in mitochondria with CO2, biotin, ATP and pyruvate carboxylase

-conversion of oxaloacetate to phosphoenolpyruvate in cytosol via malate-aspartate shuttle with GTP and phosphoenolpyruvate carboxy-kinase excreting CO2 and GDP

What is bypass step 2?

fructose-1,6 bis PO4 to fructose-6 PO4 with fructose bis-phosphatase and a release of Pi

What is bypass step 3?

glucose 6-P to glucose with glucose 6-phosphatase and a release of Pi

What are the regulatory enzymes of gluconeogenesis?

-glucose 6 phosphatase

-fructose 1,6 bisphosphatase

-pyruvate carboxylase

When is fructose 1,6 bisphosphatase active?

only during fasting/starvation to promote gluconeogenesis and kept inhibited in fed state

When is glucose 6-phosphatase active?

during fasting by glucagon and repressed by insulin

When is pyruvate carboxylase active?

by acetyl coA which is available from fat breakdown during prolonged fasting/starvation

What is the process of prologed fasting?

increase release of fatty acids from adipose, increase fatty acid oxidation, increase of Acetyl CoA to activate pyruvate carboxylase and deactivate pyruvate dehydrogenase so pyruvate will form oxaloacetate

What form are the gluconeogenesis glycolysis regulatory enzymes in?

inactive state so that the pyruvate is mostly used to convert to glucose

What are other names for the hexose monophosphate shunt?

-HMP shunt

-Pentose Phosphate pathway

-6-phosphogluconate pathway

What is the hexose monophosphate shunt?

alternative route for the oxidative metabolizm of glucose that is oxidized to CO2 but does not generate ATP

What does the HMP shunt produce?

6 co2, 12 NADPH, 5 glucose 6-P

What do you need for complete oxidation of glucose?

6 glucoses

What are the major functions of HMP shunt?

1. generate NADPH

2. pentose sugar formation for DNA and RNA synthesis

3. mechanism for metabolic use of 5 carbon sugars obtained from diet and degradation of body structural carbs

Where is the HMP shunt active in?

-liver

-adipose

-adrenal cortex

-gonads