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39 Cards in this Set

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The requirement for glucose is continuous...

1) glucose is the preferred fuel source for all tissues




2)the brain and red blood cells have a continuous dependence on glucose

Glucokinase only works when...

glucose concentration is high---> glucokinase has a high Km.

what is the physiological circulating blood glucose concentration?




what is the fasting glucose concentration?

- physiological circulating glucose concentration = 3.9-6.2mM






- average fasting glucose concentration is = 4.4 - 5 mM

what glucose concentration level is fatal?

if it drops to 2.5 or less coma and death can result

if glucose concentration rises for an extended time...

dehydration, wasting of body tissue and eventually death will result.




(dehydration can be explained as if blood glucose concentration is very high, glucose cannot be selectively reabsorbed by the kidney so it is lost in urine, waste muscle is because if you can't control blood glucose you keep going gluconeogenesis)

The roles of glucose...

1) it is a source of energy




2) it is a source of NADPH (needed for fatty acid synthesis)




3) it is a source of pentose sugars for synthetic reactions (nucleotides, DNA)




4) it is a source of carbon for other sugars

what are the advantages of using glucose as a metabolic fuel...

- glucose is water soluble so it does not require a carrier in the circulation




- glucose can cross the blood brain barrier




- glucose can be oxidised anaerobically---> allows glycolysis to continue

what are the disadvantages of using glucose as a fuel...

-relatively low yield of ATP/mole compared to fatty acids




-osmotically active so you can't store a lot of it




-in high concentrations can directly damage cells or lead to accumulation of toxic by-products (fructose, sorbitol)

explain the role of glucose in skeletal muscle...

1) glycolysis---> anaerobic muscle contraction




2) glycolysis/TCA cycle---> energy




3) glycogen synthesis and degradation---> energy store for muscle contraction.

explain the role of glucose in the brain...

1) the brain has a high oxidative metabolism---> glycolysis/TCA cycle---> energy

explain the role of glucose in adipose tissue...

1) glycerol---> glycolysis---> production of gycerol for TAGs

explain the role of glucose in the liver...

1) glycolysis/TCA cycle---> production of acetyl CoA (the liver doesn't do glycolysis for energy, it does glycolysis to make fatty acids via acetylCoA)




2) pentose phosphate---> NADPH, pentoses




3) glycogen synthesis/ glycogenolysis---> glucose storage for other tissues




4) gluconeogenesis---> glucose for other tissues

can you convert fatty acids to glucose?

no because pyruvate to acetyl CoA is irreversible

list the sources of blood glucose...

1) diet




2) liver glycogen




3) liver gluconeogenesis (starvation)

define gluconeogenesis...

-making glucose from non-carbohydrate sources e.g lactate, glycerol, other monosaccharides and glucogenic amino acids (except leucine and lysine)




occurs in conditions of carbohydrate deprivation

gluconeogenesis is not simply the reversal of glycolysis...

there are 3 irreversible reactions in glycolysis that must be bypassed:


1) glucose ----> glucose-6-phosphate (hexokinase/glucokinase)




2) fructose-6-phosphate----> fructose-1,6-bisphosphate (phosphofructokinase)




3) phosphoenolpyruvate ---> pyruvate (pyruvate kinase)




all in the cytosol

How are the 3 irreversible reactions of glycolysis bypassed in gluconeogenesis?

1) pyruvate<----> oxaloacetate <---> phosphoenol pyruvate




catalysed by pyruvate carboxylase and phosphoenol carboxy kinase.




first reaction is an addition of CO2 and the second is a removal of CO2.




first uses ATP (makes ADP), second uses GTP (GDP is made)



the second bypass is...

fructose-1,6-bisphosphate ----> fructose-6-phosphate + Pi




addition of water/hydration reaction




catalysed by fructose-1,6-bisphophatase

the third bypass is...

glucose-6-phosphate ------> glucose + Pi




addition of water/hydration reaction




catalysed by glucose-6-phosphatase

how is gluconeogenesis regulated?

1) mobilisation of substrate (glycerol from fat breakdown, amino acids from muscle protein breakdown)




2) activation of enzymes (glucagon activates gluconeogenesis enzymes, activation of pyruvate carboxylase by acetyl CoA*)




*breaking down fat produces acetyl CoA which activates gluconeogensis enzymes

is the conversion of lactate to pyruvate reversible in all tissues?

no- only in the liver.




anaerobic respiration is only reversible in the liver.

how is blood glucose maintained...

1) Insulin, glucagon and adrenaline (and to a lesser extent cortisol) and glucose itself, signal and coordinate the activities of:


-liver


-adipose tissue


-muscle tissue

why is gluconeogenesis so important?

vital to preserve brain function

insulin is an...

anabolic hormone secreted from the beta cells in the islets of langerhans.




it promotes synthesis and storage and inhibits degradation of stored fuel




lowers blood glucose levels

glucagon is a...

catabolic hormone secreted from the alpha cells in the iselts of langerhans




it promotes degradation of stored fuel and inhibits synthesis and storage




raises blood glucose

list the metabolic effects of insulin in the liver...

- inhibition of gluconeogenesis


- activation of glycogen synthesis (glycogen synthase is activated)


- increased fatty acid synthesis and lipid assembly


-increased amino acid uptake and protein synthesis

list the metabolic effects of insulin in the muscle...

-increased glucose uptake by increasing glucose transporters (GLUT4)


-increased amino acid uptake and protein synthesis


-activation of glycogen synthesis (glycogen synthase activated)- muscle in the fed state will make glycogen.




(No effect on gluconeogenesis)

list the metabolic effects of glucagon...

- increase in blood glucose (glycogenolysis and gluconeogenesis in the liver)


-increase in circulating fatty acids and ketone bodies (increase in adipose tissue lipolysis, increase in fatty acid oxidaton in the liver and ketone body formation)


-decrease in plasma amino acids (increase in uptake by the liver for gluconeogenesis)

in the liver in the fasting state, pyruvate is not converted into acetylCoA...

so pyruvate is converted to glucose instead of acetylCoA (gluceneogensis)




insulin inhibits pyruvate---> acetylCoA (pyruvate dehydogenase is inhibited)

discuss the differences between hexokinase (muscle) and glucokinase (liver)...

Hexokinase- remains active even at low glucose levels (high affinity for glucose, low km), lower Vmax; saturated at relatively low glucose concentration, allosteric, induced by insulin, is inhibited by product (feedback inhibition)




Glucokinase- only works at high glucose concentration, low affinity for glucose; higher Km and higher Vmax, has to rapidly breakdown glucose to bring down levels to what they should be, not inhibited by product.

liver glycogen is used for maintaining blood glucose levels while muscle glycogen is used for...

an energy store for muscle contraction.

the liver synthesises glucose at all times except in the...

fed state

The first bypass (pyruvate--->oxaloacetate) which is catalysed by pyruvate carboxylase...

also has an important role in topping up the TCA cycle.




Then oxaloacetate + GTP ---> PEP + GDP + CO2



To summarise, once phosphoenol pyruvate is formed, the reactions of glycolysis are reversible until fructose-1,6-bisphosphate is reached. This is bypassed by removing/hydrolysing the phosphoryl group from the 1,6 compound...

fructose-1,6-bisphosphate + H20----> fructose-6-phosphate + Pi




catalysed by fructose-1,6-bisphosphatase

the third bypass reaction is...

glucose-6-phosphate + H20 ----> glucose




catalysed by glucose-6-phosphatase

Therefore there are 4 enzymes involved in gluconeogenesis that do not participate in glycolysis which are...

pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase and glucose-6-phosphatase.

In fasting and starvation, when the glycogen reserves have been exhausted, the main source of pyruvate is...

the breakdown of muscle proteins.



insulin concentration is low/glucagon conc is high which stimulates uptake of amino acids by the liver for gluconeogenesis.

About 50% if the amino acids leaving the muscle to be transported to the liver and in the form of alanine and glutamine.

what is meant by glucogenic amino acids?

it means their carbon skeleton is capable of being converted into glucose by the liver




alanine and glutamine are both glucogenic amino acids.