Biochem Glycolysis and Gluconeogenesis

What is and who founded the vitalistic dogma

Fermentation of sugars to alcohol inextricably tied to living cells founded by Louis Pasteur in 1860

How did metabolism become chemistry?

Serendipitous finding by Hans and Eduard Buchner in 1897 with cell-free yeast extracts that fermentation could take place outside the cell.

What is the underlying unity in biochemistry

Studies of muscle extracts showed that many of the reactions of lactic acid fermentation were shared with alcoholic fermentation

Fermentation of produces what?

Ethanol and lactate

True or false: Glycolysis is an anaerobic process

True, oxygen is not required to complete glycolysis

What are the net products of the glycolysis of one glucose molecule?

2 pyruvate, 2 ATP, and 2 NADH+

In the lecture, glycolysis is broken into 3 stages. What happens in the 1st stage?

In the lecture, glycolysis is broken into 3 stages. What happens in the 2nd stage?

In the lecture, glycolysis is broken into 3 stages. What happens in the 3rd stage?

In glycolysis, glucose is phosphorylated to glucose 6-phosphate by________ and ATP

hexokinase

True or false: Glucose-6-phosphate is negatively charged and can pass back out through the plasma membrane

False: glucose-6-phosphate cannot pass through the plasma membrane; this is why glucose is quickly phosphorylated

Glucose-6-phosphate is converted to Fructose-6-phosphate by what enzyme?

Phosphoglucose isomerase

fructose 6-phosphate is phosphorylated to fructose 1,6-bisphosphate by ___________ and ATP

phosphofructokinase

True or false: phosphofructokinase contains additional binding sites for allosteric effectors

True. phosphofructokinase has several activators and inhibitors

The splitting of fructose 1,6-bisphosphate to DHAP and GAP is carried out by which enzyme?

Aldolase

How many glyceraldehyde-3-phosphates are produce per glucose?

Two of these 3 carbon units are produced for every six carbon glucose

What is the function of NAD+ in glycolysis?

Oxidizing agent and cofactor allowing inorganic phosphate to be added to GAP

3 stages of glycolysis are essentially irreversible. What are the enzymes at these 3 stages?

Hexokinase, phosphofructokinase, pyruvate kinase. Note: all are kinases

True or false: ATP acts as an allosteric activator for phosphofructokinase

False: ATP act as an allosteric inhibitor of phosphofructokinase

Name 3 activators of phosphofructokinase

AMP, insulin, fructose 2,6-bisphosphate

Which product (other than ATP) of the TCA cycle inhibits phosphofructokinase?

Citrate

What are the allosteric effectors of pyruvate kinase? specify activator or inhibitor

Alanine (inhibitor), Fructose 1,6-bisphosphate (activator)

True or false: The phosphorylation of pyruvate kinase inhibits the enzyme

True

Which hormone stimulates the expression of pyruvate kinase by effecting transcription?

Insulin

Where does galactose enter the glycolytic pathway?

Where does fructose from adipose tissue enter the glycolytic pathway?

Where does fructose from the liver enter the glycolytic pathway?

Why is there less regulation on fructose metabolism?

Fructose from the liver bypasses regulation of phosphofructokinase, does not lead to F-2,6-BP, hence less regulation on fructose metabolism

How is fructose modified for entry into the glycolytic pathway as GAP and DHAP?

Why does much fructose go to adipose tissue and converted to fat instead of being metabolized like glucose?

Hexokinase preferentially utilizes glucose rather than fructose

What is a common cause of galactosemia?

deficiency of galactose 1-phosphate uridyl transferase activity, which catalyzes conversion of galactose to glucose 6-phosphate

What are some symptoms of galactosemia?

vomiting and diarrhea after consumption of milk by infants; can eventually lead to mental retardation

Lactose intolerance is commonly caused by a deficiency of which enzyme?

Lactase

True or false: Fermentations cannot provide energy in the absence of oxygen

False. Thats exactly what it does!

Which process is used by humans to get energy from pyruvate in the absence of oxygen?

The Cori Cycle

Cori cycle reduces pyruvate from glycolysis to lactic acid, producing ________ for use in glycolysis

NAD+

True or false: NAD+ is needed to complete glycolysis, once all NAD+ reduced to NADH, glycolysis stops

True

How is NAD+ regenerated under oxygen debt?

The Cori Cycle

Lactate is converted to pyruvate through gluconeogenesis for another round of glycolysis in which tissue?

The Liver

Which tissue other than the liver shares the burden when the muscles are under oxygen debt?

Cardiac tissue

True of false: Cardiac cells can utilize lactate for use in the citric acid cycle and oxidative phosphorylation

True

Glucose synthesis occurs mostly in _________?

The Liver

What are sources of precursor molecules for gluconeogenesis?

amino acids (from muscle breakdown)
lactate (lactic acid)
glycerol (from fat breakdown)

The first enzyme of gluconeogenesis, pyruvate carboxylate, is located where?

In the mitochondria

The last enzyme of gluconeogenesis, glucose-6-phosphatatse is located where?

membrane bound in the endoplasmic reticulum

True or false: most enzymes of gluconeogenesis are located in the mitochondrial matrix?

False. Except for pyruvate carboxylate and glucose-6-phosphatase, all gluconeogenesis enzymes are cytoplasmic.

What is the product of pyruvate carboxylase?

Oxaloacetate

Oxaloacetate in gluconeogenesis is reduced to what?

Malate

What four enzymes are regulators of gluconeogenesis?

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

Gluconeogenesis and glycolysis are ___________ regulated

reciprocally

Which tissues have glucose 6-phosphatase?

Liver and kidneys

True or false: Most gluconeogenesis reactions end at glucose 6-phosphate and not glucose

True

Which enzyme and its associated components are only located in the endoplasmic reticulum.

glucose 6-phosphatase

How does the normal serum glucose level compare to GLUT1 and 3 Km present in all mammalian tissue?

it is about 4.8mM above Km

How does the normal serum glucose level compare to GLUT4 Km present in muscle and fat tissue?

the same

How does the normal serum glucose level compare to Km of GLUT2 present in liver and pancreatic beta-cells?

serum glucose level is below the Km

True or false: GLUT5 in the small intestine is primarily a fructose transporter

True

Under strict anaerobic conditions, the catabolism of one glucose molecule would yield a net of______________________?

2 ATP and 2 lactic acid molecules

Consider the conversion: alanine to lactic acid to glucose. This is an example of___________?

gluconeogenesis

Which of the following enzymes does not function in association with a membrane?
A. Permease
B. Na+/K+ ATPase
C. Adenylate cyclase
D. Phosphofructokinase
E. Coenzyme Q reductase

Phosphofructokinase

Insulin increases the activity of which of the following?
A. Enolase
B. Phosphorylase a
C. Phosphofructokinase
D. Glucose-6-phosphatase
E. Fructose 1-6 diphosphatase

Phosphofructokinase

ATP inhibits phosphofructokinase even though ATP is also a substrate for the enzyme. This phenomenon is an example of _______________?

allosteric inhibition