Biochem--Glycolysis And Some Glycogen Metabolism

Front 1

What are the different pathways of glucose utilization by cells?

Back 1

-Glycolysis (energy production)
-Glycogen synthesis (storage mainly in liver and skeletal muscle)
-Conversion to UDP-glucose (glycosaminoglycan, glycoprotein, glycolipid, lactose synthesis)
-Pentose-phosphate pathway (NADPH and ribose-5-phosphate production)
-Conversion to sorbitol (fructose synthesis, mainly in seminal vesicles)

Front 2

How is glucose taken up by different cells?

Back 2

NA+ DEPENDENT GLUCOSE TRANSPORTER (SGLT)
-uptake by intestinal epithelial cells from the digestive tract

NA+ INDEPENDENT GLUCOSE TRANSPORTERS (GLUT)
-tissue specific
-GLUT-2: main bidirectional transporter in LIVER, KIDNEY, PANCREAS
-GLUT-4: specific for muscle and adipose tissue
-GLUT-4: only INSULIN-REGULATED GLUCOSE TRANSPORTER

Front 3

Explain the glucose conversion to sorbitol and the importance of this process in normal physiology and in diabetes.

Back 3

-it can be performed in many tissues
PHYSIOLOGY IMPORTANT (seminal vesicles)
-sorbitol converted to fructose
-fructose secreted into seminal fluid
-sperm cells use fructose as main energy source

DIABETES
-hyperglycemia: causes excess sorbitol production in lens, retina, nerve, and kidney cells
-cells are inefficient to convert sorbitol to fructose
-sorbitol accumulates in cells, attracts lots of water causing swelling of the cells
-leads to complications in diabetes (cataracts, retinopathy, nephropathy, peripheral neuropathy)

Front 4

What is the difference between aerobic and anaerobic glycolysis?

Back 4

difference is how NADH is oxidized back to NAD+
AEROBIC: uses oxygen
-oxidative phosphorylation in mitochondria
ANAEROBIC: no oxygen
-lactate dehydrogenase in cytosol

Front 5

Calculate the ATP and NADH yields of glycolysis from a given amount of glucose.

Back 5

Glucose to pyruvate
Aerobic: first phosphorylation step you use 2 ATP to run it
-energy generation phase produces 4 ATP (2 for each substrate)
NET: 2 ATP
2 NAD+ makes 2 NADH

(anaerobic glycolysis there is no net change in NAD+ and NADH

Front 6

What are the metabolites of the glycolytic pathway?

Back 6

-glucose 6-P
-fructose 6-P
-fructose 1, 6-bis-P
-glyceraldehyde 3-P
-1,3-bis-Phosphoglycerate
-3-Phosphoglycerate
-2-Phosphoglycerate
-Phosphoenlpyruvate
-Pyruvate

Front 7

What are the 3 irreversible steps of glycolysis?

Back 7

1. Glucose --> Glucose 6-P (uses ATP
2. Fructose 6-P --> Fructose 1,6-bis-P (uses ATP)
3. Phosphoenolpyruvate --> Pyruvate (produces ATP)

Front 8

Describe the four pathways that metabolize pyruvate.

Back 8

LACTATE
-anaerobic glycolysis (lactate dehyrogenase)
OXALOACETATE
-gluconeogenesis, TCA cycle (pyruvate carboxylase)
ACETYL COA
-TCA cycle, fatty acid synthesis (pyruvate dehydrogenase)
ACETALDEHYDE
-only in microorganism (not in the human body) (pyruvate decarboxylase) ---when making alcohol

Front 9

What are the consequences of pyruvate kinase deficiency?

Back 9

It causes hemolytic anemia:
-RBC's do not have mitochondria
-ATP production is dependent on glycolysis
-ATP is necessary for plasma membrane pumps to maintain flexibility of RBC's
-with no ATP, RBC's will have abnormal shape and are destroyed by macrophages

Front 10

What are the physiological and pathological conditions that lead to lactic acidosis?

Back 10

1. in tissues with little vascularization or in cells that have little/no mitochondria
(cornea & lens of eye, kidney medulla, WBC & RBC's
2. during strenuous exercise in skeletal muscle
-increased NADH exceeds oxidative capacity of respiratory chain ---> NADH used by lactate dehydrogenase
(causing accumulation of lactic acid in muscle, causing cramps)
3. during collapse of circulatory system (blocking O2 to get into muscles)
-myocardial infarction, pulmonary embolism, uncontrolled hemorrhage, shock)
-with no O2, cells use anaerobic glycolysis, increasing lactic acid

==> lactic acidosis

Front 11

What are the major regulatory steps and regulated enzymes of glycolysis?

Back 11

Glucose --> Glucose 6-P (glucokinase)
-insulin activated, glucagon deactivates

Fructose 6-P --> Fructose 1, 6-bis (PFK)
-insulin activates, glucagon deactivates

PEP --> pyruvate (pyruvate kinase)
-insulin activates, glucagon deactivates

Insulin/glucagon ratio regulates activity of PFK-1 through allosteric effect of fructose 2, 6-bisphosphate
-insulin/glucagon ratio regulates activity of pyruvate kinase through deposphorylation and phosphorylation
-insulin and glucagon levels regulate synthesis of key enzymes of glycolysis (transcription)

Front 12

What is the difference between hexokinase and glucokinase? How are they regulated?

Back 12

Hexokinase
-most tissues
-lower Vmax
-lower Km
-regulated by glucose-6-P
-main utilization in FASTING STATE

Glucokinase:
-liver, pancreas
-higher Vmax
-higher Km
-regulated by glucose (+) fructose-6-P (-)
-main utilization in FED STATE

Front 13

What are the basics of signaling by insulin and glucagon inside the cell?

Back 13

Insulin (anabolic) increases insulin after a meal
-produced by pancrease B cells in the FED STATE
-stimulates glucose uptake, glycolysis, and glycogen synthesis
-downregulates glycogen degradation and gluconeogenesis (inhibits because it has enough glucose in circulation...doesn't need to make any)

Glucagon (catabolic)
-produced by pancreas a cells in FASTING STATE
-stimulates glycogen degradation and gluconeogenesis in liver (needs to produce because none is coming from food)
-downregulates glycogen synthesis, glycolysis in the liver (inhibits)

Front 14

How does insulin/glucagon ratio regulate glycolysis in the liver?

Back 14

Insulin initiates the dephosphorylation of metabolic enzymes
-if there is a lot of insulin, glycolysis runs because it already has enough glucose in circulation so it makes energy to use else where

Glucagon: phosphorylation of metabolic enzymes
-inhibits glycolysis in the liver because it needs glucose in circulation

Front 15

What is the mechanism of phosphofructokinase-1 regulation?

Back 15

indirectly regulates PFK-1 through synthesis of fructose 2, 6-bisphosphate (allosteric activator of PFK-1)
-with high insulin/glucagon ratio --> increased F-2, 6-P levels --> more active PFK-1
-with low insulin/glucagon ratio --> reduced F-2, 6-P levels --> less active PFK-1

Front 16

What is the mechanism of pyruvate kinase regulation?

Back 16

fructose 1,6-bisphosphate --> + regulation
glucagon (low blood glucose) --> - regulation

--glucagon initiates a signaling pathway that phosphorylates (deactivates) pyruvate kinase by protein kinase A
-phosphoprotein phosphatase can dephophorylate (reactivate) pyruvate kinase (induced by insulin)

Front 17

What hormones have an effect on the liver?

Back 17

glucagon during fasting
insulin during well fed state
epinephrine

Front 18

what hormones have an effect on muscle?

Back 18

insulin and epinephrine

Front 19

What effect on enzymes of glycogen metabolism do each of the three hormones have?

Back 19

Glucagon: phosphorylates the enzymes and degrades glycogen metabolism
(during fasting, you want glucose to be made so it activates degradation of glycogen)
-insulin: dephosphorylates protein phosphatase and synthesizes glycogen metabolism
(insulin means you have enough glucose in the blood, so it will make more glycogen for storage and inhibit glycogen degradation)
-epinephrine: phosphorylates the enzymes and degrades glycogen metabolism
(same effect as glucagon)

Front 20

How fast is liver glycogen stores depletes?

Back 20

within 24 hours of fasting

it is responsible for maintaining blood glucose levels for the entire body

Front 21

What are the 2 energy-producing phases in glycolysis?

Back 21

1,3 bis phosphoglycerate to 2,3-bisphosphoglycerate
phosphoenolpyruvate (PEP) to pyruvate

(there are 2 of each in glycolysis so combined they would form 4 ATP)

Front 22

What does pyruvate kinase deficiency cause?

Back 22

- Red blood cells (RBCs) do not have mitochondria
- ATP production is strictly dependent on glycolysis
- ATP is necessary for plasma membrane pumps to maintain the flexibility the RBCs.
- In the absence of ATP red blood cells will have an abnormal shape and are destroyed by macrophages.