Biochem--Glycogen Metabolism And Gluconeogenesis

Front 1

What are the tissues cells that primarily use glucose for energy?

Back 1

Brain: fatty acids cannot pass the blood-brain barrier
RBC's: don't have mitochondria
Kidney medulla, lens, cornea of eye, testes: poor in mitochondria
exercising muscle: short term high intensity exercise requires glucose

(blood glucose levels have to be maintained to supply substrate for tissues that primarily rely on glucose as an energy source!)

Front 2

What are the 3 main sources of glucose in the human body?

Back 2

-diet
-glycogen
-gluconeogenesis

Front 3

How are blood glucose levels maintained in the human body during fasting?

Back 3

SHORT TERM FASTING: maintained by degradation of liver glycogen (24 hours)

LONG TERM FASTING: maintained through gluconeogenesis by liver

Front 4

What is the structure of glycogen?

Back 4

-glucose polymer
-branched structure
-branches occur at every 8-10th glucose molecule

Front 5

How is liver and muscle glycogen utilized?

Back 5

Liver: maintenance of blood glucose levels during short term fasting

Muscle: provide energy to exercising muscle (muscle doesn't release glucose into circulation)

Front 6

What are the basic steps of glycogen synthesis?

Back 6

-glucose has to be converted to UDP-glucose to build glycogen
-initiation and elongation of glycogen chains (glycogenin, chains elongated by glycogen synthase)
-branch formation in glycogen (catalyzed by branching enzyme)

Front 7

What are the basic steps of glycogen degradation?

Back 7

GLYCOGENOLYSIS
-chain shortening (glycogen phosphorylase degrades it, glucose removed as glucose 1-P)
-removal of branches (debranching enzyme, it removes free glucose)

Front 8

Recognize metabolic diseases of glycogen degradation by associating with enzyme deficiencies and accumulated metabolites basic symptoms

Back 8

look at table on slides

Front 9

What are the allosteric regulators of glycogen metabolism?

Back 9

In the LIVER:
-glucose will (-) degrade glycogen metabolim
MUSCLE:
-when there is Ca and AMP in muscle, it would run the reaction because it needs energy

In both LIVER and MUSCLE
-Glucose 6-P will synthesize and degrades it

Front 10

What are the hormones that regulate glycogen metabolism in the liver and muscle?

Back 10

LIVER: glucagon (fasting), insulin (well-fed), epinephrine
MUSCLE: epinephrine, inculin
(glucagon does not affect muscle glycogen metabolism because fasting has little effect on muscle glycogen stores)

Front 11

How are the enzymes of glycogen metabolism regulated by phosphorylation/dephosphorylation?

Back 11

Glycogen <----> Glucose 1-phosphate

Insulin will dephosphorylate the reaction to make glycogen by activating protein phosphatase

Glucagon (cAMP) will phosphorylate it to make glucose 1-phosphate by activating phosphorylase kinase.

Front 12

What is the role of gluconeogenesis in the liver and kidney cortex?

Back 12

LIVER:
-it is responsible for maintaining blood glucose levels for the entire body

KIDNEY CORTEX:
-mainly provides glucose for kidney medulla but some glucose also gets into the systemic circulation

Front 13

What is the major gluconeogenic substrates?

Back 13

Lactate
glycerol (from triglycerides in adipose tissue)
glucogenic amino acids (alanine is the main one)

Front 14

Explain the glucose/alanine and Cori cycles in gluconeogenesis.

Back 14

GLUCOSE/ALANINE cycle
-glucose goes into the muscle from the bloodstream, then it runs through glycolysis making pyruvate.
]-pyruvate ---> alanine through transamination
-Alanine is then transported to the kiver ---> pyruvate, and through gluconeogenesis makes glucose again
-this glucose can then be used by muscles again and the cycle can continue (mainly muscle and intestine)

CORI Cycles (exercising muscle, RBCs and WBCs)
-pretty much same as G/A cycle but lactate is formed and goes into the blood to the liver.
-from there lactate goes through gluconeogenesis to for glucose

Front 15

List the steps of gluconeogenesis, which are not the reverse reactions of glycolysis.

Back 15

CONVERSION OF PYRUVATE TO PHOSPHOENOLPYRUVATE (3rd irrevers. step of glycolysis)
-pyruvate ---> oxaloacetate
-oxal. cannot cross mitochondrial membrane so it is converted to malate
-malate can then ---> oxaloactate in cytosol ---> PEP

DEPHOSPHORYLATION OF FRUCTOSE 1, 6-BISPHOSPHATE
-F 1, 6-bis is dephosphorylated by fructose 1, 6-bisphosphatase (regulatory steps of gluconeogenesis)
-opposite of PFK-1 regulation (PFK-2 becomes inactive, decreased inhibition of FBP-1, increasing rate of gluconeogenesis)

DEPHOSPHORYLATION OF GLUCOSE 6-PHOSPHATE
-glucose 6-phosphate --> glucose (using glucose 6-phosphatase--dephosphorylates)

Front 16

Calculate the ATP needed for producing a certain amount of glucose.

Back 16

For each synthesis of glucose molecules, gluconeogenesis requires 6 ATP molecules (4 ATP + 2 GTP)
-needs that many because there are 2 pyruvates (3 carbon) that are formed from the 1 glucose (6 carbon)

Front 17

Explain the regulation of gluconeogenesis and compare it to the regulation of glycolysis.

Back 17

Basically it works opposite of one another.
-at low glucose levels, the glucokinase is not active so glycolysis is inhibited and gluconeogenesis runs because you need more in the bloodstream

Front 18

What is Von Gierke Disease (type 1)?

Back 18

deficient enzyme: glucose 6-phosphatase
organs involved: hepatomegaly (fatty liver), renomegaly
blood metabolites:
- increased lactic acid, uric acid lipids
- decreased glucose during fasting

(growth retardation, delayed puberty)

Front 19

Pompe Disease (type 2)

Back 19

Enzyme: alpha (1-4)-glucosidase (lysosomal)
Organs: cardiomegaly
Blood metabolites: normal blood glucose
(general weak muscle tone)

Front 20

McArdle Syndrome (type 5)

Back 20

Enzyme: glycogen phosphorylase (skeletal muscle)
Organs: cramping of skeletal muscle after exercise
Blood metabolites: increased myoglobin (muscles are broken down), no increase in lactate after exercise
Urine metabolites: increased myoglobin

(temporary weakness after exercise)

Front 21

What are the main functions of glycogen in the liver and muscle?

Back 21

Liver: maintenance of BLOOD GLUCOSE levels during short term fasting (gluconeogenesis by liver for long term fasting)
Muscle: provides energy to exercising muscles

Front 22

What is needed in order to build complex carbohydrates from monosaccharides?

Back 22

The building blocks must be nucleotide activated!
-glucose needs to be converted to UDP-glucose to build glycogen

Front 23

What is transaldolase?

Back 23

transfers 3 carbon units

Front 24

transketolase?

Back 24

transfers 2 carbon units
-requires thiamine pyrophosphate (vit B1) as a cofactor

patients' vitamin B1 (thiamine) levels are measured by the activity of red blood cell transketolase

Front 25

What is NADPH's role in nitric oxide production?

Back 25

-vasodilator: relaxes vascular smooth muscle cells
-anticoagulant: inhibits platelet aggregation
-neurotransmitter: in brain
-antibactericidal: reats with superoxide and forms highly reactive radicals that kill pathogens

Front 26

WHAT is NADPH's role in phagocytosis?

Back 26

-NADPH oxidase generates superoxide that destroys bacteria (needs NADPH)

Front 27

What is Chronic granulomatous disease?

Back 27

-NADPH oxidase is deficient
-can't kill off bacteria because superoxides cannot destroy bacteria
-nodular areas that sequester bacteria

Front 28

What is glutathione?

Back 28

-tripeptide
-detoxifies H2O2 by glutathione peroxidase
-in the process, glutathione gets oxidized
-glutathione (oxidized) has to be reduced (by glutathione reductase) to be able to neutralize another H2O2 molecule
-glutathione reductase requires NADPH to reduce glutathione

(process is primary defense mechanism of red blood cells against oxidative damage)

Front 29

What happens when there is a glucose 6-phosphate dehydrogenase deficiency?

Back 29

-acute hemolytic anemia
(increased oxidative stress because NADPH cannot be made to remove the H2O2)
-fatgue, pallor, shortness of breath
-high bilirubin levels (increased degradation of hemoglobin--hemolysis, more oxidative stress)
-high reticulocyte count (more immature RBC's produced by bone marrow)

G6PD deficiency confers resistance to malaria infections

Front 30

What is lactose made of?

Back 30

galactose and glucose

Front 31

Classic Galactosemia

Back 31

uridyltransferase deficiency
-causes galactosemia, galctosuria, vomiting, diarrhea, jaundice
-accumulation of galactose 1-phosphate and galactitol in nerve, lens, liver, and kidney tissues
-causes liver damage, severe mental retardation, and cataracts
-THERAPY: removal of galactose (and therefore lactose) from diet

Front 32

Lactose synthesis

Back 32

2 proteins catalyze lactose synthesis
-UDP-galactose + glucose-->lactose + UDP

Front 33

What is fructose made of?

Back 33

sucrose and glucose

Front 34

Aldolase A and Aldolase B

Back 34

Aldolase A in glycolysis can make dihydroxyacetone P and glyceraldehyde 3-P--->pyruvate for energy production

Aldolase B (during 2nd step of fructose metabolism) helps make glyceraldehyde--> phosphoglyceride synthesis/triacylglycerol synthesis) and dihydroxyacetone-P (same as aldolase A to go down glycolysis or gluconeogenesis)

Front 35

disorder of fructose metabolism
-hereditary fructose intolerance
(fructose poisoning)

Back 35

absence of aldolase B: leads to intracellular trapping of fructose 1-P and LOW ATP
-causes severe hypoglycemia, vomiting, jaundice, hemorrhage, hepatomegaly
-therapy: removal of fructose and sucrose from diet