Carbohydrate Metabolism

Question 1

Can glucose cross cell membrane, why?

Answer 1

No, it is too large and polar to be able to cross. It therefore requires the use of GLUTs (glucose transporters) that are located on the cell membrane or special case in a GLUT vesicle.

Question 2

GLUT1

Answer 2

ubiquitous (found everywhere), high affinity (low Km) for glucose, used mainly in RBCs and brain. Facilitated diffusion.

Question 3

GLUT2

Answer 3

Low affinity (high Km) for glucose, main transporter in liver. In a fed state, there is a surplus of glucose going through the liver, therefore the affinity of GLUT2 doesn’t have to be that high. Facilitated diffusion

Question 4

GLUT3

Answer 4

Main glucose transport in neurons, also has a high affinity (low Km) for glucose. Facilitated diffusion

Question 5

GLUT4

Answer 5

Glucose transporter present in skeletal muscle, heart and adipose tissue. This transporter is INSULIN DEPENDENT/regulated by insulin. Facilitated diffusion. Found in vesicles within cytosol of cell. When insulin binds to a surface receptor, it signals the GLUT4 vesicle to fuse with the plasma membrane, now creating channels available for glucose uptake.

Fed state > Insulin released > GLUT4 binds to membrane > glucose uptake.

Question 6

GLUT5

Answer 6

Transports glucose and fructose through the cell membranes. Facilitated diffusion

Question 7

Glycolysis products

Answer 7

anaerobically: 2 pyruvate, 2 NADH, 2 ATP&raquo_space; if continue 2 pyruvate are reduced to 2 lactate (muscle cells during exercise or red blood cells).
aerobically: pyruvate can be completely oxidized, or intermediates can go to other pathways.

Question 8

three phases of glycolysis

Answer 8

1) investment: includes first three enzyme catalyzed reactions in glycolysis, uses 2 ATP.
2) Splitting: in two rxns the split of 1 6C molecule to 2 3C
3) Payoff: 4 ATP produced, 2 NADP produced.

Question 9

What step of glycolysis traps glucose inside the cell

Answer 9

The first rxn in glycolysis phosphorylates glucose to G6P, which “traps” it inside the cell. All cells use HEXOKINASE to catalyze this rxn. The liver and pancreatic beta cells use GLUCOKINASE to catalyze this phosphorylation. This is a regulatory step

Question 10

First regulatory step of glycolysis and what regulates it

Answer 10

The first regulatory step of glycolysis is the first rxn in glycolysis. Hexokinase or glucokinase use 1 ATP to phosphorylate glucose to G6P. G6P inhibit this step (feedback inhibition), Glucagon inhibits (excess glucose, stop making energy), Fructose 6-P inhibits, Glucose fructose 1-P and Insulin (fed state, make energy from food) activate this pathway. Hexokinase has high affinity for glucose, glucokinase has low affinity > mostly used after eating when glucose levels are elevated so affinity doesn’t have to be very high

Question 11

Isozymes

Answer 11

Enzymes with different structures, but the same function.

Question 12

Rate limiting step of glycolysis, the enzyme of this step and regulators

Answer 12

The third rxn phosphorylates F6P to F1,6BP through the enzyme PHOSPHOFRUCTOKINASE-1. PFK-1 is positively regulated (continue through glycolysis) via AMP (more ATP needs to be generated – hungry) and F2,6BP (product of side/parallel rxn) and high insulin/low glucagon (fed state). PFK is negatively regulated (slow/stop glycolysis) via ATP (have enough energy) or citrate (intermediate of TCA cycle).

Question 13

glycolysis step that produces NADH

Answer 13

the 6th rxn of glycolysis converts G3P to 1,3BPG by using glyceralaldehyde 3-P dehydrogenase to reduce NAD+ to NADH (makes 2 NADH since theres 2 G3P).

Question 14

Last regulatory step of glycolysis, enzyme and how it is regulated

Answer 14

The last rxn in glycolysis converts phosphoenolpyruvate (PEP) to pyruvate via PYRUVATE KINASE. Insulin and Fructose-1,6BP positively regulate PK (increase activity, has glucose, wants to make energy). Glucagon, ATP and ALANINE negatively regulate PK (has enough energy stored, slow glycolysis and PEP enters gluconeogenesis).

Question 15

Hexokinase/glucokinase: compare

Answer 15

hexo: located everywhere, low Km, high affinity, low Vmax, glucose and other intermediates can be substrate, inhibited by G6P. glucokinase: located in liver and pancreatic beta, high Km, low affinity, high Vmax, glucose in the only substrate, not inhibited by G6P (but by glucagon)

Question 16

Fed state ??????

and opposite is hungry (glucagon)

Answer 16

high insulin, stimulates protein phosphatase which dephosphorylates PK making it active allowing it to phosphorylate PEP to pyruvate.

Question 17

G6P use in pathways other than glycolysis

Answer 17

Pentose phosphate pathway&raquo_space; makes ribose for DNA/RNA and NADPH for those pathways, eventually used in galactose metabolism, glycogen synthesis

Question 18

Pyruvate use in pathways other than glycolysis

Answer 18

transformed into oxaloacetate which is used in gluconeogenesis

converted to alanine for gluconeogenesis or protein synthesis

oxidized to acetly CoA and CO2 in TCA

reduced to lactate&raquo_space; Cori cycle

Question 19

glycolytic enzyme disorders often result in…

Answer 19

ineffective glycolysis = hemolytic anemia

Question 20

Causes of type 2 diabetes

Answer 20

enzyme mutations, unable to convert proinsulin to insulin, defective insulin receptor, pancreatitis, pancreatic carcinoma

Question 21

Tarui Disease

Answer 21

GSD VII: PFK-1 deficient > exercise induced muscle cramps/weakness, hemolytic anemia, jaundice,

Question 22

Gluconeogenesis

Answer 22

creates glucose from carbohydrates (pyruvate) in liver, kidney and SI when blood glucose levels are low and glycogen stores are depleted. Not direct reversal of glycolysis. Uses lactate, AA and glycerol as precursors. Bypasses irreversible steps of glycolysis using different enzymes.

Would chose to breakdown 1) glycogen stores/lactate/other carbs(galactose/fructose) 2) fat/glycerol 3) proteins/alanine

Question 23

glycolysis vs gluconeogenesis

Answer 23

gluconeogenesis uses: pyruvate carboxylase (PC), phosphoenolpyruvate carboxylkinase (PEPCK), F1,6BPhatase, G6Phatase

Question 24

PC enzyme gluconeogenesis

Answer 24

converts pyruvate to oxaloacetate so it can pass from inner mitochondrial space to cytosol. it is found on mito membrane. OAA is converted to malate in mito, malate transferred through the membrane via malate shuttle and reoxidized to OAA in cytosol. Pyruvate carboxylase uses biotin cofactor.

Question 25

Rate determining step of gluconeogenesis

Answer 25

converting F1,6BP to fructose 6P via FRUCTOSE 1,6-BISPHOSPHATASE. this enzyme is activated by cortisol and citrate (TCA intermediate). Inhibited by AMP and F26BP

Question 26

Glucose 6-phosphatase location and function

Answer 26

Located on lumen of ER, the G6Ptase converts G6P to glucose. G6P transported into ER and converted to glucose which is then transported into cytosol by GLUT 7

Question 27

GLUT 7

Answer 27

on ER lumen and transports glucose from lumen into cytosol in final step of gluconeogenesis

Question 28

Cori Cycle

Answer 28

in RBC and exercising muscle: moves lactate (produced by anaerobic glycolysis) into blood supply and then into liver for gluconeogenesis

Question 29

Fructose-1,6-bisphosphatase deficiency and its results on gluconeogenesis

Answer 29

similar to Tarui, but for gluconeogenesis. presents infancy. hypoglycemia, lactic acidosis, ketosis, apnea

Question 30

Von Gierke disease

Answer 30

GSD1a: glucose 6 phosphatase deficiency = can’t take final phosphate of of G6P in gluconeogenesis so unable to produce free glucose. Hepatomegaly, lyperlipidemia,

Question 31

GLUT 2 mutation

Answer 31

Fanconi-Bickel syndrome: can’t uptake glucose, fructose or galactose. Autosomal recessive disorder leads to hepatomegaly, resistant rickets. Treated with a special diet.

Question 32

Polyol Pathway

Answer 32

converts glucose to fructose via sorbitol intermediate. Cells without sorbitol dehydrogenase will accumulate sorbitol&raquo_space; water influx&raquo_space; swelling&raquo_space; cataracts

Question 33

Fructose metabolism

Answer 33

Doesn’t rely on PFK-1 so the rate determining step of glycolysis is skipped&raquo_space; faster metabolism&raquo_space; easier converted into fat&raquo_space; less healthy

Question 34

Galactose metabolism

Answer 34

GALT (glucose 1P uridyltransferase) is the rate limiting step

Question 35

GALT deficiency

Answer 35

glucose 1P uridyltransferase: galactitol accumulates&raquo_space; liver failure/sepsis/bleding

Question 36

PPP (pentose phosphate pathway)

Answer 36

the purpose is to create ribose used in DNR/RNA and NADPH used for biosynthesis. occurs in cytosol. Has an oxidative and nonoxidative phase.

Oxidative: G6P dehydrogenase (RATE LIMITING STEP) G6PD deficiency results in hemolytic anemia

non-oxidative: ribose is creates from ribulose and an isomerase. other glycolysis/gluconeogenesis metabolites are also created. Reversible reactions.

Question 37

What is glycogen

Answer 37

large glucose storage molecules when excess glucose in in body. has a 1,4 glycosidic bonds between linear sections and a1,6 glycosidic bonds at branch points. connected to a protein primer/glycogenin at the reducing end. non-reducing ends are added glucose at C4-OH

Question 38

where is glycogen stored

Answer 38

in the liver and muscle as granules (enzymes necessary + glycogen)

liver glycogen regulates BLOOD glucose

Muscle glycogen provides fuel for physical activity

Question 39

glycogenesis

Answer 39

process of making and extending glycogen molecules from glucose units.

glucose still trapped in cell by phosphorylating to G6P > G1P > UDP-glucose

Question 40

rate determining step of glycogenesis

Answer 40

GLYCOGEN SYNTHASE transfers glucose from UDP-glucose to the non-reducing (4C-OH of glucose) by forming a1,4 glycosidic bond

Question 41

How does glycogen branch

Answer 41

GLYCOSYL 4:6 TRANSFERASE breaks linear 11 glucose chain and attaches a 7 glucose chain to the 4th glucose away from previous branch or core protein.

Question 42

glycogenolysis

Answer 42

Rate limiting step is GLYCOGEN PHOSPHORYLASE which cleaves glucose residues until within 4 glucoses from branch point.

Question 43

Debranching glycogen

Answer 43

the Debranching enzyme releases the glucoses of the branch until the last one until glucosidase cuts the final glucose off the branch leaving a new linear glycogen chain to be degraded by GLYCOGEN PHOSPHORYLASE

Question 44

regulation of Glycogen Synthase

Answer 44

dephosphorylated is the active form and phosphorylated is the inactive form

Question 45

regulation of Glycogen Phosphorylase

Answer 45

phosphorylated is the active form and dephosphorylated is the inactive form