Carbohydrate Metabolism I: Glycolysis, Glycogen, Gluconeogenesis, and PPP

Question 1

GLUT2 & GLUT4

Answer 1

• 2 is a low affinity transporter in liver and pancreas

- 4 is in fat and muscle and responds to glucose concentration in peripheral blood (responsive to insulin)

Question 2

Net energy yield from glycolysis

Answer 2

2 NADH and 2 ATP

Question 3

Regulated glycolysis enzymes

Answer 3

• hexokinase/glucokinase
• PFK1
• Pyruvate Kinase

Question 4

Rate limiting step in glycolysis

Answer 4

conversion of F6P to F-1,6-bisP by PFK1

Question 5

Glycolysis in erythrocytes

Answer 5

RBCs can only use anaerobic glycolysis since they do not have mitochondria thus their net ATP production is 2 ATP

Question 6

What step in glycolysis makes NADH

Answer 6

conversion of Gly-3P to 1,3-BPG by Gly-3P dehydrogenase

Question 7

Key fermentation enzyme and fxn

Answer 7

Lactate dehydrogenase - oxidizes NADH to NAD+ which replenishes oxidized coenzyme for Gly-3P DHGase

Question 8

Cofactors and coenzymes required for PDH complex

Answer 8

Thiamine pyrophosphate, lipoic acid, CoA, FAD, and NAD+

Question 9

What are the reactants and products of PDH complex?

Answer 9

Reactants are pyruvate, NAD+ and CoA

Products are AcCoA, NADH, and NADH

Question 10

How is galactose trapped inside cell and linked into glycolysis?

Answer 10

• Trapped by phosphorylation via galactokinase

- Gal-1-P uridyltransferase then produces G-1-P which links it to glycolysis

Question 11

How is fructose trapped inside cell and linked to glycolysis?

Answer 11

• Trapped by phosphorylation via fructokinase (and smallm contribution from hexokinase)
• linked to glycolysis via aldolase B which produces DHAP and glyceraldehyde

Question 12

What is the structure of glycogen

Answer 12

Made up of a core protein of glycogenin with linear chains of glucose emanating out from the center connected via alpha-1,4 glycosidic links and branches connected via alpha-1,6 glycosidic links

Question 13

What are the 2 main enzymes of glycogenesis and their fxns?

Answer 13

1. Glycogen synthase - attaches glucose molecule from UDP-glucose to the growing glycogen chain forming an alpha-1,4 link in the process
2. Branching enzyme - creates branch by breaking alpha-1,4 links and moving a block of oligoglucose to another location in the glycogen granule which is then attached with an alpha-1,6 link

Question 14

What are the 2 main enzymes of glycogenolysis and their fxns?

Answer 14

1. Glycogen phosphorylase - removes glucose molecule from glycogen at the nonreducing end (end with free 4’OH) using a phosphate which breaks alpha-1,4 link and creates a G1P molecule
2. Debranching enzyme - removes alpha-1,4 link adjacent to branch and moves to end of chain and then hydrolyzes alpha-1,6 to release single glucose from former branch

Question 15

Under what physiological conditions does the body carry out gluconeogenesis?

Answer 15

when an individual has been fasting > 12h
in order for it to occur the hepatic and renal cells must have enough energy which requires sufficient fat stores to undergo Beta oxidation

Question 16

The liver maintains glucose levels in the blood during fasting through what two methods?

Answer 16

Gluconeogenesis and glycogenolysis

Question 17

What to organs carry out gluconeogenesis

Answer 17

Liver and kindeys

Question 18

Important substrates for gluconeogenesis

Answer 18

1. Gly-3-P (from stored fats or TAGs in adipose tissue)
2. Lactate (from anaerobic glycolysis)
3. Glucogenic aa’s (from muscle proteins)

Question 19

Glucose is converted into AcCoA, but AcCoA cannot be converted back into glucose… Since most FA’s are metabolized into AcCoA, they are usually not substrates of gluconeogenesis… What FA’s are a minor exception to this fact?

Answer 19

FA’s with an odd number of carbon atoms which yield a small amount of propionyl-CoA which is glucogenic can be used

Question 20

What enzymes convert substrates for gluconeogenesis into useable forms for this pathway?

Answer 20

1. Lactate into pyruvate via LDH
2. Gly-3-P into DHAP via Gly-3-P DHGase
3. Alanine into pyruvate via alanine aminotransferase

Question 21

4 unique and irreversible enzymes of gluconeogenesis and their fxns

Answer 21

1. Pyruvate carboxylase - converts pyruvate into OAA
2. PEP carboxykinase - converts OAA into PEP using GTP and releasing CO2
3. F-1,6-BisPase - converts F-1,6-BisP into F-6-P
4. G-6-Pase - converts G-6-P into glucose

Question 22

Why is pyruvate carboxylase a special enzyme in gluconeogenesis

Answer 22

it is the only mitochondrial enzyme of gluconeogenesis that must be activated by AcCoA from beta oxidation
its product, OAA, is unable to leave mtc and is reduced to malate via malate DHGase which can leave via the malate-aspartate shuttle for transport into the cytoplasm and oxidation back into OAA again

Question 23

How does AcCoA shift the metabolism of pyruvate?

Answer 23

1. inhibits PDH complex from undergoing TCA cycle when energy status of the cell is high
2. activates pyruvate carboxylase to induce gluconeogenesis when the energy status of the cell is low

** AcCoA for this regulation comes predominantly from
Beta-Ox… not glycolysis!

Question 24

What are the two major products of the pentose phosphate pathway and their functions

Answer 24

1. NADPH for lipid biosynthesis and other things

2. ribulose-5-P for nucleotide synthesis

Question 25

What is the rate limiting step of gluconeogenesis

Answer 25

F-1,6-BisPase conversion of F-1,6-BisP into F-6-P (reversal of what PFK1 does in glycolysis)

Question 26

What are the major functions of NADPH

Answer 26

1. Lipid biosynthesis (FA’s and cholesterol)
2. Bactericidal bleach formation in certain WBC’s
3. Maintenance of glutathione to protect against ROS

Question 27

How does glutathione protect against ROS and what are ROS’s?

Answer 27

ROS are free radical oxidative species in the body such as those from the product of H2O2 and OH that attack attack lipids such as those in the cell membrane which upon oxidation lose their fxn and can weaken the membrane causing cell lysis (especially true in RBC’s which contain high levels of O2, another ROS)

Glutathione is a reducing agent and thus can help reverse radical formation before damage is done to the cell

Question 28

Two parts of PPP

Answer 28

1. oxidative stage - G6P (from glycolysis) is converted into ribulose-5-P in a series of irreversible steps with the production of NADPH
2. reductive stage - ribulose-5-P is converted into an equibrilated pool of sugars for nucleotide biosynthesis in a series of reversible reactions. Some of these sugars include ribose-5-P, F-6-P, and Gly-3-P, the latter two which can be fed back into glycolysis

Question 29

What is the rate-limiting step of PPP

Answer 29

Glucose-6-phosphate dehydrogenase (G6P DHGase) in the oxidative phase

Question 30

what are some glycolytic intermediates that can be converted into pentoses and how?

Answer 30

F6P and Gly-3P can be converted into pentoses (without going through the G6P DHGase reaction) by interconversion through transketolases and transaldolases