Lecture 21 - Food sources for energy generation and anabolism

Question 1

Gluconeogenesis: what is it, where does it mainly occur, what does it do, what is the reaction, and what is the difference with glycolysis?

Answer 1

Synthesis of glucose from noncarbohydrate precursors, ie lactate and alanine, via pyruvate

Liver is major site, small amount in kidney

Maintains glucose levels in blood, provides energy to brain and muscle

2Pyruvate + 2NADH + 4ATP + 2GTP + 6H₂O + 2H⁺ → Glucose + 2NAD⁺ + 4ADP + 2GDP + 6Pᵢ

• The 3 irreversible steps in glycolysis require
  separate enzymes for gluconeogenesis
• The enzymes for the reversible steps are the same
• Requires much more free energy (6ATP/GTP) than glycolysis (2ATP)

Question 2

Glycolysis pathway: the steps

Answer 2

(I) Glucose + hexokinase/glucokinase -> glucose-6-phosphate

(R) G6P + G6P isomerase -> Fructose-6-phosphate

(I) F6P + Phosphofructokinase-1 -> Fructose-1,6-bisphosphate

(R) F1,6BP + aldolase -> Glyceraldehyde-3-phosphate / dihidroxyacetone phosphate

Question 3

Glycolysis pathway: the steps

Answer 3

(R) Glyceraldehyde-3-phosphate / dihidroxyacetone phosphate + aldolase -> Fructose-1,6-bisphosphate

(I) F16BP + fructose-1,6-bisphosphatase -> Fructose-6-phosphate

(R) F6P + G6P isomerase -> Glucose-6-phosphate

(I) G6P + Glucose-6-phosphatase -> glucose

Question 4

more bs

Question 5

Pyruvate carboxylase: what is it, what does it do, what is the reaction it catalyses, what does it need, and what is it activated by?

Answer 5

Important enzyme at the start of gluconeogenesis

Catalyzes a metabolically irreversible reaction, which occurs in the mitochondrial matrix

Pyruvate + CO₂ + ATP → oxaloacetate + ADP + Pᵢ

Requires a prosthetic group - biotin

Allosterically activated by acetyl CoA - accumulation signals abundant energy and directs pyruvate to oxaloacetate for gluconeogenesis

Question 6

Biotin: what is it and what does it do?

Answer 6

A prosthetic group that is covalently attached to pyruvate carboxylase (through a Lys side chain)

Carries activated CO2 (carboxybiotin)

Question 7

Glucose storage in organisms: what types of storage are there, what type of branching is there, and how is glucose stored in vertebrates?

Answer 7

Glucose is stored as starch (plants) or glycogen (animals)

Polymers of glucose can have different branching - α(1,4), or α(1,6)

Glycogen is stored in cytosolic granules in the liver and muscle cells of vertebrates

Question 8

Glycogenolysis - Glycogen breakdown - phosphoglucomutase: how it all works

Answer 8

Glycogenolysis - degradation of glycogen

Glycogen breakdown → glucose-1-phosphate (G1P)
Converted to glucose-6-phosphate (G6P)

phosphoglucomutase → glycolysis → energy (ATP)

Question 9

Glycogen structure

Answer 9

Glycogenin at the centre (a protein promoting glycogen synthesis) surrounded by many branched chains of glucose

Question 10

Glycogen: what is it used for and what key features are there?

Answer 10

Quick source of glucose for sudden demand of
energy which can provide energy in the absence of oxygen (anaerobic activity)

• Controlled release of glucose from glycogen in
  the liver maintains blood glucose concentration
  between meals, sleeping, etc.
• Less reduced than fatty acids, not so rich in
  energy

Question 11

Glycogen degradation: what enzyme is used and what is the reaction?

Answer 11

Glycogen phosphorylase catalyzes the sequential removal of glucose residues

Stops at 4 residues from a branch point - The resulting “limit dextrin” is remodelled by two enzymes: a transferase shifts three glucose from one outer branch to another and the glycogen-debranching enzyme α-1,6-glucosidase removes the branched glucose and leaves an elongated unbranched chain (which can be further degraded by glycogen phosphorylase

Glycogen (n residues) + Pᵢ ⇄ glucose-1-phosphate + Glycogen (n – 1 residues)

Question 12

Phosphoglucmutase: what does it do?

Answer 12

Easily converts glucose-1-phosphate (G1P) to glucose-6-phosphate (G6P)

Question 13

Glycogen formation

Answer 13

Cellular glucose is converted to G6P by glucokinase
in the liver cells. Energy is spent
Glucose + ATP → glucose-6-phosphate + ADP
Additional steps are required to incorporate one
G6P into glycogen. More energy is spent
Glucose-6-phosphate → glucose-1-phosphate
Glucose-1-phosphate + UTP → UDP-glucose +PPi

Question 14

UDP-glucose formation

Answer 14

Catalysed by UDP-glucose pyrophosphorylase

Liberates the outer two phosphate groups
from UTP as PPi (pyrophosphate)
UDP glucose is the activated form of glucose
for glycogen synthesis

Question 15

UDP-glucose

Answer 15

UTP is energetically
equivalent to ATP
UDP + ATP ⇄ UTP + ADP
Overall, 2ATP are spent to incorporate one
dietary glucose into glycogen: one from
glucokinase reaction, one to form UDP-glucose