UNIT 4: REVIEW OF INTERMEDIARY METABOLISM Flashcards
Match the definitions with the terms:
1. “breakdown of stored glycogen to release glucose molecules”
2. “production of glucose from non-sugar substrates (lactate, glycerol, a.a.)”
3.
“glucose forms NADPH and ribose sugars”
4. “oxidation of glucose to pyruvate”
5. “production of glycogen granules from glucose”
6. “oxidize acetyl CoA to CO2”
- Glycogenolysis
- Gluconeogenesis
- Hexose monophosphate shunt = pentose phosphate pathway
- Glycolysis
- Glycogenesis
- Tricarboxylic acid cycle
What are 3 fates of glucose?
Depending on the cell:
- glycogen
- glycolysis (to produce acetylCoA and fuel TCA cycle)
- pentose phosphates (for biogenesis)
Glucagon is made in the ____ whereas Insulin is made in the _____.
Glucagon: alpha cells
Insulin: beta cells
…of the islets of pancreas
What tissues make glycogen?
What is the content of glycogen in each tissue?
liver and muscle
- liver stores 10% of wet weight
- muscle 1%
BUT 75% of glycogen is in muscle (because more muscle
What triggers glycogen synthesis?
Presence of G6P (accumulation)
What 2 enzymes are involved in glycogen synthesis (glycogenesis)?
Hexokinase and Glucokinase
What is the role of hexokinase?
Hexokinase is in the muscle
- allosterically inhibited by high glucose 6
phosphate
- free glucose builds up inside muscle
- since hexokinase cannot convert glucose to G6P
- stops glucose being transferred from blood to muscle (since build up of glucose in muscle)
What is the role of glucokinase?
in the liver
- NOT inhibited by G6P, liver cells continue to phosphorylate free glucose (from blood stream)to G6P
- build up of G6P, satisfies hexose monophosphate shunt, to process G6P to acetyl CoA (glycolysis)
- removed from liver as VLDL particles made de novo fatty acids and triglycerides
The muscle takes up glucose _____ , while liver takes up glucose _____.
Muscle: based on needs
Liver: continuously/ongoing removing glucose from blood stream
How many high energy phosphates are expended per glucose to be stored as glycogen?
2 Phosphates
- ATP used. Glucose (in blood) —> G6P in muscle (via hexokianse) or liver (glucokinase)
- Glucose 1 Phosphate reacts with UTP to form UDP-glucose (Pi released). UDP-glucose bond can release enough energy to add glucose to form glycogen chain.
What protein does glycogen synthesis start on?
glycogenin
What’s the difference between a-1-4 and a-1-6 links?
Glycogen links.
a-1-4 chain is linear
a-1-6 chain is at branched points.
(too much branching = increase volume = very dense sphere = glycogen granule)
What happens to glycogen in glycogenolysis?
- glycogen is converted to G1P in liver or muscle, then G6P
- G6P then converts to glucose in blood OR lactate in blood to liver
What is the fate of G6P in glycogenolysis?
Liver: G6P released to blood stream because of glucose6phosphatase in the SER
Muscle: G6P is fully oxidized to CO2 or converted to lactate
What happens to lactate that comes from the muscle from glycogenolysis?
Lactate is taken up by liver and converted back to glucose. (Therefore, muscle plays an indirect role in contributing to blood glucose)
Substrate level phosphorylation occurs in:
a. glycolysis
b. TCA
c. ETC
Substrate level phosphorylation occurs in both a. glycolysis and b. TCA
ETC is oxidative phosphorylation
What are the products of glycolysis?
- Net: 2ATP
- 2 pyruvate
- 2 NADH
When does pyruvate form acetyl-coa and how?
- Aerobic conditions: in the presence of O2
- pyruvate dehydrogenase activity
What causes muscle pain in anaerobic conditions?
Lactate production increases H+ ions that increase metabolic acidosis and decreases muscle contractility.
Under anaerobic conditions, NAD+ is regenerated by…
converting pyruvate to lactate
Under anaerobic conditions how is glucose regenerated?
lactate is sent to the liver and converted to glucose via gluconeogenesis (Cori Cycle)
Is the Cori Cycle energy producing or energy using?
Energy using.
In the liver, Lactate to Glucose (gluconeogenesis)
- requires 6ATP per 2 molecules of lactate to form 1 glucose
- 1 glucose produces 2 ATP
- not sustainable under intense exercise
Where does the hexose monophosphate shuttle take place?
Cytosol
- uses G6P as substrate
What are the two possible routes of the HMPS?
- oxidative phase
- non-oxidative phase
What do each of the two phases of HMPS produce?
Oxidative phase: produces ribulose-5-phosphate
Non-oxidative phase: ribose-
In the oxidative phase, what is the purpose of the redox couple in HMPS?
HMPS is the major pathway that maintains the reduced state NADPH in the NADP+/NADPH.
- reducing power is used for anabolism and oxidant defense
_____ acts as a strong reducing agent for oxidant defense.
NADPH
- anabolic metabolism
How is pyruvate converted to acetyl CoA?
Pyruvate Dehydrogenation via pyruvate dehydrogenase complex
Pyruvate Dehydrogenation is important because it converts pyruvate (3C) to acetyl CoA (2C). The type of metabolism changes from ____ to _____.
Glucogenic to Ketogenic
What are the 4 cofoactors involved in pyruvate dehydrogenation?
- Pantothenic acid as CoA
- Thiamine as TPP
- Niacin as NAD+
- Riboflavin as FAD
What are the products of pyruvate dehydrogenation?
- acetyl CoA
- CO2
- NADH
What are the 2 TCA inputs?
- acetyl CoA
- oxaloacetate
From 6C citrate to 4C succinyl-CoA how many electrons are captured?
4 electrons as 2 NADH
- C released as CO2
From 4C succinyl coA what happens as it is reverted back to oxaloacetate?
- GTP
- FADH2
- NADH
produced
TCA cycle is also the starting place for ______
gluconeogenesis or de novo synthesis of glucose
What is the molecule that is gluconeogenic/glucogenic?
malate
- if malate can be transported out of mitochondria, then all other intermediaries can be removed
Compare and contrast Glucogenic vs Ketogenic molecules in TCA.
Glucogenic: converted to TCA intermediate, removed when forming malate converted to glucose
Ketogenic: elongates existing intermediate but does not produce new intermediates and does not produce glucose
de novo synthesis of glucose from non-glucose precursors is called
Gluconeogenesis
Where does gluconeogenesis occur?
in the liver
start: mitochondria
end: cytosol
(reverse glycolysis)
What molecules can be the starting point for gluconeogenesis?
any metabolite that can enter TCA as a new intermediate
- alpha keto acids (pyruvate, glutamate, oxaloacetate)
- lactate
- glycerol
What happens to malate when it leaves the TCA cycle?
- Malate leaves the mitochondria
- Oxaloacetate in cytosol
- Oxaloacetate converted to PEP and reverse glycolysis
Why can’t ketogenic molecules be glucogenic?
acetyl coA only elongates the TCA cycle, it does not provide extra TCA intermediates
