NAD+ Production Pathways and Ageing

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Questions and Answers

What are the three main pathways through which NAD+ is produced in mammalian cells?

The NAD+ salvage pathway, the de novo biosynthesis pathway, and the Preiss-Handler pathway

What is the consequence of a decline in NAD+ levels towards NADH in ageing?

Metabolic alterations and age-related immune changes

What is the potential therapeutic approach for addressing ageing-related health problems?

Boosting NAD+ levels

What is attributed to DNA damage, dysfunction in cells, and exacerbation of age-related health issues?

A reduction in NAD+ levels Signup and view all the answers

What is the effect of inhibiting the activity of PARP on mitochondrial function and NAD+ levels?

It restores both mitochondrial function and NAD+ levels Signup and view all the answers

What are the noteworthy precursors that can enhance NAD+ levels?

NR, NA, and NMN Signup and view all the answers

What is the role of Nicotinamide Riboside (NR) in NAD+ biosynthesis?

It is a key player in NAD+ synthesis Signup and view all the answers

What is the consequence of NAD+ levels undergoing a notable decline in the ageing process?

Physiological deterioration Signup and view all the answers

What is the effect of overexpressing Hap4 gene in yeast and what is the underlying mechanism?

A 35% increase in lifespan in conventional glucose conditions due to a shift from fermentation to respiration, which increases the NAD+/NADH ratio. Signup and view all the answers

How does NADH dehydrogenase contribute to the increase in the NAD+/NADH ratio?

By oxidizing NADH, thereby increasing the NAD+ levels. Signup and view all the answers

What is the byproduct of NAD+ conversion by Sir2 and how does it affect Sir2 activity?

The byproduct is NAM (nicotinamide), which is a potent inhibitor of Sir2. Signup and view all the answers

What is the alternative method of NAD+ generation in yeast and what is the key enzyme involved?

The NAD+ salvage pathway, which involves the enzyme PNC1 (polycomb group repressor of nitric oxide controlling 1). Signup and view all the answers

What is the role of PNC1 in the NAD+ salvage pathway?

PNC1 deaminates nicotinamide (NAM) into nicotinic acid (NA), which is then converted into NAD+. Signup and view all the answers

What is the significance of the NAD+ salvage pathway in extending the lifespan of yeast?

The NAD+ salvage pathway helps to extend the lifespan of yeast by maintaining NAD+ levels, which is essential for Sir2 activity. Signup and view all the answers

What is the role of NR in NAD+ biosynthesis?

NR is a vitamin B3 precursor of NAD+ and is directly involved in NAD+ biosynthesis. Signup and view all the answers

What is the significance of NAD+ recycling in the context of Sir2 activity?

NAD+ recycling is essential for Sir2 activity, as Sir2 relies on the presence of NAD+ to perform deacetylase activity. Signup and view all the answers

What are the two NAD+ precursors that have potential dietary contributions to health?

Nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) Signup and view all the answers

What is the potential therapeutic benefit of boosting NAD+ levels in ageing and age-related diseases?

It may have therapeutic potential Signup and view all the answers

What role does NAD+ play in regulating cellular and metabolic signalling pathways?

It plays a crucial role Signup and view all the answers

How does calorie restriction extend lifespan in Saccharomyces cerevisiae, according to Anderson et al. (2003)?

Through nicotinamide and PNC1 Signup and view all the answers

What is the impact of genomic damage and ageing on stem cell function, according to Behrens et al. (2014)?

It has a negative impact Signup and view all the answers

What is the role of NAD+ metabolism in health and disease, according to Belenky et al. (2007)?

It plays a crucial role Signup and view all the answers

How do Nrt1 and Tna1-independent export of NAD+ precursor vitamins promote NAD+ homeostasis, according to Belenky et al. (2011)?

They allow engineering of vitamin production Signup and view all the answers

What is the benefit of using glucose as the main carbon source instead of dextrose in yeast experiments?

It allows for faster metabolism Signup and view all the answers

Study Notes

NAD+ Production and Pathways

NAD+ is produced through three main pathways: NAD+ salvage pathway, de novo biosynthesis pathway, and the Preiss-Handler pathway.
The NAD+ salvage pathway involves the enzyme PNC1, which deaminates nicotinamide (NAM) into nicotinic acid (NA), leading to the production of NMN, NAD+, and NAAD.

NAD+ and Ageing

A decline in NAD+ levels is a characteristic feature of ageing, associated with an increase in ROS accumulation.
Boosting NAD+ levels can mitigate metabolic alterations and age-related immune changes.
A reduction in NAD+ levels is attributed to DNA damage, dysfunction in cells, and exacerbation of age-related health issues.

Nicotinamide Riboside (NR) and NAD+ Biosynthesis

NR is a vitamin B3 precursor of NAD+ in the human diet and is directly involved in NAD+ biosynthesis.
NR supplementation can enhance NAD+ levels.
NR is a key player in NAD+ biosynthesis, which becomes pivotal when considering the multifaceted functions of NAD+ in cellular processes.

NAD+ and Cellular Processes

NAD+ is a cofactor for the deacetylation process mediated by Sir2.
The NAD+/NADH ratio affects cellular processes, with an increase in the ratio contributing to an increase in lifespan.
NAD+ conversion by Sir2 results in NAM production, a potent inhibitor of Sir2.

Other NAD+ Precursors

NA, NAM, and NMN are other noteworthy precursors that can enhance NAD+ levels.
Hap4 overexpression in yeast led to a 35% increase in lifespan in conventional glucose conditions.

Experimentation and Methodology

The initial cell density used for the growth curve may be reduced, and glucose should be used as the main carbon source instead of dextrose.
Adjusting the voltage and speed of gel electrophoresis runs, along with proper storage of PCR products, may improve the quality of the gel electrophoresis.

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Description

This quiz explores the three main pathways of NAD+ production in mammalian cells and its relation to ageing. It covers the decline of NAD+ levels and its effects on metabolic alterations and immune responses.