CHEM 4420 Metabolism: Lectures 1+2

Metabolism

What is the significance of 60/98/6?

What is the significance of 60/98/6?

60% of the body is composed of H2O; 98% of the body is composed of C, H, N, O, Ca2+. and P; AKA 6 elements

Creator of the metabolic maps

Nicholson

What explains the diversity of metabolic pathways?

Diversity in energy sources and sources of carbon

How many enzyme reactions encompass metabolism?

2200

How many pathways are involved in metabolism?

135

How many pathways involved in metabolism may lead to cancer?

12

How many tablespoons/grams of sugar are consumed over the course of the day by a human at rest?

250 g/20 tablespoons

Epigenome

Modifications made to the genome over time that does not change DNA’s sequence. Regulated by metabolism in that chromatin-modifying enzymes require metabolites.

Proteome

The entire set of proteins expressed at a given time under specific conditions. Consists of 250,000 metabolites. Influenced by metabolism

Glycome

The entire set of sugars free or part of more complex molecules within an organism. Influenced by metabolism

Lipidome

The entire set of lipids within cells. Influenced by metabolism

Transcriptome

The entire set of mRNA molecules expressed by an organism. Influenced by metabolism

Metabolome

Collection of all the metabolites produced by cells during metabolism.

What is reciprocal regulation?

When one process is highly activated, the opposite is inhibited. This is important for processes like anabolism and catabolism where a “futile cycle” would ensue without reciprocal regulation. Example: if glucose breakdown is highly active, glucose synthesis is inhibited.

What is a futile cycle in metabolism?

A metabolic futile cycle is one in which a precursor is converted into a product by a forward reaction and then re-synthesized to the precursor. In such a reaction, there is no net product accumulation, but energy (ATP) is used.

Which processes constitute the “backbone” of metabolism?

Glycolysis and gluconeogenesis; TCA (citric acid cycle) and ETS (electron transport chain)

The carbon source for autotrophs is:

CO2

The carbon source for heterotrophs is:

Organic C synthesized by phototrophs

Energy source for phototrophs:

Light

Energy source for chemotrophs:

Organic (glucose) and inorganic (i.e. sulfur) energy

Difference between aerobes and anaerobes:

Aerobes require oxygen for metabolism, while anaerobes cannot perform metabolism in the presence of oxygen

What are the two functions of metabolism?

To form energy to fund vital functions & to burn that energy to synthesize biomolecules

Catabolism is (exergonic/endergonic) and (oxidative/reductive)

Exergonic, oxidative

Anabolism is (exergonic/endergonic) and (oxidative/reductive)

Endergonic, reductive

What are energy-yielding nutrients used in catabolism?

Carbohydrates, fats, proteins

What are energy-poor end products produced by catabolism?

H2O, CO2, NH3

What are the precursor molecules for anabolism?

Amino acids, sugars, fatty acids, nitrogenous bases

What are the macromolecules produced through anabolism?

Proteins, polysaccharides, lipids, nucleic acids

Why are multi-enzyme complexes common?

Kinetically favorable to have multi-step reactions occurring in proximity to one another; H bonding between enzymes occurred over evolution to form multi-enzyme complexes

Where does the energy richness of ATP come from?

Its phosphoanhydride bonds- breaking these bonds yields 30 kJ/mole each (delta G = -30 kJ/mole)

Where does the energy richness of NADH come from?

Oxidation- the removal of H+ and 2e-

What are the three principle end products of catabolism?

Water, carbon dioxide, ammonia

What is the major energy production step of catabolism?

acetyl coA > citric acid cycle > oxidative phosphorylation

What is/are the minor energy production steps of catabolism?

Breakdown of large biomolecules to building block molecules > acetyl coA

What is an amphibolic pathway?

Pathways which serve in both catabolism and anabolism

What are two important endogenous pathways within catabolism?

Cannibalization of muscle tissue (in response to starvation), breakdown of stored fat (weight loss)

How has natural selection decreased the number of enzymes required for a catabolism/anabolism pathway?

Most reactions are bidirectional, close to equilibrium, and shared between the two pathways, while specific reactions are controlled and driven strongly in one direction and are specific to catabolism or anabolism.

In what form does NAD+ collect electrons to be shuttled to ATP production?

Hydride ions/reducing equivalents (H-) collected from oxidative catabolism

NAD+ is an electron () in ()

acceptor / oxidative catabolism

NADP+ is an electron () in ()

donor / reductive biosynthesis

RDI of carbohydrates

300 g/d

What are alternatives to dietary carbohydrates?

TAG and glycogen synthesis; ketone bodies from acetate

What are carbohydrates used for in anabolism?

Nucleotide, nucleic acid, glycoprotein and glycolipid biosynthesis

RDI of total fat

65 g/d

RDI of saturated fat

20 g/d

What is an amphibolic pathway?

A pathway with more reversible, non-regulated, shared steps than irreversible, regulated steps. Is more efficient

What purpose do fats serve?

Provide essential fatty acids that are components of membranes, they are important signal molecules

What is a potential consequence of not consuming enough linoleic acid (from, for example, chicken, potatoes, pasta, eggs, mayonnaise)?

Linoleic acid is a component of arachadonic acid; without it, prostaglandins (a clotting factor) cannot form which leads to clotting problems like hemophilia (EFA=essential fatty acid deficiency)

RDI of protein

50 g/d

What function does protein serve to a diet?

Nitrogen source; glucogenic AAs, ketogenic AAs (producing FAs and keto acids)

What is a consequence of high dietary nitrogen intake, from foods high in protein?

Kidney problems - nitrogen passes through the kidneys and is excreted as urea

RDI of fiber

38-50 g/d

Fiber contributions to energy production/catabolism and anabolism:

NONE

How do enzymes accelerate reactions by lowering the energy of activation?

Substrate binds to the enzyme, inducing a conformational change (induced fit model) by atomic contact and molecular interaction within the active site.

How many enzymes are in the human body?

3000-5000