---
title: "Biosyntheses and the Integrated Cell"
book: "University Biology — Year 1"
subject: biology
language: en
chapter: 16
exercises: 12
source: https://one-course.com/books/biology/3/en/chapter/16-biosyntheses-and-the-integrated-cell
---

# Chapter 16 — Biosyntheses and the Integrated Cell

At eight in the morning a liver is turning the sugar of breakfast into [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) and [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride); at three the next morning the same liver is making sugar out of the [amino acids](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-aminoacid) of muscle and pouring it into the blood for a brain that has eaten nothing for nine hours. Nothing in the [enzymes](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme) has changed; what has changed is which of them are switched on. The previous chapters took the [cell](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#def-b1-cell-unit-of-life-cell)’s molecules apart; this one puts them together — the syntheses of sugars, [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide), [fats](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride) and [amino acids](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-aminoacid) — and then asks how a [cell](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#def-b1-cell-unit-of-life-cell), and an [organism](https://one-course.com/books/biology/3/en/chapter/1-the-organism-a-system-in-interaction-with-its-environment#def-b1-organism-environment-organism), decide at each moment which pathways run. The answer is a small set of shared currencies, a few [enzymes](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme) at the crossroads, and hormones that tell every [cell](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#def-b1-cell-unit-of-life-cell) the state of the whole.

## 16.1 What a synthesis needs

**Proposition 16.1 (The three requirements of anabolism).**

Every biosynthesis needs *carbon skeletons*, drawn from a handful of intermediates of [glycolysis](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-glycolysis) and the [Krebs cycle](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-krebs); *reducing power*, supplied as [NADPH](#def-b1-biosyntheses-integration-ppp); and *energy*, supplied as [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp). Catabolism and anabolism therefore meet at the same crossroads — glucose-6-phosphate, triose phosphate, pyruvate, [acetyl-CoA](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-pdh), $\alpha$-ketoglutarate, oxaloacetate — but run on separate [enzymes](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme) at the irreversible steps, so that each direction can be switched independently, and they use separate [coenzymes](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme) for their electrons: NADH, kept oxidised, for taking electrons away in catabolism; [NADPH](#def-b1-biosyntheses-integration-ppp), kept reduced, for handing them over in synthesis.

**Definition 16.2 (The pentose phosphate pathway).**

The *pentose phosphate pathway* of the [cytosol](https://one-course.com/books/biology/3/en/chapter/6-functional-organization-of-the-eukaryotic-cell#def-b1-eukaryotic-cell-organelle) oxidises glucose-6-phosphate to ribulose-5-phosphate and $\mathrm{CO_2}$, reducing two $\mathrm{NADP^+}$ to NADPH; its non-oxidative branch then interconverts five-, four-, six- and seven-carbon sugar phosphates, so that the [cell](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#def-b1-cell-unit-of-life-cell) can make ribose-5-phosphate for [nucleotides](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-nucleotide) when it needs pentoses, NADPH when it needs reducing power ([fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride) synthesis, defence against oxidants), or both, and return the rest to [glycolysis](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-glycolysis). It is the main source of NADPH in animal [cells](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#def-b1-cell-unit-of-life-cell); in plants the chloroplast’s [light reactions](https://one-course.com/books/biology/3/en/chapter/14-photosynthesis-and-autotrophy#prop-b1-photosynthesis-lightreactions) supply NADPH by day.

![The crossroads of metabolism. Six hubs of the central pathways (blue) receive fuels and stores (orange) and supply every biosynthesis (green). Gluconeogenesis (red) runs the middle of the map upward.](https://one-course.com/images/onecourse/chapters/biology-3/b1-biosyntheses-integration/fig-5f7f33422484.svg)

*The crossroads of metabolism. Six hubs of the central pathways (blue) receive fuels and stores (orange) and supply every biosynthesis (green). [Gluconeogenesis](#def-b1-biosyntheses-integration-gluconeogenesis) (red) runs the middle of the map upward.*

## 16.2 Making glucose: gluconeogenesis

**Definition 16.3 (Gluconeogenesis).**

*Gluconeogenesis* makes glucose from [non-carbohydrate](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-monosaccharide) precursors — lactate, pyruvate, glycerol and the carbon skeletons of most [amino acids](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-aminoacid) — in the liver (and a little in the kidney). It runs [glycolysis](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-glycolysis) backward through its seven reversible steps and bypasses the three irreversible ones with different [enzymes](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme): pyruvate is carboxylated to oxaloacetate (in the [mitochondrion](https://one-course.com/books/biology/3/en/chapter/6-functional-organization-of-the-eukaryotic-cell#def-b1-eukaryotic-cell-mitochondrion), one [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp)) and decarboxylated to phosphoenolpyruvate (one GTP); fructose-1,6-bisphosphate is hydrolysed to fructose-6-phosphate; glucose-6-phosphate is hydrolysed to free glucose, which [leaves](https://one-course.com/books/biology/3/en/chapter/3-functional-organization-of-a-flowering-plant#def-b1-flowering-plant-organization-organs) the [cell](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#def-b1-cell-unit-of-life-cell). Per glucose: 6 [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) equivalents and 2 NADH, against the 2 [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) [glycolysis](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-glycolysis) yields — the price of running a downhill path uphill.

![Glycolysis and gluconeogenesis share seven reversible reactions and differ at three irreversible ones, each bypassed by a separate enzyme. Separate enzymes mean separate control: the liver can switch one direction on and the other off.](https://one-course.com/images/onecourse/chapters/biology-3/b1-biosyntheses-integration/fig-1927a30a2b89.svg)

*[Glycolysis](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-glycolysis) and [gluconeogenesis](#def-b1-biosyntheses-integration-gluconeogenesis) share seven reversible reactions and differ at three irreversible ones, each bypassed by a separate [enzyme](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme). Separate [enzymes](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme) mean separate control: the liver can switch one direction on and the other off.*

**Proposition 16.4 (What can and cannot become glucose).**

Lactate, glycerol, and the [amino acids](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-aminoacid) that yield pyruvate or Krebs-cycle intermediates (all but leucine and lysine) can be turned into glucose. [Fatty acids](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-fattyacid) cannot, in animals: their $\beta$-oxidation gives [acetyl-CoA](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-pdh), whose two carbons enter the cycle and leave as two $\mathrm{CO_2}$ before any oxaloacetate is gained, so there is no net route from [acetyl-CoA](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-pdh) to sugar. Plants, fungi and bacteria possess the *glyoxylate cycle*, a shortcut that skips the two decarboxylations and lets a germinating [oil](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride) seed turn its [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride) into the sugar its seedling needs. A starving mammal, by contrast, must make its glucose from [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide).

**Example 16.5 (The Cori cycle).**

A sprinting muscle ferments [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) to lactate, which enters the blood; the liver takes the lactate up, oxidises it to pyruvate, makes glucose from it at 6 [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) per glucose, and returns the glucose to the blood for the muscle to use again. The muscle has gained 2 [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) per glucose without oxygen and passed a bill of 6 to the liver, which pays it with oxygen at leisure: the “oxygen debt” of a sprint is repaid largely in the liver.

## 16.3 Storing: glycogen and fat

**Definition 16.6 (Glycogen synthesis).**

Glucose is stored as [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) by activating glucose-6-phosphate to *UDP-glucose* (one UTP), which *[glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) synthase* adds to the non-reducing ends of the existing tree; a *branching [enzyme](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme)* cuts and re-attaches short chains to make the $\alpha(1{\to}6)$ branches ([Chapter 10](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#ch-b1-carbohydrates)). Synthase and phosphorylase are regulated in opposite directions by the same signals: the phosphorylation that switches phosphorylase on switches synthase off, so the tree is never built and dismantled at once.

**Definition 16.7 (Fatty acid synthesis).**

[Fatty acids](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-fattyacid) are made in the [cytosol](https://one-course.com/books/biology/3/en/chapter/6-functional-organization-of-the-eukaryotic-cell#def-b1-eukaryotic-cell-organelle) from [acetyl-CoA](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-pdh) exported from the [mitochondrion](https://one-course.com/books/biology/3/en/chapter/6-functional-organization-of-the-eukaryotic-cell#def-b1-eukaryotic-cell-mitochondrion). *[Acetyl-CoA](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-pdh) carboxylase*, the regulated step, carboxylates it (one [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp)) to malonyl-CoA; *[fatty acid](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-fattyacid) synthase* then adds two carbons at a time from malonyl-CoA to a growing chain, reducing each addition with two [NADPH](#def-b1-biosyntheses-integration-ppp), until palmitate (C16) is released: 8 [acetyl-CoA](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-pdh), 7 [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) and 14 [NADPH](#def-b1-biosyntheses-integration-ppp) per palmitate. Elongation and desaturation in the [endoplasmic reticulum](https://one-course.com/books/biology/3/en/chapter/6-functional-organization-of-the-eukaryotic-cell#def-b1-eukaryotic-cell-endomembrane) make the other acids; esterification with glycerol-3-phosphate (from triose phosphate) makes [triglycerides](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride). The pathway is not $\beta$-oxidation reversed: different [enzymes](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme), a different compartment, malonyl-CoA instead of [acetyl-CoA](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-pdh), [NADPH](#def-b1-biosyntheses-integration-ppp) instead of $\mathrm{FADH_2}$ and NADH — and malonyl-CoA blocks the transport of [fatty acids](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-fattyacid) into the [mitochondrion](https://one-course.com/books/biology/3/en/chapter/6-functional-organization-of-the-eukaryotic-cell#def-b1-eukaryotic-cell-mitochondrion), so a [cell](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#def-b1-cell-unit-of-life-cell) does not make [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride) and burn it at the same time.

**Example 16.8 (Fat from sugar).**

A liver given more glucose than it can store as [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) makes [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride): glucose to pyruvate to [acetyl-CoA](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-pdh) (losing a third of the carbon as $\mathrm{CO_2}$ and gaining [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp)), [acetyl-CoA](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-pdh) to palmitate at the cost of that [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) and of [NADPH](#def-b1-biosyntheses-integration-ppp) from the [pentose phosphate pathway](#def-b1-biosyntheses-integration-ppp), palmitate to [triglyceride](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride) shipped to adipose [tissue](https://one-course.com/books/biology/3/en/chapter/4-animal-body-plans-and-tissues#def-b1-body-plans-tissues-tissue). Some $15\,\%$ of the sugar’s energy is lost in the conversion; the rest is stored nine times more compactly than [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) ([Chapter 9](https://one-course.com/books/biology/3/en/chapter/9-lipids#ch-b1-lipids)). The reverse — [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride) to sugar — is impossible.

## 16.4 Nitrogen: amino acids and nucleotides

**Definition 16.9 (Nitrogen assimilation, transamination).**

Ammonium enters organic matter almost entirely through *glutamate*: glutamate dehydrogenase adds it to $\alpha$-ketoglutarate, and glutamine synthetase adds a second to glutamate’s [side chain](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-aminoacid) (one [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp)), making glutamine. From these two donors, *transaminases* (aminotransferases, with a vitamin B$_6$ [coenzyme](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme)) move the amino group onto any $\alpha$-keto acid, building [amino acids](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-aminoacid) from the carbon skeletons of the central pathways: the glutamate family from $\alpha$-ketoglutarate, the aspartate family from oxaloacetate, alanine and serine from pyruvate and 3-phosphoglycerate. Plants and bacteria make all twenty; animals have lost the long pathways to nine of them, the *essential* [amino acids](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-aminoacid), and take them from food. The same transaminases, run backward, strip nitrogen from surplus [amino acids](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-aminoacid) for excretion as ammonia (fish), urea (mammals) or uric acid (birds, insects).

**Example 16.10 (Nucleotides).**

A [purine](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-nucleotide) ring is assembled on ribose-5-phosphate from glycine, aspartate, two glutamines, two one-carbon units and $\mathrm{CO_2}$, at the cost of six [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp); a [pyrimidine](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-nucleotide) from aspartate and carbamoyl phosphate. Deoxynucleotides are made from ribonucleotides by reducing the sugar, using [NADPH](#def-b1-biosyntheses-integration-ppp). A [cell](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#def-b1-cell-unit-of-life-cell) about to divide makes some $10^{10}$ [nucleotides](https://one-course.com/books/biology/3/en/chapter/11-nucleotides-and-nucleic-acids#def-b1-nucleic-acids-nucleotide) in an hour; the drugs that block these syntheses — methotrexate, 5-fluorouracil — stop dividing [cells](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#def-b1-cell-unit-of-life-cell) first, which is why they treat cancer.

## 16.5 The integrated mammal

**Proposition 16.11 (Fed and fasting).**

The [organs](https://one-course.com/books/biology/3/en/chapter/2-functional-organization-of-a-mammal#def-b1-mammal-organization-organ) share the work. After a meal, *insulin* from the pancreas tells the liver to store glucose as [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) and convert the surplus to [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride), the muscles to take up glucose and store [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide), the adipose [tissue](https://one-course.com/books/biology/3/en/chapter/4-animal-body-plans-and-tissues#def-b1-body-plans-tissues-tissue) to take up [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride); the blood glucose, risen to $8\,\mathrm{mmol}/\mathrm{L}$, returns to $5\,$ in two hours. Between meals, *glucagon* tells the liver to break its [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) down and, as it runs low, to make glucose from lactate, glycerol and [amino acids](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-aminoacid), and the adipose [tissue](https://one-course.com/books/biology/3/en/chapter/4-animal-body-plans-and-tissues#def-b1-body-plans-tissues-tissue) to release [fatty acids](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-fattyacid), which the muscles and the liver burn in place of glucose; the brain, which cannot burn [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride), keeps its $120\,\mathrm{g}$ of glucose a day. In a fast of days the liver turns [fatty acids](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-fattyacid) into *ketone bodies*, small acids the brain can use, and the demand for glucose — and for the [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) that makes it — falls by two thirds. The hormonal mechanisms belong to the Year 2 volume; the metabolic logic is this chapter’s.

![Blood glucose over a day. Each meal raises it for two hours while insulin drives storage; between meals and through the night, glucagon keeps it near 5\, mmol/ L from the liver’s glycogen and gluconeogenesis. The set point holds within a factor of two.](https://one-course.com/images/onecourse/chapters/biology-3/b1-biosyntheses-integration/fig-461fad0af042.svg)

*Blood glucose over a day. Each meal raises it for two hours while insulin drives storage; between meals and through the night, glucagon keeps it near $5\,\mathrm{mmol}/\mathrm{L}$ from the liver’s [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) and [gluconeogenesis](#def-b1-biosyntheses-integration-gluconeogenesis). The [set point](https://one-course.com/books/biology/3/en/chapter/1-the-organism-a-system-in-interaction-with-its-environment#def-b1-organism-environment-homeostasis) holds within a factor of two.*

![A liver lobule: plates of hepatocytes radiating from a central vein, bathed in blood from the gut. These cells store glycogen, make glucose, build fat and ketone bodies, and dispose of nitrogen — the metabolic clearing-house of the body.](https://one-course.com/images/onecourse/chapters/biology-3/b1-biosyntheses-integration/img-b92899ecb8d0.jpg)

*A liver lobule: plates of hepatocytes radiating from a central vein, bathed in blood from the gut. These [cells](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#def-b1-cell-unit-of-life-cell) store [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide), make glucose, build [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride) and ketone bodies, and dispose of nitrogen — the metabolic clearing-house of the body.*

**Method 16.12 (Reading a metabolic state).**

1. Ask which fuel is abundant: high glucose means storage ( [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) , then [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride) ); low glucose means mobilisation.
2. Follow the signals: insulin activates synthases and inactivates phosphorylase and lipase; glucagon does the reverse — mostly through phosphorylation of the same [enzymes](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme) ( [Chapter 13](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#ch-b1-enzymes) ).
3. Check the crossroads: [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) and citrate block PFK and open [gluconeogenesis](#def-b1-biosyntheses-integration-gluconeogenesis) ; AMP does the opposite; malonyl-CoA blocks [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride) burning while [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride) is being made; [acetyl-CoA](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-pdh) activates the carboxylase that starts [gluconeogenesis](#def-b1-biosyntheses-integration-gluconeogenesis) .
4. Assign the [organs](https://one-course.com/books/biology/3/en/chapter/2-functional-organization-of-a-mammal#def-b1-mammal-organization-organ) : liver (stores, makes and exports glucose; makes ketones and urea), muscle (stores [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) for itself, exports lactate and alanine), adipose [tissue](https://one-course.com/books/biology/3/en/chapter/4-animal-body-plans-and-tissues#def-b1-body-plans-tissues-tissue) (stores and releases [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride) ), brain (burns glucose, then ketones).

## 16.6 The integrated plant

**Proposition 16.13 (Source and sink).**

By day a [leaf](https://one-course.com/books/biology/3/en/chapter/3-functional-organization-of-a-flowering-plant#def-b1-flowering-plant-organization-organs)’s [chloroplasts](https://one-course.com/books/biology/3/en/chapter/6-functional-organization-of-the-eukaryotic-cell#def-b1-eukaryotic-cell-plastid) export triose phosphate to the [cytosol](https://one-course.com/books/biology/3/en/chapter/6-functional-organization-of-the-eukaryotic-cell#def-b1-eukaryotic-cell-organelle), where it is made into *sucrose* for export in the phloem ([Chapter 24](https://one-course.com/books/biology/3/en/chapter/24-plant-gas-exchange-and-sap-transport#ch-b1-plant-transport)) to the [roots](https://one-course.com/books/biology/3/en/chapter/3-functional-organization-of-a-flowering-plant#def-b1-flowering-plant-organization-organs), fruits and growing tips; what the phloem cannot take is kept in the chloroplast as *[starch](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide)*, a transient store, and mobilised at night to keep the sucrose flowing. Where a mammal’s liver decides between [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) and export by hormones, a [leaf](https://one-course.com/books/biology/3/en/chapter/3-functional-organization-of-a-flowering-plant#def-b1-flowering-plant-organization-organs) decides between [starch](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) and sucrose by the level of phosphate in the [cytosol](https://one-course.com/books/biology/3/en/chapter/6-functional-organization-of-the-eukaryotic-cell#def-b1-eukaryotic-cell-organelle), which controls the exporter of the chloroplast envelope. A plant regulates by the concentrations of its own metabolites, [organ](https://one-course.com/books/biology/3/en/chapter/2-functional-organization-of-a-mammal#def-b1-mammal-organization-organ) by [organ](https://one-course.com/books/biology/3/en/chapter/2-functional-organization-of-a-mammal#def-b1-mammal-organization-organ); the mammal adds a nervous and hormonal command over the whole.

![A variegated leaf before and after the iodine test: starch (blue-black) has been made only where chlorophyll was. The white regions, which imported sucrose from the green ones, made no starch of their own.](https://one-course.com/images/onecourse/chapters/biology-3/b1-biosyntheses-integration/img-c1aa6eb0498e.jpg)

*A variegated [leaf](https://one-course.com/books/biology/3/en/chapter/3-functional-organization-of-a-flowering-plant#def-b1-flowering-plant-organization-organs) before and after the iodine test: [starch](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) (blue-black) has been made only where [chlorophyll](https://one-course.com/books/biology/3/en/chapter/14-photosynthesis-and-autotrophy#def-b1-photosynthesis-pigments) was. The white regions, which imported sucrose from the green ones, made no [starch](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) of their own.*

**Example 16.14 (A night’s starch).**

A [leaf](https://one-course.com/books/biology/3/en/chapter/3-functional-organization-of-a-flowering-plant#def-b1-flowering-plant-organization-organs) sets aside as [starch](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) about half of what it fixes by day and degrades it at an almost constant rate through the night, so that the store runs out just before dawn: shorten the night artificially and [starch](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) is left over; lengthen it and the plant starves in the last hours. The rate is adjusted within the first hour of darkness to the size of the store and the expected length of the night — a computation done with [enzymes](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme) and a clock, in a [cell](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#def-b1-cell-unit-of-life-cell) with no brain.

## 16.7 Exercises

**Exercise 16.1 ★.**

Name the three things a biosynthesis needs and the pathway that supplies most of an animal [cell](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#def-b1-cell-unit-of-life-cell)’s [NADPH](#def-b1-biosyntheses-integration-ppp).

**Solution of Exercise 16.1.**

Carbon skeletons (from the central pathways), reducing power ([NADPH](#def-b1-biosyntheses-integration-ppp)), energy ([ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp)). The [pentose phosphate pathway](#def-b1-biosyntheses-integration-ppp).

**Exercise 16.2 ★.**

List the three irreversible steps of [glycolysis](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-glycolysis) and the [enzyme](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme) that bypasses each in [gluconeogenesis](#def-b1-biosyntheses-integration-gluconeogenesis).

**Solution of Exercise 16.2.**

Hexokinase, bypassed by glucose-6-phosphatase; phosphofructokinase, by fructose-1,6-bisphosphatase; pyruvate kinase, by pyruvate carboxylase plus PEP carboxykinase.

**Exercise 16.3 ★.**

From the blood-glucose figure, read the peak after breakfast, the time to return to $5\,\mathrm{mmol}/\mathrm{L}$, and the lowest overnight value.

**Solution of Exercise 16.3.**

Peak about $7.5\,\mathrm{mmol}/\mathrm{L}$ an hour after the meal; back to $5\,$ after about three hours; lowest about $4.5\,\mathrm{mmol}/\mathrm{L}$ before breakfast.

**Exercise 16.4 ★.**

Why can a germinating sunflower seed make sugar from its [oil](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride) and a starving human cannot?

**Solution of Exercise 16.4.**

The seed has the glyoxylate cycle, which turns two [acetyl-CoA](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-pdh) into one four-carbon acid without losing carbon as $\mathrm{CO_2}$, and from that acid makes sugar. Animals lack the two [enzymes](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme) of the shortcut: their [acetyl-CoA](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-pdh) enters the [Krebs cycle](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-krebs) and its two carbons leave as $\mathrm{CO_2}$ before any net oxaloacetate appears.

**Exercise 16.5 ★★.**

Compute the [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) cost of making one glucose from two lactate, and the net cost of one turn of the Cori cycle (muscle gains 2, liver spends 6). Who pays, and with what?

**Solution of Exercise 16.5.**

Six [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) equivalents (two carboxylations, two GTP, two [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) at the phosphoglycerate step) per glucose. Net per cycle: $2 - 6 = -4$ [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp). The liver pays, with oxygen, after the sprint — the muscle borrowed [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) it could not make aerobically in time.

**Exercise 16.6 ★★.**

One palmitate needs 8 [acetyl-CoA](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-pdh), 7 [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) and 14 [NADPH](#def-b1-biosyntheses-integration-ppp). How many glucose molecules must pass through [glycolysis](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-glycolysis) and pyruvate dehydrogenase to supply the [acetyl-CoA](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-pdh), and how many through the [pentose phosphate pathway](#def-b1-biosyntheses-integration-ppp) (2 [NADPH](#def-b1-biosyntheses-integration-ppp) each) to supply the [NADPH](#def-b1-biosyntheses-integration-ppp)?

**Solution of Exercise 16.6.**

Each glucose gives 2 [acetyl-CoA](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-pdh): 4 glucose. Each glucose through the oxidative branch gives 2 [NADPH](#def-b1-biosyntheses-integration-ppp): 7 glucose. Eleven glucoses for one palmitate — of which four provide carbon and seven provide electrons.

**Exercise 16.7 ★★.**

Explain why [fatty acid synthesis](#def-b1-biosyntheses-integration-fasynthesis) and $\beta$-oxidation use different [enzymes](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme), different compartments and different [coenzymes](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme), and how malonyl-CoA prevents them from running together.

**Solution of Exercise 16.7.**

Different [enzymes](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme) let each direction be switched on or off independently; different compartments ([cytosol](https://one-course.com/books/biology/3/en/chapter/6-functional-organization-of-the-eukaryotic-cell#def-b1-eukaryotic-cell-organelle) for synthesis, matrix for oxidation) separate the two pools of intermediates; [NADPH](#def-b1-biosyntheses-integration-ppp) is kept reduced for synthesis while [NAD](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-carriers) is kept oxidised for degradation, so each direction is thermodynamically favoured in its own place. Malonyl-CoA, the first committed intermediate of synthesis, inhibits the carnitine shuttle that carries [fatty acids](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-fattyacid) into the [mitochondrion](https://one-course.com/books/biology/3/en/chapter/6-functional-organization-of-the-eukaryotic-cell#def-b1-eukaryotic-cell-mitochondrion): while [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride) is being made, none is burned.

**Exercise 16.8 ★★.**

Write the [transamination](#def-b1-biosyntheses-integration-nitrogen) of alanine with $\alpha$-ketoglutarate and name the products. Which direction runs after a [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) meal, and which in a fast?

**Solution of Exercise 16.8.**

Alanine $+ \alpha$-ketoglutarate $\rightleftharpoons$ pyruvate $+$ [glutamate](#def-b1-biosyntheses-integration-nitrogen). After a [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) meal, surplus alanine gives its nitrogen to [glutamate](#def-b1-biosyntheses-integration-nitrogen) (rightward), for disposal as urea and its carbon for fuel or glucose. In a fast, muscle [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) is broken down and its amino groups collected onto pyruvate as alanine (leftward in muscle), shipped to the liver, and there converted back to pyruvate and glucose.

**Exercise 16.9 ★★.**

A patient lacks glucose-6-phosphatase. Predict the effects on blood glucose between meals, on the liver’s size, and on blood lactate, with reasons.

**Solution of Exercise 16.9.**

The liver cannot release free glucose: blood glucose falls dangerously between meals (hypoglycaemia). Glucose-6-phosphate accumulates and is diverted into [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide), which the liver cannot mobilise to the blood: the liver enlarges with [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide). The excess glucose-6-phosphate also runs down [glycolysis](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-glycolysis) to lactate, which rises in the blood.

**Exercise 16.10 ★★★.**

The brain needs $120\,\mathrm{g}$ of glucose a day and $1\,\mathrm{g}$ of [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) yields $0.55\,\mathrm{g}$ of glucose. Compute the [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) a fasting person would lose per day to feed the brain by [gluconeogenesis](#def-b1-biosyntheses-integration-gluconeogenesis) alone, and the muscle it represents ($20\,\%$ [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide)). Explain what ketone bodies change, if they cut the brain’s glucose need to $40\,\mathrm{g}$.

**Solution of Exercise 16.10.**

$120/0.55 = 218\,\mathrm{g}$ of [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) per day, about $1.1\,\mathrm{kg}$ of muscle. With ketone bodies, $40/0.55 = 73\,\mathrm{g}$ of [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide), $360\,\mathrm{g}$ of muscle: the loss falls by two thirds, and survival on the [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride) store is extended from weeks to months.

**Exercise 16.11 ★★★.**

Insulin activates [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) synthase and inactivates [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) phosphorylase; glucagon does the reverse. Explain why both cannot be active at once, what would happen if they were (compute the [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) wasted per cycle: one UTP to add a glucose, none to remove it), and what this “futile cycle” is used for in bumblebees warming their flight muscles.

**Solution of Exercise 16.11.**

The same phosphorylation cascade activates one and inactivates the other, so the signal that opens one valve shuts the other. Were both active, each glucose added (one UTP, equivalent to one [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp)) and removed (free) would cost one [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) per turn and produce nothing but heat. The bumblebee runs exactly such a cycle (on fructose-6-phosphate) in its flight muscles before take-off on a cold morning, burning [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) as a heater until the muscle is warm enough to fly.

**Exercise 16.12 ★★★.**

“A [cell](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#def-b1-cell-unit-of-life-cell) has no plan; it has valves.” Discuss in a paragraph: the [allosteric](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-allostery) and hormonal control of the crossroads [enzymes](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme), the role of separate [enzymes](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme) for opposite directions, and what emerges from them that looks like a plan.

**Solution of Exercise 16.12.**

Each crossroads [enzyme](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme) responds only to the molecules around it — [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp), AMP, citrate, [acetyl-CoA](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-pdh), a phosphate put on it by a kinase — and opens or shuts accordingly; separate [enzymes](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme) for the two directions mean that opening one direction can shut the other. No [enzyme](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme) knows about breakfast or the brain; yet the sum of these local responses is that the liver stores after a meal, releases at night, spares [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) in a fast: a coherent strategy, with no strategist. The “plan” is the wiring of the valves, chosen by selection, and the hormones that set many valves at once are what makes the [organism](https://one-course.com/books/biology/3/en/chapter/1-the-organism-a-system-in-interaction-with-its-environment#def-b1-organism-environment-organism) act as one.

## 16.8 Problem: Twenty-four Hours of a Human

**Problem 16.1.**

Weekend problem — a day without breakfast: the stores weighed, the brain fed, the protein counted and the fat mobilised, ending on the hours of fasting the liver’s glycogen can cover

A $70\,\mathrm{kg}$ adult expends $8.4\,\mathrm{MJ}$ a day ($100\,\mathrm{W}$ on average) and holds: liver [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) $100\,\mathrm{g}$, muscle [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) $400\,\mathrm{g}$, [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride) $12\,\mathrm{kg}$, [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) $10\,\mathrm{kg}$ (of which $6\,\mathrm{kg}$ in muscle). The brain uses $120\,\mathrm{g}$ of glucose a day ($5\,\mathrm{g}/\mathrm{h}$); the other glucose-dependent [tissues](https://one-course.com/books/biology/3/en/chapter/4-animal-body-plans-and-tissues#def-b1-body-plans-tissues-tissue) (red [cells](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#def-b1-cell-unit-of-life-cell), kidney medulla) $40\,\mathrm{g}$. Energy: [carbohydrate](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-monosaccharide) $17\,\mathrm{kJ}/\mathrm{g}$, [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride) $38\,\mathrm{kJ}/\mathrm{g}$, [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) $17\,\mathrm{kJ}/\mathrm{g}$; $1\,\mathrm{g}$ of [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) yields $0.55\,\mathrm{g}$ of glucose by [gluconeogenesis](#def-b1-biosyntheses-integration-gluconeogenesis); $1\,\mathrm{g}$ of [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride) yields $0.1\,\mathrm{g}$ of glucose (from its glycerol).

**Part I — The stores.**

1. Compute the energy held in each of the four stores, in megajoules, and the days of expenditure each represents.
2. Which store can supply glucose to the blood directly? Why not muscle [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) ?
3. Compute the total glucose the body needs per day for its glucose-dependent [tissues](https://one-course.com/books/biology/3/en/chapter/4-animal-body-plans-and-tissues#def-b1-body-plans-tissues-tissue) .
4. Compute the glucose in the blood itself ( $5\,\mathrm{mmol}/\mathrm{L}$ , $5\,\mathrm{L}$ , $180\,\mathrm{g}/\mathrm{mol}$ ) and the minutes it would feed the brain alone.
5. What fraction of the daily expenditure is the brain’s glucose?
6. After a meal, the liver’s [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) is full and the blood glucose still rising. Name the next fate of the glucose and the hormone that directs it.

**Part II — The night.** The last meal ends at 20:00; from then on the liver alone supplies the blood’s glucose.

7. At $160\,\mathrm{g}$ of glucose per day, what is the hourly demand of the glucose-dependent [tissues](https://one-course.com/books/biology/3/en/chapter/4-animal-body-plans-and-tissues#def-b1-body-plans-tissues-tissue) ?
8. How long does $100\,\mathrm{g}$ of liver [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) last at that rate, if nothing else supplies glucose?
9. In fact [gluconeogenesis](#def-b1-biosyntheses-integration-gluconeogenesis) supplies about a third of the glucose from the first hours. Recompute the duration of the [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) .
10. At what time in the morning does the liver’s [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) run out by each estimate?
11. The muscles, meanwhile, burn [fatty acids](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-fattyacid) . Compute the [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride) oxidised overnight ( $12\,\mathrm{h}$ ) if they account for $60\,\%$ of the resting expenditure and burn [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride) only.

**Part III — The next day, without eating.**

12. With the [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) gone, the $160\,\mathrm{g}$ of glucose must come from [gluconeogenesis](#def-b1-biosyntheses-integration-gluconeogenesis) . Compute the [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) needed per day, and the mass of muscle it represents.
13. Compute the [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) the liver spends making $160\,\mathrm{g}$ of glucose from pyruvate (6 [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) per glucose) and its energy at $50\,\mathrm{kJ}/\mathrm{mol}$ .
14. Compute the contribution of [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride) ’s glycerol: how much [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride) is oxidised per day if it covers all the non-glucose expenditure, and how much glucose its glycerol yields?
15. Recompute the [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) needed with the glycerol’s contribution subtracted.
16. At that rate, how many days until half the muscle is gone?
17. From the third day the liver makes ketone bodies and the brain takes two thirds of its energy from them; the glucose need falls to $40\,\mathrm{g}$ for the brain plus $40\,\mathrm{g}$ for the rest. Recompute the [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) loss per day and the days to lose half the muscle.
18. Compute the days the [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride) store lasts at $8.4\,\mathrm{MJ}$ a day (it falls to $6.5\,\mathrm{MJ}$ in prolonged fasting: recompute).
19. Explain why a fasting person dies of [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) loss before the [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride) is gone, and what ketone bodies delay.

**Part IV — The valves.**

20. Name the [enzyme](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme) of the liver that must be active at 03:00 and inactive at 09:00, and the one that must be the reverse, for [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) .
21. Name the signal (hormone) that sets them each way, and the chemical modification through which it acts.
22. A liver [cell](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#def-b1-cell-unit-of-life-cell) at 03:00 has high [acetyl-CoA](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-pdh) from [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride) oxidation. Name the [enzyme](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme) of [gluconeogenesis](#def-b1-biosyntheses-integration-gluconeogenesis) this activates and the [enzyme](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme) of [glycolysis](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-glycolysis) that [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) inhibits at the same time.
23. Explain why [gluconeogenesis](#def-b1-biosyntheses-integration-gluconeogenesis) and [glycolysis](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-glycolysis) , running at once in the same [cell](https://one-course.com/books/biology/3/en/chapter/5-the-cell-unit-of-life#def-b1-cell-unit-of-life-cell) , would only turn [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) into heat, and how the separate [enzymes](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme) at the three bypasses prevent it.
24. A diabetic without insulin has high blood glucose and yet the liver keeps making glucose and ketone bodies. Explain the paradox from the valves.
25. State the result: the hours of fasting the liver’s [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) covers (with and without [gluconeogenesis](#def-b1-biosyntheses-integration-gluconeogenesis) ), the daily [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) loss before and after the switch to ketone bodies, and the days the [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride) store lasts.

**Solution of Problem 16.1.**

**1.** Liver [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) $100\times 17 = 1.7\,\mathrm{MJ}$, 0.2 day; muscle [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) $6.8\,\mathrm{MJ}$, 0.8 day; [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride) $12\,000\times 38 =
456\,\mathrm{MJ}$, 54 days; [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) $170\,\mathrm{MJ}$, 20 days (never fully usable). **2.** Liver [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide): the liver has glucose-6-phosphatase. Muscle lacks it, so its [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) yields glucose-6-phosphate for its own [glycolysis](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-glycolysis) only. **3.** $120 + 40 = 160\,\mathrm{g}$ per day. **4.** $0.005\times 5\times 180 = 4.5\,\mathrm{g}$: at $5\,\mathrm{g}/\mathrm{h}$, about $54\,\mathrm{min}$. **5.** $120\times 17 = 2.0\,\mathrm{MJ}$, a quarter of the $8.4\,\mathrm{MJ}$. **6.** Conversion to [fatty acids](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-fattyacid) and [triglyceride](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride) in the liver, exported to adipose [tissue](https://one-course.com/books/biology/3/en/chapter/4-animal-body-plans-and-tissues#def-b1-body-plans-tissues-tissue); insulin. **7.** $160/24 = 6.7\,\mathrm{g}/\mathrm{h}$. **8.** $100/6.7 = 15\,\mathrm{h}$. **9.** [Glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) supplies two thirds, $4.4\,\mathrm{g}/\mathrm{h}$: $100/4.4 =
22\,\mathrm{h}$. **10.** 11:00 the next morning by the first estimate, 18:00 by the second — through the night in either case, with the margin depending on how early [gluconeogenesis](#def-b1-biosyntheses-integration-gluconeogenesis) takes over. **11.** Resting expenditure over $12\,\mathrm{h}$: $4.2\,\mathrm{MJ}$; $60\,\%$ is $2.5\,\mathrm{MJ}$; $2500/38 = 66\,\mathrm{g}$ of [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride). **12.** $160/0.55 = 290\,\mathrm{g}$ of [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide), i.e. $1.45\,\mathrm{kg}$ of muscle a day. **13.** $160/180 = 0.89\,\mathrm{mol}$ of glucose; at 6 [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) each that is $5.3\,\mathrm{mol}$ of [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp), and at $50\,\mathrm{kJ}/\mathrm{mol}$ about $265\,\mathrm{kJ}$ — some $3\,\%$ of the day’s $8.4\,\mathrm{MJ}$: making the glucose is cheap, and it is the carbon skeletons, not the energy, that the body is short of. **14.** Non-glucose expenditure $8.4 - 160\times 0.017 =
5.7\,\mathrm{MJ}$: $5700/38 = 150\,\mathrm{g}$ of [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride), whose glycerol gives $15\,\mathrm{g}$ of glucose. **15.** $(160 - 15)/0.55 = 264\,\mathrm{g}$ of [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide), $1.3\,\mathrm{kg}$ of muscle a day. **16.** $3\,\mathrm{kg}$ of muscle [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) at $264\,\mathrm{g}$ a day: about $11\,\mathrm{d}$. **17.** $(80 - 15)/0.55 = 118\,\mathrm{g}$ of [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide), $0.6\,\mathrm{kg}$ of muscle a day; half the muscle in $25\,\mathrm{d}$ — and in practice the loss falls further, to $20\text{ to }30\,\mathrm{g}$ a day, as the body economises. **18.** $456/8.4 = 54$ days; at $6.5\,\mathrm{MJ}$, 70 days. **19.** [Protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) is not a store but the machinery: losing a third of it (respiratory muscles, heart, immune [proteins](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide)) is fatal, and at $100\,\mathrm{g}$ a day or more that happens within weeks, while the [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride) would last two months. Ketone bodies let the brain run on [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride), cut the glucose demand and hence the [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) loss to a third, and stretch survival toward the limit set by the [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride). **20.** [Glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) phosphorylase active at 03:00, [glycogen](https://one-course.com/books/biology/3/en/chapter/10-carbohydrates#def-b1-carbohydrates-polysaccharide) synthase at 09:00. **21.** Glucagon (03:00) and insulin (09:00); phosphorylation of both [enzymes](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme) by a kinase cascade, reversed by a phosphatase. **22.** [Acetyl-CoA](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-pdh) activates pyruvate carboxylase; [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) (and citrate) inhibits phosphofructokinase. **23.** Glucose to pyruvate yields 2 [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp); pyruvate back to glucose costs 6: each round trip burns 4 [ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp) for no product. With distinct [enzymes](https://one-course.com/books/biology/3/en/chapter/13-enzymes-and-biochemical-catalysis#def-b1-enzymes-enzyme) at the three bypasses, the same signals ([ATP](https://one-course.com/books/biology/3/en/chapter/8-water-and-small-biomolecules#def-b1-water-small-molecules-atp), [acetyl-CoA](https://one-course.com/books/biology/3/en/chapter/15-cellular-respiration-and-fermentation#def-b1-respiration-fermentation-pdh), phosphorylation) activate one set and inhibit the other, so only one direction is open. **24.** Without insulin the valves are set as in fasting whatever the glucose: phosphorylase, [gluconeogenesis](#def-b1-biosyntheses-integration-gluconeogenesis) and lipolysis are on, synthesis is off, and the liver, “believing” the body starved, pours out glucose and ketones into blood already full of glucose that the insulin-dependent [tissues](https://one-course.com/books/biology/3/en/chapter/4-animal-body-plans-and-tissues#def-b1-body-plans-tissues-tissue) cannot take up. **25.** About $15\,\mathrm{h}$ without [gluconeogenesis](#def-b1-biosyntheses-integration-gluconeogenesis), $22\,\mathrm{h}$ with it — a night and a morning; [protein](https://one-course.com/books/biology/3/en/chapter/12-amino-acids-and-proteins#def-b1-proteins-peptide) loss about $260\,\mathrm{g}$ a day at first and $120\,\mathrm{g}$ (falling further) once ketone bodies feed the brain; the [fat](https://one-course.com/books/biology/3/en/chapter/9-lipids#def-b1-lipids-triglyceride) store lasts some $55\text{ to }70\,\mathrm{d}$.