Biochemistry of Carbon Cycle and Sugars

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Questions and Answers

What is the initial step in hepatic fructose metabolism?

Phosphorylation by fructokinase (correct)

Glycolysis regulation

Conversion to glucose

Oxidation of fructose

How does fructose bypass the major control point of glucose metabolism?

By entering at the triose phosphate level (correct)

By increasing ATP production

By activating phosphofructokinase

By decreasing citrate levels

Which enzyme's regulation is bypassed by fructose metabolism?

Phosphofructokinase (correct)

Pyruvate kinase

Fructokinase

Hexokinase

Which protein is responsible for encoding the different pyruvate kinase forms in the liver and red blood cells?

PKLR (B) Signup and view all the answers

What unique feature characterizes the erythrocyte PK mRNA compared to the liver PK mRNA?

Presence of exon 1 (C) Signup and view all the answers

What is one function of the glucose-sensing module in ChREBPα?

Inhibition in low glucose conditions (C) Signup and view all the answers

Which post-translational modifications are identified in ChREBPα?

Phosphorylation and acetylation (D) Signup and view all the answers

What role does fructose play in hepatic lipogenesis?

Unregulated source of acetyl-CoA (D) Signup and view all the answers

What is the primary function of glucose in the body?

To act as a primary energetic and synthetic fuel (A) Signup and view all the answers

What happens to fructose after ingestion?

It is rapidly cleared by intestines and liver (C) Signup and view all the answers

How does the loss of ChREBP affect metabolism?

It leads to metabolic dysfunction (D) Signup and view all the answers

What is the composition of sucrose?

Equal parts of glucose and fructose (A) Signup and view all the answers

What role do heterotrophs play in the carbon cycle?

They utilize plant-derived sugars for energy (D) Signup and view all the answers

Which of the following statements about fructose is incorrect?

Fructose is exclusively stored as glycogen (D) Signup and view all the answers

What relationship is indicated between sugar consumption and metabolic diseases?

High-sugar intake is linked to overweight and obesity (D) Signup and view all the answers

Why is the regulation of pyruvate kinase important?

It affects fat synthesis and energy regulation (B) Signup and view all the answers

What is the primary consequence of ChREBPβ being transcribed from alternative promoter 1b?

It generates a protein lacking critical domains such as NES and NLS. (A) Signup and view all the answers

Which chromatin state is characterized by preventing transcription factor binding?

Closed chromatin (A) Signup and view all the answers

How does ChREBP contribute to metabolic syndrome related to fatty liver disease?

By enhancing lipogenesis in insulin resistant states. (D) Signup and view all the answers

What effect does ChREBP inhibition have in ob/ob mice?

It results in the reversal of hepatic steatosis. (A) Signup and view all the answers

What is currently unknown regarding the relationship between ChREBPα and ChREBPβ?

Whether both isoforms bind to the ChoRE sequence. (A) Signup and view all the answers

What is the primary function of transcription factors in gene expression?

To guide RNA polymerase II to promoter regions. (A) Signup and view all the answers

What is the suggested contribution of de novo lipogenesis in patients with NAFLD?

It contributes around 25% of total liver lipids. (D) Signup and view all the answers

What is the role of chromatin state in transcriptional activation?

Only open chromatin directly enhances transcription factor activity. (A) Signup and view all the answers

What effect does the deficiency of carbohydrate response element-binding protein (ChREBP) have on lipogenesis?

It reduces lipogenesis. (D) Signup and view all the answers

Which parameter showed a significant change in plasma insulin levels between WT and ChREBP−/− mice?

Plasma insulin levels were significantly higher in ChREBP−/− mice. (A) Signup and view all the answers

What was the liver weight of ChREBP−/− mice on a high-starch diet?

1.63 g (C) Signup and view all the answers

How did plasma glucose levels differ between WT and ChREBP−/− mice on a standard rodent chow diet?

Plasma glucose levels were higher in ChREBP−/− mice. (B) Signup and view all the answers

Which outcome was significant regarding liver glycogen levels in WT versus ChREBP−/− mice?

ChREBP−/− mice had significantly higher liver glycogen levels. (D) Signup and view all the answers

In the measurements taken, which parameter did NOT show a significant difference when comparing WT and ChREBP−/− mice?

Muscle glycogen. (C) Signup and view all the answers

What change occurs in the plasma free fatty acid (FFA) levels due to ChREBP deficiency?

Plasma FFA levels decrease. (C) Signup and view all the answers

What was the expected outcome in the liver triglyceride levels of ChREBP−/− mice on a high-starch diet?

They showed significantly reduced liver triglyceride levels. (B) Signup and view all the answers

What effect does the absence of ChREBP have on glucose levels in mouse livers on a high-starch diet?

Increases glucose levels significantly (A) Signup and view all the answers

Which metabolite had the highest increase in concentration in ChREBP−/− mice compared to wild-type on a standard diet?

Glucose (D) Signup and view all the answers

What was the observed consequence of ChREBP deficiency in mice when they were unable to ingest sucrose?

Hypothermia and death (D) Signup and view all the answers

How did ChREBP deficiency affect pyruvate levels in wild-type and ChREBP−/− mice on a high-starch diet?

Decreased in ChREBP−/− mice (D) Signup and view all the answers

What does the ratio of pyruvate to PEP indicate in the context of ChREBP deficiency?

Reduced metabolic activity (A) Signup and view all the answers

Which metabolic function is primarily affected by ChREBP deficiency?

Glycolysis and lipogenesis (C) Signup and view all the answers

Which statement about glucose levels in mice fed a standard diet is accurate?

ChREBP−/− mice have higher glucose levels than wild-type mice (C) Signup and view all the answers

What is the impact of sucrose digestion on glucose and fructose generation in mice?

Sucrose generates both glucose and fructose (B) Signup and view all the answers

Study Notes

Carbon Cycle

Animals contribute to the carbon cycle by consuming sugars and releasing CO2.
Animals cannot synthesize their own sugars, they consume plant-derived sugars for energy and biosynthesis.

Sugars

Sucrose, the main sugar in plants, is comprised of equal parts glucose and fructose.
Glucose is the primary sugar in animals and is used for energy and synthesis in most tissues.
Fructose is found in small quantities, but it serves as a signal of sugar intake.

Fructose Metabolism

Fructose is rapidly cleared through the intestines and liver.
Fructose bypasses major control points in glucose metabolism, leading to an unregulated source of glycerol-3-phosphate and acetyl-CoA for lipid synthesis.

Pyruvate Kinase (PK)

Two forms of PK are encoded by the same gene (PKLR) with differences due to differential transcription.
The liver and red blood cell forms have different promoters:
- Red blood cell (R-PK) promoter is active only in erythrocytes due to a strong enhancer element.
- Liver (L-PK) promoter is active in liver and beta cells
Erythrocyte PK mRNA includes exon 1, while liver PK mRNA includes exon 2.
The R-PK protein is 574 amino acids long, L-PK protein is 543 amino acids.
PK is regulated by transcription and phosphorylation.

ChREBP

ChREBP is a transcription factor that regulates pathways for glycolysis and fat synthesis.
ChREBP has two isoforms: α and β
- ChREBPα regulates gene expression through binding to ChoRE sequences.
- ChREBP is activated by high carbohydrate diets.
- ChREBPβ is shorter and lacks domains needed for glucose sensing.
- ChREBPα regulates ChREBPβ.

Metabolic Dysfunction

ChREBP deficiency impairs glucose tolerance leading to hypothermia and death in mice.
Mice lacking ChREBP are unable to metabolize fructose.
ChREBP deficiency leads to lower levels of fatty acid synthesis.

NAFLD

Non-alcoholic fatty liver disease is linked to metabolic syndrome.
ChREBP and SREBP-1c activation contribute to increased lipogenesis in insulin-resistant states.
In obese mice, ChREBP inhibition through RNAi or genetic ablation reverses hepatic steatosis.

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Description

Explore the intricate interactions between animals and the carbon cycle, focusing on the metabolism of sugars like glucose and fructose. This quiz delves into the biochemical pathways and enzymatic functions, particularly highlighting pyruvate kinase. Test your knowledge on how these processes contribute to energy production and lipid synthesis.